Human chorionic gonadotropin (hCG) modulation of TIMP1 secretion by human endometrial stromal cells facilitates extravillous trophoblast invasion in vitro.

STUDY QUESTION: Are secreted extracellular matrix (ECM) remodelling elements, relevant to embryo implantation and placentation, modified by hCG in endometrial stromal cells (ESCs)? SUMMARY ANSWER: hCG decreases tissue inhibitor of metalloproteinase 1 (TIMP-1) secretion in ESCs, thereby facilitating extravillous trophoblast invasion in vitro. WHAT IS KNOWN ALREADY: Successful embryo implantation and placentation depend on the appropriate invasion of the trophoblast into the maternal endometrial stroma. hCG is one of the earliest embryo-derived secreted signals in the endometrium which abundantly expresses hCG receptors. However, there is little data concerning the effects of hCG on endometrial ECM remodelling with respect to embryo implantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study was conducted in an academic research laboratory within a tertiary-care hospital. Samples were collected from 36 women undergoing benign gynaecological surgery during the mid-secretory phase. ESCs were isolated and stimulated with hCG (10 UI/ml) or vehicle. Conditioned media (CM) were analysed to determine changes in the secreted profile of nine matrix metalloproteinases (MMPs) and three tissue-specific inhibitors of MMPs (TIMPs) using an ELISA array. Data were confirmed by gelatine zymography, western blot and ELISA. The HTR8/SVneo cell line served as a model for trophoblast cells. The invasive potential of trophoblast cells was assessed using Transwell invasion assays under CM or co-culture conditions with ECS and the role of regulated molecules was examined by using immunoprecipitation in CM prior to the assessment of invasive potential. MAIN RESULTS AND THE ROLE OF CHANCE: MMP-2 levels increased 30%, whereas TIMP-1 levels decreased 20% in CM from ESCs stimulated with hCG (P < 0.05). Gelatine zymography confirmed an increase in MMP-2 activity (P < 0.05). ELISA and western blotting also confirmed the reduction in TIMP-1 upon hCG treatment (P < 0.05). Invasion assays revealed a ∼50% increase in invading HTR8/SVneo cells in chambers with hCG-stimulated ESCs compared with the control (P < 0.05). Immunodepletion of TIMP-1 from control ESC-CM partially resembled the effect of CM from hCG-stimulated ESCs in the trophoblast invasion assays. LIMITATIONS, REASONS FOR CAUTION: The assays were performed in vitro and ESCs were not decidualized, therefore they reflected the very early stages of embryo implantation or the advanced stages when decidualization fails. WIDER IMPLICATIONS OF THE FINDINGS: Our data suggest that hCG induces endometrial stromal extracellular remodelling by modulating secreted MMP-2 and TIMP-1. This regulation may be physiologically relevant because it increases the invasive potential of trophoblast-derived cells. At present, few data exist concerning the implications of hCG and endometrial ECM remodelling in embryo implantation. Hence, our results should be confirmed by further in vivo studies. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by FONDECYT 11100443, PBCT-PSD51 (IDIMI) