Progesterone, cortisol, and their cognate synthetic agonists and antagonists seem to enter target cells freely and appear not to be significantly metabolized. A given ligand may bind to different receptors for example, P and RU bind to both PR and the glucocorticosteroid receptor [GR] , and a given receptor can bind multiple hormones e.
Upon binding of a ligand, transconformation of the receptor protein occurs. This molecular "reaction" is central to the mechanism of action of hormones and antihormones, and determines nuclear localization, binding to the hormone response element HRE of regulated genes, chromatin change, activation or inhibition of transcription, and possibly other activities. The GR and PR, like other steroid hormone receptors, form heterooligomeric, non-DNA binding, "nontransformed" 8S complexes that include receptor-associated proteins Baulieu et al.
Although their roles are not completely understood and remain controversial, certain relationships among these proteins are apparent. The binding of hsp90 by pHBI is not competitive with the binding of the immunosup pressants, which are inhibitors of the isomerase activity. The possible effect of pHBI binding to hsp90 on receptor function is, at present, unknown.
Hsp90 binds to the LBD apparently in a multipoint arrangement Pratt et al. In hspcontaining 8S receptor complexes, there are two molecules of hsp90 Radanyi et al. Hsp90, in the role of chaperone, maintains the structure of the GR LBD in the appropriate ligand-binding conformation and seems to protect non-ligand-bound steroid receptors from chemical or enzymatic attack.
It was also recently observed that hsp90 may competitively interfere with the binding of the HRE of an estrogen-regulated gene to the ER, and thus could modulate the process of transcription Redeuilh et al. Agonist binding to the LBD modifies the structure of the latter in such a way that it favors the release of hsp90 from the receptor, and therefore allows binding of the receptor to the HRE and interaction with transcription factors TFs engaged in the transcription machinery.
There may be a change of ligand affinity for the receptor even before dissociation of hsp90 Redeuilh et al. LBD modifications after binding of ligand are involved in TAF function, receptor dimerization, and probably chromatin changes. Whether hspreceptor complexes are formed in the cytoplasm, the nucleus, or both, and whether hsp90 binding plays a role in the transfer and shuttling of the receptor between the two compartments, are not yet clear. Nuclear binding to the HRE and recycling of the receptor depend upon these movements.
The hormone-dependent homodimerization of receptors is important for their binding to the two halves of the imperfect palindromic HRE. They are ligand activated following receptor binding and are most often physically situated in the 5'-promoter region of hormone-regulated genes. Schematically, HREs may be seen as allowing the receptor dimer to be placed in the appropriate position for interaction with other TFs, which bind to their specific DNA sequences and are involved in the function of RNA polymerase, the enzyme that is ultimately operational in gene transcription.
There are proteins that appear functionally to link receptors and TFs, and are sometimes designated as transcription intermediary factors TIFs. These factors are necessary when the HREs are situated far away, in molecular terms, from the transcription initiation site. The receptor domains involved in TAFs are described later. RU may interfere with several of the steps indicated in Table B1. RU has high affinity for the hPR and the hGR as 4-hydroxytamoxifen has for the hER , weak affinity for the human androgen receptor, and no affinity for the ER and the MR thus being a useful compound for the study of this last receptor in the presence of GR, since GR and MR share many high-affinity hormone ligands and GR is found in almost all cells.
Receptor transconformation is a conformational change in the receptor that occurs after ligand binding. Transconformation may take place before dissociation of hsp90 from the 8S complexes Allan, a,b , as observed with the 8S ER Redeuilh, b , and thus precedes DNA binding and activation of the transcription function. Selective, hormone-, or antihormone-related transconformation has been physically suggested by several observations:. A difference in the receptor structure when bound to hormone versus antihormone has also been observed with antiestrogen-ER complexes Sabbah et al.
In contrast to R PR R is a synthetic progestin agonist of the 4S sedimentation coefficient , RU PR forms 6S entities in salt-containing gradient centrifugation experiments Mullick and Katzenellenbogen, ; Renoir et al. It is not clear whether this form is transconformed monomeric PR, homodimeric PR, or a heterodimer of one molecule of PR plus another protein, perhaps hsp Conversely, if the corresponding Gly of the hPR is transformed into cysteine, RU no longer binds.
A truncated PR molecule minus the 42 C-terminal amino acids does not bind progestin agonists but does bind RU , which remarkably becomes an agonist Vegeto et al. Moreover, from these results, it has been postulated that the C-terminal region of the receptor could act as an inhibitor of TAF1 in the absence of ligand or when bound to RU , with the negative function being released in the presence of an agonist Vegeto et al.
Transconformation of the LBD is probably involved in the modulation of hsp90 interaction with the receptor, and the in vitro stabilization of hspcontaining 8S complexes after RU binding has been demonstrated for RU bound GR Groyer et al. In intact cellular systems, this stabilization has also been observed by several workers Rajpert et al. Stabilization of RU by the heterooligomeric, non-DNA-binding form, of the glucocorticosteroid receptor in KCI-containing medium, as compared to the transformation effect more It should be acknowledged, however, that the situation is complex; nuclear retention of GR may vary depending on the phase of the cell cycle Hsu et al.
Also on this point, a number of studies in intact cells have strongly suggested that RU receptor complexes move to the nucleus and then bind to HREs see ''Binding to DNA". The matter is still controversial, and we cannot definitively state whether RU receptor stabilization plays a significant role in antihormone action.
The extent of receptor dimerization frequently correlates with the specific DNA-binding activity of receptors. If the PRE palindrome is imperfect, as it is naturally, formation of a heterodimer is possible De Marzo et al. Therefore, dimerization is dependent not only on ligand-receptor interaction but also on receptor-DNA interaction. Heterodimerization including one RU bound PR unit may be involved in the strong antihormonal activity of RU via the negative effect of the RU subunit on the heterodimer function.
These results, in which the receptor is transformed and dissociated from hsp90, are consistent with the agonistic effects of RU observed in some cell systems Meyer et al. The term "agonistic" implies that the receptor can bind to appropriate specific DNA. In the case of an antihormonal effect, indirect but suggestive evidence has been obtained by competition of a constitutively active truncated form of progesterone receptor with RU PR complexes Guiochon-Mantel et al. It has been suggested that the onaprisone-receptor complex does not have the ability to bind to HREs Klein-Hitpass et al.
This would define a new type of antisteroid "type one" for Klein-Hitpass, "type two" for Bocquel et al. This could be due to the lack of formation of a stable receptor dimer, but it has been recently disproved by Bocquel et al. In vitro, onapristone, in contrast to RU Schweizer-Groyer et al. Hyperphosphorylation of the receptor that is observed under agonist or RU action is not observed using onapristone, again consistent with the hypothesis that a DNA-dependent protein kinase activity is involved Bocquel et al.
Moreover, these experimental differences between onapristone and other antiprogestins, particularly RU , may be ascribed to its low affinity for PR Delabre et al. The most likely explanation is that the chromatin modification induced by receptor transconformation after agonist binding does not occur after RU binding. Activation of gene transcription is regarded as the major mode of action of steroid hormones, mediated by two transcription activation functions of the receptor Evans, ; Lees et al. TAF1 is situated in the N-terminal portion of the receptor molecule, is not hormone dependent, and can be regulated by cell-specific factors.
TAF2 is hormone dependent, activated by agonist binding, and inhibited by antagonists, as demonstrated with tamoxifen derivatives for the ER Webster et al. When TAF2 is inhibited, TAF1 may still operate differently depending on the cell type, and thus an antihormone may show some agonistic activity following binding of the receptor to DNA. This is true with RU and theoretically should never be found with non-DNA-binding antagonists if they exist.
The type of receptor may itself influence the result, with a probable role for the highly variable N-terminal domains. TAF1 may also be controlled by an inactivation factor similar to that reported in yeast McDonnell et al. An example of this is the modifying effect on antiprogestin action of another cAMP-dependent gene Sartorius et al.
The expression of the receptor itself may change under the effect of its own ligand, as demonstrated for the down-regulation of the PR by progesterone Milgrom et al. However, the effect of RU on receptor down-regulation cannot be systematized, not being observed in certain cases Sheridan et al. In conclusion, as would be predicted, everything depends on the complex formed by the ligand and the receptor, which is then transconformed after binding. It is important to note that genetic variation may abrogate the response to RU Perhaps this is the case in the 1 percent of failures in abortion see later , or in cancers if there are mutations such as those cited above.
The net result may be to increase or decrease gene transcription, and depends in part on specific HREs and TF s. Antiprogestins are remarkable tools for dissecting complex cellular networks. In addition to more discoveries in cell biology, the study of these networks should lead to improved use of RU and the development of novel molecules. How lucky we were not to know of this complexity before testing RU , which worked so well on the basis of a "simple" hypothesis!
Herrmann et al. The activity of RU has been studied in many progesterone-responsive reproductive systems Baulieu, a; Brodgen et al. For example, studies in the uterus, endometrium, myometrium, and cervical tissue directly relate to the use of RU in fertility control. In the human myometrium Table B1. There is a decrease of prostacyclin release Lobaccaro-Henri et al.
In the rat, the increase of PG levels may not precede the stimulation of uterine contractility Arkaravichien and Kendle, Some hormonal components of RU activity are difficult to classify. For instance, RU and onapristone display an ER-independent antiestrogenic activity in the endometrium Van Uem et al. This seems paradoxical since RU and onapristone do not bind to the ER, and there is a PR-dependent increase of ER levels indicated by both hormone binding and immunocytochemistry Haluska et al.
In pregnancy, RU inhibits the production of human chorionic gonadotropin hCG and prolactin in cultured syncytiotrophoblast cells and explants Herrmann et al. It decreases a marker of ER function, p29, in the placenta and the decidua Rivera et al. RU also increases the natural killer activity of lymphocytes Hansen et al. In rats, it augments the interstitial collagenase activity of the cervix Ikuta et al. RU can inhibit the ovulation process Loutradis et al. Changes in the hypothalamus-pituitary-gonadal system have been reported.
Sexual behavior can be modified by the antiprogestin effect of RU Brown and Blaustein, ; Pleim, In breast cancer cells, RU inhibits P-induced transcriptional activity, which leads to the synthesis of fatty acid synthetase but, surprisingly, it stabilizes the mRNA of this enzyme Chalbos et al. Agonistic effects of RU have been observed in vivo in the uterus e. View in own window. Thus, administration of RU may produce effects in different directions, which have to be studied separately in each tissue. However, to provoke abortion or trigger labor, the effects on the decidua, endometrium, cervix, and even the trophoblast combine to make RU a very efficient agent for the termination of pregnancy.
On the basis of animal experiments, we expected RU to meet the recognized need for an efficient medical means of early abortion, to be safer than a surgical technique, and to be relatively convenient and cheap no anesthesia, no operating room. To develop a medical method of abortion was a must in terms of women's health and potentially a step toward more privacy for those having taken the difficult decision of pregnancy termination.
Since the postulated mechanism of action Figure B1. Physiopharmacological mechanism of action of RU on the implanted blastocyst. Temporally, the antiprogesterone effect of RU comes first, and then an increase in PG concentration and action, followed by a decrease in hCG-sustained corpus luteum more The results were so striking that RU immediately got the nickname "abortion pill," despite the many other potential medical uses already predicted when the compound was announced they progressively became reality.
However, after the study by Bygdeman and Swahn Table B1. The largest study Ulmann et al. However, three myocardial infarctions, including one fatal case a medical mistake occurred when sulprostone was injected into a woman at great risk , were recorded after more than 60, cases. Sulprostone for intramuscular administration has since been withdrawn from the market in France. Coincidentally, the death of a patient having received intramuscular Sulprostone was reported at the same time as the first trial of RU plus orally active misoprostol a PGE 1 derivative was published Aubeny and Baulieu, We had hoped to use a safer prostaglandin misoprostol has a record of millions of users for the prevention and treatment of gastrointestinal ulcers in individuals often at greater cardiovascular risk than normal pregnant women.
It was also obvious that an orally effective, already available, cheap, and easy to store prostaglandin had the potential to be an important improvement, since it could allow a more convenient and private method of abortion. Most results Peyron et al. Besides safety, this regimen was well tolerated—uterine cramps were minimized. Details and discussion of the method are found elsewhere Peyron et al. Currently in France, a woman suspecting an unwanted pregnancy sees a physician at a first visit, and after a delay for reflection she may return second visit to take the RU pills. Two days later, she makes a third visit to the center to receive prostaglandin and then stays for four hours.
A control follow-up visit the fourth should take place 10 to 15 days later. This method is currently not applicable to heavy smokers and women older than All these precautions need to be reexamined, however, and most appear to be dispensable. In the future, it is hoped that a woman would consult her physician as early as possible in the case of missed menses and then receive, if this is her choice, RU from a medically competent person who will have examined her.
She will then take home the misoprostol pills for self-administration 48 hours later and return for a checkup in approximately two weeks. Although RU and misoprostol are safe drugs, pregnancy itself is a risk for women, no matter whether they wish to interrupt or continue it e. Maintaining contact with a physician is mandatory, and there should be an appropriate permanent connection with a competent medical center in case of complications. Although it may be sufficient in the vast majority of cases for physicians preferably gyne cologists to see patients privately, it has been reported that many women prefer to be treated in a group at a medical center Thong et al.
Research should be conducted to define the best ways to administer the medications under specific conditions. It is certain that requirements for skilled personnel and sterile surgical facilities will be decreased El-Refaey et al. The mechanism of action of prostaglandin at low doses indicates that the effect takes place only when progesterone activity has been much decreased by the antisteroid—after more than 24 hours. Whether a combination of RU and prostaglandin to be administered simultaneously will become available is not predictable, since no technology for delayed prostaglandin release is in sight.
Application of this method in developing countries is necessarily more difficult, and local conditions must be considered, including the availability of medical facilities and personnel, cultural traditions bleeding for several days may be a problem , and the social context. However, women have the right to obtain medical assistance in case of suspected pregnancy, to have the choice to decide to abort, and if so, also to have the choice of either a surgical or a medical method. Whether in developing or industrialized countries, we ought to offer a complete medical choice to women.
Even the RU plus misoprostol method may be imperfectly applied for a period of time in certain countries, but it can only be a definite improvement of the present situation. It has also been successfully used for missed abortions and anembryonic pregnancies El-Refaey et al. Whether RU plus misoprostol may be used to compensate for the lack of access to family planning and to health facilities is another question.
Generally speaking, the best solution is to make available widely accepted and very efficient methods of contraception. The effects of progesterone, essentially on the decidua implantation , the myometrium calming effect , and LH secretion depressed with lack of ovulation , are observed throughout the course of pregnancy; thus, it is not surprising that an antiprogesterone is potentially useful for pregnancy interruption and labor induction.
In France, voluntary pregnancy interruption is legally permitted until 12 weeks of amenorrhea. When women have passed beyond the current legal limit for RU plus misoprostol treatment seven weeks , vacuum aspiration is performed. This can be greatly facilitated by RU taken 24 to 48 hours before the procedure—preoperative cervical preparation ripening Henshaw and Templeton, ; Urquhart and Templeton, A dose of — mg of RU decreases the force required to dilate the cervix and has significantly fewer side effects than gemeprost vaginal pessary.
In therapeutic second- and third-trimester abortions, RU is most often used before the administration of prostaglandin, so that the dose of prostaglandins can be decreased, while pain and other side effects are reduced and expulsion is accelerated Rodger and Baird, RU also decreases the waiting time, and thus the pain and psychological suffering, in cases of a fetal demise Cabrol et al.
A decrease of progesterone activity occurs during parturition, but its precise role in successful delivery is unclear, particularly in primates including humans where it does not seem to be the primary event. In rats, RU can synchronize delivery Bosc et al. In rhesus macaques near term, RU provokes changes of prostaglandins and of the cervical status, but these modifications do not follow the same orderly sequence as those found during spontaneous delivery Haluska et al. It is not known if RU increases gap junctions between myometrial cells in women as it does in rats Garfield et al.
RU has been tested in women at term who require labor induction for various medical indications such as post-term pregnancy and preeclampsia. When compared to placebo controls, the number of spontaneous deliveries is significantly increased; the amount of oxytocin, if required, is much lower; and the time to induce labor is shortened by RU Frydman et al. No undesirable incident, in mothers and newborns, was observed with the dose used two times, mg each , similar to observations made in monkey studies Wolf, b.
In summary, RU appears to be safe for inducing labor when continuation of pregnancy is a risk for the fetus, the mother, or both. Systematic studies should now follow the development of babies born after RU treatment, since it is known that in primates, RU passes from mother to fetus during pregnancy Wolf et al. The effects of neonatal and even embryonic Wolf et al. Until the absolute safety of antiprogestins is demonstrated in cases where there is a medical indication for labor induction, its use for convenience should be forbidden. The previous considerations apply to pregnancy that has been demonstrated by missed menses and a positive pregnancy test, a situation clear to all women.
Before this well-defined state, even if the biological steps are known, there is still confusion and ignorance as to when pregnancy begins. As a result, the vocabulary used to define the possible antihormonal interventions during the processes establishing pregnancy needs to be clarified. If menses does not occur and a pregnancy test is positive, interruption is clearly defined as abortion.
However, vacuum aspiration practiced very early, within approximately two weeks of menses delay, is called ''menses regulation" e. On the other hand, any maneuver inhibiting fertilization is called contraception, for contra conception. The word conception is generally understood as fertilization; this is wrong etymologically, since concipire Latin means to retain originally retain sperm and mother blood in the uterus to make the child. Contraception is, therefore, commonly understood as a method to preclude fertilization, for instance, by suppression of ovulation or preventing sperm from reaching the ovum.
However, physicians also designate as contraceptives methods that are applied before implantation is completed. They argue that a fertilized ovum that is not implanted after in vitro fertilization does not define a pregnancy. In fact, the available pregnancy tests are based on the measurement of human chorionic gonadotropin, produced by the embryonic chorion, which passes into the woman's blood and occurs only after implantation has been initiated. Intrauterine devices IUDs can be defined as "contraceptive" tools because they work, in part, as anti-implantation agents.
The word post-coital contraception is also largely accepted and applies to a possibly fertilized ovum. Note also that the process of implantation is not instantaneous and takes several days during the last week of the fertile menstrual cycle, just before the time at which menses would occur. Coincidentally, the development of the embryo is characterized by the streak a marker indicating that an individual embryo has been formed, and there is no further risk of twins , which should occur at approximately the same time—about 15 days after fertilization.
Before that time, not only may genetic abnormalities or defects of implantation stop the process leading to pregnancy, but the very definition of a single potential person cannot be rigorously applied. In short, during the period between fertilization and the time at which menses should occur, interrupting methods are contragestive, differing from both abortion and contraception as defined above, and not hiding the fact that they oppose pregnancy.
In summary, contragestion includes all treatments that operate over a period of approximately four weeks postfertilization. Such treatments include RU , other "morning-after" pills, early vacuum aspiration, and IUDs as well as a potentially anti-hCG "vaccine". Recent studies have shown that RU single mg dose given to women after unprotected intercourse within the preceding 72 hours is highly efficient at preventing pregnancy Glasier et al. It is at least as effective as the high-dose combined estrogen and progestin preparations, and better tolerated by the women.
Research needs to be pursued in order to determine the appropriate dose, and whether the administration can be repeated, how many times, and for how long, a possibility that appears rather remote because of probable changes in menstrual cyclicity. The administration of or mg of RU , once or twice, two days before the expected menses, results in about a 20 percent failure in terms of initiating pregnancy.
Since the probability of being pregnant is about 20 percent in normal couples, this leaves only 4 percent of women being pregnant to be secondarily interrupted by other means Dubois et al. The method is well tolerated and may be improved with the associated use of misoprostol. Giving RU approximately two days before the expected day of menses over several months has not been successful Van Santen and Haspels, , the main reason being the irregularity of cycles, often due to the retardation of ovulation that is induced by the compound.
In order to overcome this difficulty, a trial using a lower dose of RU plus misoprostol, two days before and on the expected day of menses, has been undertaken. Progesterone acts on the endometrium to prepare for implantation. This has been studied in detail in the ovariectomized rhesus monkey by analyzing the decidual transformation and the epithelial plaque formed in response to deciduogenic stimulus Ghosh and Sengupta, An immunocytochemical study, assessing an endometrial secretory glycan sialo-oligosaccharide , has shown that its production is P dependent Graham et al.
Moreover, experiments in rabbits have shown that endometrial receptivity and embryo implantation can be modified by antiprogestins Hegele-Hartung et al. Treatment with mg of RU was performed on women at the 2-day post-LH stage who had had unprotected intercourse at least once during the period three days before to one day after ovulation. Over cycles, only one pregnancy occurred Gemzell-Danielson et al. The main drawback of the method is the timing of the treatment. To use the method monthly, ovulation detection needs to become routine in the future.
Doses of 10 mg of RU administered on days 5 and 8 after the LH surge do not provoke hormonal change but do interrupt endometrial maturation with lowered PR levels Greene et al. The provisional name "endometrial contraception" is given to the continuous exposure to a very low dose of RU This may modify the genital tract in such a way that implantation and possibly fertilization do not occur, while ovulation and the pattern of estrogen and progesterone secretion are unchanged, and adrenal function is unmodified.
Daily use in cycling guinea pig prevents implantation Batista et al. After administration of a low dose of RU In a similar study, RU 1 mg given daily to nine women delayed ovulation and endometrial maturation, with a reduced peak of placental protein 14 a glycoprotein marker for endometrium function Batista et al. Currently, studies are being organized using even lower daily doses of RU given to women.
An international comparative study will define the highest dose of RU actually very small that can be administered chronically to women without perturbation of the cycle. Furthermore, this dose will be tested for contraceptive efficacy. Initially, these studies will be conducted using RU containing pills administered daily. Secondarily, in case of success, we will move from pills to injectable microspheres that will allow the slow release of RU for several months. A number of observations demonstrate that P contributes to ovulation Collins and Hodgen, ; Liu et al.
The administration of RU during the follicular phase delays or suppresses ovulation. This may designate a new method of estrogen-free contraception. The main problem is to find an effective, well-tolerated dose. Using 5 mg of RU per day may block ovulation without causing a change in adrenal function Ledger et al. The sequential administration of RU and progestin to maintain menstrual bleeding has been proposed Croxatto and Salvatierra, We submit that this method with ovulation suppression will be more difficult to implement relative to continuous administration of a very low dose. However, any contraceptive method should be studied carefully for a rather long period of time to delineate the possibility of side effects for the women and alteration of the embryo in case of failure Wu, Progesterone increases calcium uptake by human sperm and favors the acrosomal reaction Baldi et al.
There is likely to be a membrane receptor mediating its action as in the progesterone-induced reinitiation of meiosis in Xenopus laevis oocytes Blondeau and Baulieu, However, in sperm, as well as in oocytes, RU may not act as an antiprogestin at the membrane-receptor level.
A preliminary report C. Puri, patent preview WO A1, of a contraceptive effect of RU in monkeys with a decrease of sperm counts has not, to my current knowledge, yet been confirmed. RU can suppress ovulation, and inhibit the mitotic action of estrogens in the monkey endometrium. These effects suggest that the compound may be useful for the treatment of endometriosis Kettel et al. As expected, in women, RU suppressed ovulation and menstrual cycle, and brought about an increase of LH with augmented pulse amplitude but not frequency , adrenocorticotropic hormone ACTH , and cortisol.
Pain was decreased, but there was no decrease in the extent of the disease corroborating observations in the rat by Tjaden et al. Murphy and coworkers have reported a 50 percent regression of uterine leiomyomas by daily administration of 50 mg of RU for several weeks. This may be due principally to induced anovulation. Modulation of uterine growth factors and insulin-like growth factor IGF -binding proteins may also be involved Murphy et al. The treatment provokes an increase of LH, but not of FSH, and of dehydroepiandrosterone sulfate, androstenedione, testosterone, and cortisol, while estrogens, progesterone, sex steroid-binding plasma protein SBP , thyroid-stimulating hormone TSH , and prolactin PRL are unchanged, compared to original early follicular phase levels.
In myometrial and leiomyomatous tissue, PR but not ER immunoreactivity is decreased. Amenorrhea and anovulation are constant. The significant decrease of PR levels may indicate a direct antiprogesterone effect; however, an alteration in ER function cannot be excluded, as discussed above. The human papillomavirus type 16, episomal expression in ectocervical cells cervical keratinocytes is stimulated by glucocorticosteroids and progesterone Mittal et al.
Since RU may inhibit this induction in premalignant cervical lesions, do such data have application in human pathology?
Full text of "Catalogue de la bibliothèque de Ricardo Heredia, comte de Benahavis"
Breast cancer in women is multifaceted and probably corresponds to several distinct pathophysiological and molecular processes see recent review by Horwitz, Human carcinomas occur at different ages before and after menopause ; tumors in different animal species can be provoked by carcinogens and viruses; and various cultured cancer cells demonstrate different responses to progesterone. For example, in the classical experiments of Huggins and Yang , progesterone was shown to be a promoter of DMBA-induced mammary tumors in the rat, while in contrast, a high dose of progestins is therapeutically useful in advanced cases of breast tumors in women Pronzato et al.
RU inhibits the growth of breast cancer cells in a PR-dependent manner Bardon et al. Interestingly, one may demonstrate 1 antiprogestin-, progesterone-, and PR-dependent effects of RU , lilopristone, and onapristone Michna et al. This has been observed in human tumor cells either cultured in vitro or transplanted into appropriate animals.
Clinically, only three studies concerning the effects of RU and tumor development have been published Maudelonde et al.
B1. 1993: RU 486—A Decade on Today and Tomorrow
Trials are currently being performed in Canada and France. Indeed, clinical studies should concern pre- as well as postmenopausal women, and should analyze the mitotic pattern and the steroid and growth factor receptors under simultaneous or successive association of various antiprogestins with tamoxifen. Studies must also include compounds that may have less antiglucocorticosteroid activity, the association of antisteroid with antisteroidogenic drugs, and detailed molecular genetic description of PR mutations.
Breast cancer studies may unveil original PR-dependent control mechanisms of the cell cycle—in particular, hormone-independent, receptor-dependent or -independent effects as already suggested for tamoxifen. In other words, just as for antiestrogens Bardon et al. The growth of other cancers may be decreased by RU treatment.
Meningiomas are common tumors, generally benign and slow growing, that can threaten brain function—or even life—if they are not surgically removed. More frequent in women, meningioma growth is accelerated during pregnancy. Most meningiomas contain PR and often little or no ER , and it has been suggested that progesterone has either a permissive or a facilitating effect on their evolution, or possibly both Magdalenat et al.
The treatment should be restricted to unresectable meningiomas. The spontaneous variety of evolution of these tumors makes a definitive evaluation of the beneficial effects very difficult, even though definite, sometimes spectacular improvement has been observed in about one-third of available reports. Instead of RU , an antiprogesterone without antiglucocorticosteroid activity would be welcomed.
Conversely, there are gliomas whose growth is sensitive to glucocorticosteroid that may benefit from antiglucocorticosteroid compounds Langeveld et al. While demonstrating antiglucocorticosteroid activity in vitro Philibert et al. This overcomes the hypocorticosteroid effect, which explains the good tolerance of RU when it is administered briefly, as in abortion or emergency contraception.
There are several potential uses of RU or antiglucocorticosteroid analogues. The long-term use of RU —for instance, to treat tumors—may be improved if a compound blocking steroid biosynthesis is given simultaneously. In breast cancer this could be an antiaromatase because production of estrogens increases when adrenal androgen hypersecretion occurs with RU treatment. An antiglucocorticosteroid with a short half-life should be useful for the kinetic studies of the hypothalamus-pituitary-adrenal axis, in particular to classify different types of depression Ammar et al.
In several instances, an acute increase of glucocorticosteroids, for instance, during the stress of aggressive conditions, might be antagonized by RU , which could therefore protect against immune depression. Conversely, RU might be detrimental in the pharmacological manipulation of septic shock Broukaert et al. It is not impossible that RU or another antiglucocorticosteroid deprived of antiprogesterone effect might be useful in the treatment of certain cases of psychosis or arterial hypertension, since these two pathological features are remarkably cured when present in Cushing's syndrome treated with RU administration [here RU has been a lifesaving drug see review in Chrousos et al.
However, this will concern only a small number of patients. Whether some chronic conditions involving hypercortisolism, such as certain forms of obesity, can benefit from RU is still debatable Okada et al. The use of RU or analogues has been suggested in premenstrual syndrome, postmenopausal flushes, Alzheimer's disease, and AIDS, but there is currently no firm scientific background to justify trials. More generally, any long-term treatment with an antiprogestin or an antiglucocorticosteroid should be carefully followed up. Chronic antiprogesterone activity may create an unopposed estrogenic state, counteract the osteogenic effect of P, or interfere with the activity of P in the central nervous system.
Signs of adrenal insufficiency may also develop. It is probably the local use of RU , or its derivatives with antiglucocorticosteroid activity, that will develop rapidly. Trials are on the way for treating glaucoma, and for accelerating or amplifying the slow healing of wounds and burns, particularly in stressed or aging patients who have increased or normal cortisol and low adrenal androgen levels.
Much work remains to be done Hodgen, I single out four approaches that I believe to be most important. The RU plus-misoprostol combined method is ready to be used at large. It works, is safe, and is close to being as convenient as a medical method of abortion may be.
Given the global demographic issue, the suffering of women, and related health problems, it must soon be made available in the United States—a key to further worldwide development. Studies must rapidly discern the best conditions for its distribution in parts of the world where there are obstacles, including developing countries. The early use of RU , as soon as a woman fears a pregnancy that she does not want, will help to defuse the abortion issue.
Research should be conducted to define convenient and safe contraceptive methods with RU or other antiprogestins. There are serious hopes, and it is now a matter of conducting systematic studies. However, it will take several years and a great deal of money. Significant success also will contribute to decreasing the practice of abortion as we know it.
Nonreproductive medicine should investigate the regulatory properties of RU and its derivatives in several diseases. The most cruel, breast cancer, should be first on the list of trials. Again, this may take time and money, but there already are clues that cannot be neglected. There is enough data to suggest that RU is only the first in a series of new compounds with significant differences that could be medically exploitable Table B1.
Therefore, basic, novel, interactive chemical and biological research should be continued forcefully. I would like to acknowledge the editorial work of Rod Fiddes, Ph. Potent and specific progesterone antagonists have been sought for many years. Although some progress had been made in developing such compounds Raynaud and Ojasoo, , it has been only a little more than a decade since the first progesterone antagonist, RU , was developed by researchers at Roussel-Uclaf Philibert et al.
Other progesterone antagonists have also been described Philibert et al. To date, all of the described progesterone antagonists also show at least some degree of glucocorticoid antagonism Raynaud and Ojasoo, ; Mao et al. Thus the search for the "ideal" progesterone antagonist continues. Although the mechanism of action of the various progesterone antagonists may differ, studies suggest that most, if not all of the antagonism, is mediated by the progesterone receptor.
The progesterone receptor is a member of a superfamily of nuclear receptors that includes the other steroid receptors as well as the thyroid hormone, retinoic acid, and vitamin D receptors Evans, In order to understand the mechanism of action of antagonists, it is first necessary to understand the structure and function of the receptors themselves.
The members of this family of receptors share three regions of homology. The locations of these three regions within the human progesterone receptor are shown in Figure B2. The first and most highly conserved is termed C1. It encodes the DNA binding domain and contains two zinc finger structures Evans, The other two regions of homology, C2 and C3, are small segments of the carboxyl terminus, which are contained within a larger region important for ligand binding and for receptor dimerization.
Upon activation, the receptors dimerize, bind to specific DNA sequences termed steroid response elements, and activate the transcription of target genes. Typically, the activation of receptors is studied by using artifical target genes on plasmids that contain one or more of the specific response elements placed 5' of a promoter and a cDNA for an enzyme such as chloramphenicol acetyl-transferase which can be easily assayed Denner et al.
The activity of the receptor can then be studied by transfecting the reporter gene and a plasmid that expresses receptor if necessary into a target cell, treating with the desired agonist or antagonist, and measuring the resulting enzyme activity. Although there are many similarities in the mechanisms of action of the various steroid receptors, there are also significant differences.
The structure and function of the human progesterone receptor are described below. Location of the conserved regions in the steroid-receptor superfamily. Shown here, as an example, is the structure of the human progesterone receptor. C1 is the conserved region containing the DNA binding domain. C2 and C3 are conserved regions important more Both are derived from the same gene, but are produced from different mRNAs Kastner et al.
These receptor forms share common hormone binding and DNA binding domains. Either form can activate transcription of a target gene in cells co-transfected with the corresponding expression vector for PR-A or PR-B, as well as a suitable reporter plasmid Bocquel et al. However, the two forms differ in their relative activities, depending upon the target gene studied Bocquel et al.
In the cases examined thus far, both forms are expressed in cells and in tissues that contain progesterone receptor Horwitz and Alexander, ; Lessey et al. Although it is presumed that both forms exist in the same cells, this has not been unequivocally demonstrated. The ligand binding domain resides in the carboxyl terminal 30 kDa of the progesterone receptor Figure B2.
Despite the large size of this domain, analysis of this region using both deletions and point mutations suggests that most of this region is required to maintain the high-affinity hormone binding activity Carson-Jurica et al. Photoaffinity labeling studies of the glucocorticoid receptor using R show that two amino acids, which are about amino acids apart in the linear sequence, are close enough in the three-dimensional structure of the receptor that they both react with the same portion of the R molecule Carlstedt-Duke et al.
This suggests that the region is extensively folded back upon itself to produce the binding pocket for the ligand. Consistent with these data is the observation that the entire hormone binding domain is relatively resistant to digestion by a number of proteases when bound with R Allan et al. Within this domain reside two additional functions of the receptor. The active form of the receptor is a dimer, and the region most important for receptor dimerization is found in the ligand binding domain Fawell et al.
In addition, this domain is important for transcriptional activation of steroid receptors. The DNA binding domain is a highly conserved region that is responsible for the DNA binding specificity of the receptor. The region contains two zinc finger structures Umesono and Evans, The first zinc finger is important for the interaction with DNA, and the second is involved in dimerization with the other receptor molecule Hard et al.
Although some members of the steroid-receptor family are capable of heterodimerizing with other members of the family Berrodin et al. However, there are two forms of the progesterone receptor, PR-A and PR-B, and these are capable of forming both homodimers and heterodimers as measured by gel retardation assays El-Ashry-Stowers et al. Whether such heterodimerization occurs in vivo and plays a role in preferential activation of specific target genes is not yet known. The amino terminal portion of the progesterone receptor is not required either for DNA binding or for hormone binding.
However, it is important for transcriptional activation Tasset et al. Studies have shown that there are two regions in the progesterone receptor that are important for transcriptional activation Bocquel et al. The first is the amino terminus of the protein, and the second resides in the hormone binding domain Bocquel et al. The relative importance of these two domains depends on both the target gene and the cell type in which they are examined.
In the absence of hormone, the progesterone receptor is found associated with several non-steroid binding proteins including two heat shock proteins, hsp90 and hsp70, as well as some less well characterized proteins Dougherty et al. The role or roles of these proteins in vivo have not been elucidated. These large receptor complexes each contain a single steroid binding molecule.
The receptors are not in the dimer form and do not bind to DNA, which suggests that one role of the non-steroid binding proteins is to inhibit DNA binding of the receptors in the absence of ligand. There is evidence, in the case of the glucocorticoid receptor, that the heat shock protein complex is important for maintaining the integrity of the hormone binding site in the absence of ligand Pratt et al. The steroid receptors, including the human progesterone receptor, are phosphoproteins Dougherty et al. The human progesterone receptor is phosphorylated at numerous sites Sheridan, et al.
Beck et al. Takimoto and coworkers have shown that the final phosphorylation that alters receptor mobility occurs only if the receptor can bind to DNA. Weigel and coworkers have shown that the chicken progesterone receptor is phosphorylated during in vitro transcription assays by a DNA-dependent kinase in HeLa nuclear extracts.
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This enzyme was identified as the double-stranded DNA-dependent kinase purified by Carter et al. Subsequent studies by Bagchi and coworkers have shown that the human progesterone receptor undergoes a similar DNA-dependent phosphorylation in vitro, suggesting that this enzyme may be responsible for the DNA-dependent phosphorylation observed in T47D breast cancer cells. The role of phosphorylation in progesterone-receptor function has not been determined directly.
However, receptor isolated from cells treated briefly with R so that the phosphorylation is enhanced shows enhanced specific DNA binding Beck et al. Moreover, treatment of cells with activators of kinases enhances the receptor-dependent transcriptional activity Beck et al. In the absence of hormone, the progesterone receptors is found in a complex with heat shock proteins in the cytosol fraction of cell homogenates. Based on these types of assays, the unliganded receptor was originally believed to be cytoplasmic. However, immunocytochemical studies suggest that in vivo the unliganded receptor is found in the nucleus Perrot-Applanat et al.
This binding is less tight than in the presence of hormone since receptor isolated from hormone-treated cells is tightly bound to the nuclear fraction and requires high-salt treatment for extraction. There is evidence that the progesterone receptor cycles continuously between the cytoplasm and the nucleus in the absence of hormone and that this recycling and nuclear retention require energy Perrot-Applanat et al. Taken together, the data suggest that in the absence of hormone, the bulk of the receptor molecules are loosely bound in the nucleus but that they cycle through the cytoplasm with perhaps a relatively short residence time in the cytoplasm.
In contrast, the distribution of the glucocorticoid receptor, which also cycles DeFranco, , appears to favor cytoplasmic localization in the absence of hormone. A proposed model for the mechanism of progesterone-receptor activation and the possible steps at which antagonists might act to inhibit receptor function are shown in Figure B2. Treatment with hormone results in dissociation of the receptor-heat shock protein complex, dimerization of the receptor, and binding to specific DNA response elements termed PREs, or progesterone response elements.
Although one or two of these elements placed in the 5' flanking region of a target gene are sufficient to produce a gene whose transcription is activated in response to progesterone Tsai et al. In some cases, genes that are steroid inducible do not appear to contain consensus steroid response elements in their 5' flanking regions.
Thus, the receptors may also act at nonconsensus sequences through interaction with other factors to induce or repress genes. A model for the mechanism of action of the human progesterone receptor. In the absence of steroid, the receptor is associated with heat shock proteins and is basally phosphorylated. In this model, each P represents a class of phosphorylation sites rather more Strategic Management Journal 19 3 Eisenberg, T. Journal of Financial Economics Fama, E. Farrell, M. Feujo, J. Godard, L.
Guesnier, B. Guido, F. Hartarska, V. Hermalin, B. Jensen, M. Kang, E. Khan, A. Klapper, L. Lascelles, D. Ledgerwood, J. Lipton, M. McGuire, P. Pablo A. Peter, K. Young, J. Rajan, R. Reberioux, A. Ricordel, P. Rock, R. Sallez, A. Sharma, M. Shleifer, A. Shephard, R. Udry, C. Yermack, D. Or, les objectifs social et financier sont parfois contradictoires.
Navajas et al. Tableau 9. Le terrain de la recherche portera donc sur les IMF. Or, les objectifs des IMF sont financiers et social. A cet effet, les IMF doivent:. On peut par ailleurs observer, comme le montre le Tableau 9. Dans la Figure 9. Figure 9. Il est donc difficile de savoir pourquoi les IMF finance tel projet au lieu de tel autre.
Le Tableau 9. Il constitue donc une charge pour une IMF. Brempong, K. Callan, S. Caves, D. De Bruyne, B. Bastiaensen , How to put social performance management into practice? Trias, Brussels. Fare, R. Grosskopf, M. Greene, W. Hermes, M. Kipesha, E. Kirjavainen, T. Kobou, G. Kohers, T. Labie, M. Lapenu, C. Luoma, K. Jarvio, I. Navajas, S. Scheiner, L. Meyer, C. Rochiquez — Meza J. Otero, M. Schepers, D. Journal of Business Ethics Stiglitz, E. Tulchin, D.
Woller, G. Qui offre des produits de microassurance? Cet input constitue le plus important. En observant le bas du Tableau Tableau Albert-Angers, F. Aliber, M. Amara, N. Ambapour, S. Banker, R. Bekolo Ebe, B. Bertelet, N. Bouman, F. Churchill, C. Liber, M. Coelli, T. Cohen, M. Conning, J.
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Debaig, G. De Bock, O. ILO: Geneva. Debreu, G. Emrouznejad, A. Germidis, D. Gregoriou, G. Henry, A. Herroro, I. Hulme, D. Mosley , Finance against Poverty , Routledge, Londres. Johnson, B. Sheely eds Kamdem Bukam, E. Malmquist, S. McCord, M. Steinmann, C. Tatin-Jaleran, M. Ingram and M. Working Paper. Modigliani, F. Pichette, C. Rietsch, C. Townsend, R. Vogel, C. Adams,, H. Graham and J. Figure Cette tendance est plus forte chez les entrepreneurs femmes comparativement aux entrepreneurs hommes. Aggarwal, S. Berger, A. Elsevier Science B.
Bourguignon, F. Turnovsky eds , Inequality and Growth. Theory and Policy Implications. Boungou Bazika, J-C, B. Makosso, J. Brown, M. Deininger, K. Diata, H. Dollar, D. Jakiela, D. Karlan, D. Khandker, Shahidur R. Makosso, B. Meza, D. Webb Montgomery, H. Mosley, P. Pitamber, S. Ravallion, M. Robinson, M. Sahn, D. Shaw, J. Simanowitz, A. Van Tassel, E. This paper explores correlates of credit access, effects of credit on economic wellbeing, and potential disparity in responses by sources of wellbeing, location and gender, while controlling for other correlates.
We used the Cameroun household consumption survey and a range of survey-based econometric methods that purge parameter estimates of potential intra-cluster correlation, endogeneity and sample selection bias. Access to credit is strongly associated with household economic wellbeing irrespective of source of wellbeing. Credit correlates significantly with economic wellbeing in rural areas, but not in urban areas; whereas education associates strongly with economic wellbeing in urban areas, but not in rural areas.
The implication is that rural wellbeing is more contingent on credit access than being educated, while urban wellbeing derives more from being educated than having credit access. Both credit access and education are significantly associated with wellbeing in male headed households, whereas only education correlates significantly with household wellbeing in female headed households.
The implication is that while male headed households rely on both credit access and education to boost wellbeing, their female counterparts appear to relie more on being educated than having credit access. The impact of credit can be enhanced by accompanying measures such as availability of sufficient funds, quality services by lenders, physical infrastructure, healthcare and training. Many studies show that by providing low-income households with access to financial services, the service providers help to improve their productivity and management skills, create jobs, smooth income and consumption flows, enlarge and diversify their businesses, and increase their income and other benefits, such as healthcare and education Morduch, ; Gulli, ; Khandker, ; Pitt and Khandker, ; Zeller, ; ADB, ; Parker and Nagarajan, ; Robinson, ; Khandker, ; Khandker and Faruque, ; Coleman, ; Morduch and Haley, ; Khandker, Participants in microfinance institutions are, therefore, expected to accumulate more assets and to enjoy increased household incomes, better nutrition and health, the opportunity to achieve higher levels of training, a decrease in vulnerability to economic shocks, greater empowerment, and in some cases, the opportunity to completely lift themselves and families out of poverty.
In this regard, microfinance has been the focus of development and poverty reduction activities for some time now Khandker, , yet because of the conflicting evidence from empirical studies policy analysts and political entrepreneurs still know relatively little about the extent of poverty reduction possible through microfinance institutions. Paramount among the limitations of the existing studies is the absence of a coherent econometric methodology that would make empirical findings more robust and valid for policy purposes.
Differences in research methodology and data quality seem to account for differences in research findings. In particular, endogeneity, sample selection and intra-cluster correlation concerns are generally not accounted for in econometric studies that attempt to assess the impact of credit on the poverty status of households. This lack of empirical rigour reduces the relevance of findings for policy purposes. Empirical studies to guide on the actual impact of micro-credit using Cameroonian data are simply unavailable.
In particular, this paper seeks to address the following questions: 1 what impact does microfinance have on household economic wellbeing? The main objective of this study is to evaluate the extent to which microfinance contributes in the process of poverty alleviation in Cameroun. The specific objectives are: 1 to evaluate the impact of microfinance on household economic wellbeing in Cameroun; 2 to determine factors influencing household access to microfinance loans; and 3 to disaggregate these effects by sources of wellbeing, residence and gender.
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The claim in this paper is that access to micro-credit and education engenders household economic wellbeing. Microfinance in Cameroun in its traditional form dates for over one century. Other MFIs are informal or projects. Cameroun has been described as a country of striking diversity, unfulfilled promise and tantalizing potential, with regions that abound in variety — geography, climate, people, education and economic structure World Bank, In spite of all these endowments, Cameroun has been steep in poverty for more than the past two decades.
The economic collapse led to the country not being able to pay its foreign debts, and to the poverty level mounting dramatically. The banking sector was particularly hit by the crisis. In the late s this sector collapsed with the rest of the economy. The restructuring of this sector led to the liquidation of many banks, the closure of almost all bank branches in the rural areas and small towns, and the retrenchment of many bank workers. This led to a great reduction in the financial coverage or penetration that was already quite limited.
The microfinance sector was bound to grow because financial intermediation is shallow all over the country, with a ratio of money supply to GDP at This reflects a very low rate of bank penetration. Nevertheless, the microfinance sector has grown rapidly in the past two decades.
Savings mobilized stood at CFA In the same year, more than CFA Recently, Fotabong noted that the microfinance market will grow even further during the next decade. Some former bank workers created savings and loan cooperatives, which have been functioning as semi-banks. This sector has however, expanded without an appropriate regulatory framework for many years. This shortcoming resulted in a lack of protection for depositors and in operations that fail to meet prudential standards. This led the government to establish operating modalities for savings and loan cooperatives.
In particular, the government has taken measures to protect depositors. Providing access to finance to the poor has been considered a tool for economic development and poverty reduction ADB, ; Morduch and Haley, ; Khandker, Market imperfections such as asymmetric information and transaction costs and the lack of collateral explain, at least in part, why the poor lack access to finance Meyer and Nagarajan, ; Stiglitz and Weiss, ; Binswanger and McIntire, However, innovative lending technologies such as joint-liability lending Ghatak, , , prior savings lending and co-making lending may serve as the solutions to asymmetric information problems and the lack of collateral.
The problem of asymmetric information in the financial markets for the poor and low income households is considered more serious because of the extremely high cost of screening and monitoring resulting in adverse selection Yaron et al. In addition, most of the poor lack education or are poorly educated and cannot provide standard collateral as required by the financial institutions Binswanger and McIntire, As a result, they are excluded from the financial sector and in most cases do rely only on the informal sector, which lends at extremely high rates of interest Meyer and Nagarajan, , Given the absence of financial markets for the poor, policymakers are confronted with the debate to subsidize or not to subsidize financial institutions in providing financial services to the poor Rhyne, ; Robinson, ; Gonzalez, This debate has been articulated mainly between the two major strands in the conceptualisation of microfinance: the poverty reduction approach and the financial systems approach.
The poverty reduction approach aims at providing cheap financial services to the poor, especially the very poor, through governmental subsidies with the main expectation that financial services would contribute to poverty reduction. The financial systems approach on the other hand aims at applying commercial finance principles and building a financial intermediation system for the poor without subsidisation. Irrespective of the approach to microfinance, millions of poor and low-income households need financial services for various reasons: their demand for livelihood activities such as food, healthcare and education; and for small business opportunities, which generate jobs and income.
However, lack of quality work for the poor appears to be one among the major concerns. If the poor and low income households have opportunities to access credit, it is believed that they may increase their living standard from returns on their investments. It is well documented that the primary concern is to deal with excessive demand for credit and the view that credit is essential for economic activity, for both poor households and micro-enterprises ADB, Generally, the commercial banks are reluctant to lend to the poor because of the high costs of processing the small loan amounts poor people usually demand and also because of market imperfections.
As a result, the low-income households with business prospects have to resort: i to borrow from informal sources especially from moneylenders, who charge very high interest rates; or ii to give up their business plans because of lack of money. Besides credit, there is also the demand for savings and financial assets and other services such as insurance. The low-income households need safe and convenient savings services. Contrary to some preconceptions, there is some evidence that the poor have the capacity and willingness to save Rutherford, ; CGAP, They need to save for emergencies, future investment, consumption, social obligations, the education of their children, and many other purposes ADB, The demand for financial services by the poor and low income households can be seen from the gap between the number of low income households and the number of households having access to financial services Gibbons and Meehan, ; Navajas et al.
Gibbons and Meehan show that of about The situation in Africa and especially Cameroun is worse. The low rates of coverage suggest that much needs to be done to improve household access to financial services. Some literature shows that access to credit has ambiguous impact on poverty reduction Gonzalez, However, many recent empirical studies show that access to credit has a positive impact on household economic welfare Khandker, ; Panjaitan et al. The literature also shows that most microfinance programs do not serve the poorest, but when they do, the poorest can benefit through increased income and reduced vulnerability Morduch and Haley, There is also some evidence that the degree of poverty may affect the response.
Better-off poor households have a larger positive response than the very poor Remenyi and Benjamin, ; Coleman, A study by Hao using Vietnamese data found that household credit contributes positively and significantly to the economic welfare of households in terms of per capita expenditure, per capita food expenditure and per capita non-food expenditure.
The study also found that credit has a greater positive effect on the economic welfare of poorer households and that the age of the household head, the household size, land ownership; savings and the availability of credit at village level are key factors that affect household borrowing. Many researchers have postulated that the provision of financial services to the poor through microfinance is a powerful means of providing low income households with the chance to escape from poverty and to transform their lives.
It is also evident that there is a strong demand for small-scale commercial financial services — both credit and savings — from low income households Robinson, The strong demand for financial services by low income households, together with the evidence that access to credit reduces household poverty, provides clear incentives for policymakers to promote a framework for providing financial services to low-income households. To access how much household borrowing contributes to household economic wellbeing and poverty and determinants of household borrowing in Cameroun, we consider a framework in which two sets of actors — households and lenders, interact in the credit market.
However, credit access or the amount of credit supplied to a household that a researcher can observe, is the result of the interaction between demand and supply. The difficulty is that the factors which are likely to affect household demand for credit, are also likely to affect supply of credit. For example, ownership of farmland may positively affect household demand for credit, while it may also positively affect the supply of credit if lenders consider it as collateral in the credit market.
This implies that credit supply and demand curves cannot be easily identified. Thus, we consider household borrowing, rather than separately considering demand and supply. In order to assess the impact of credit on household economic wellbeing, we employ a production function in which credit is introduced as a separate explanatory variable.
Household wellbeing is typically reflected in indicators of income and expenditure. At the household level, the economic wellbeing is also likely to be affected by household characteristics such as the age of household head, the education of household head, total farming area, etc. At community and regional levels, household wellbeing is possibly affected by community and regional characteristics.
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For example, the prices of selected goods and services in the community and region and cluster specific characteristics may affect household expenditure or income. These characteristics may be recognised as local market characteristics. Household economic wellbeing is also affected by household and local market characteristics that we cannot observe or measure. For instance, households exerting more effort may generate higher income.
Control variables may therefore include household characteristics, local market characteristics and unobservable characteristics. In this analysis, it is likely that both credit access and education literacy status of household head may be endogenous in the wellbeing generating function, thus the need to present them as separate from the vector of potential exogenous variables. The household income generating function may take the structural form:. Notice that we consider neither the demand nor the supply of household credit, but the function of household borrowing or access to credit for a representative household.
The understanding and interpretation of determinants of household borrowing should therefore reflect both the demand and the supply side. Since borrowing is contingent on making loan applications and educational status is a decision variable, then it is possible that these variables are jointly determined with the economic well being generating function. Even if the problem of endogeneity of credit access is resolved, our next concern is about the selection of the estimation sample.
In theory, the demand and supply of credit would determine the price and amount of credit granted to a representative household Hao,
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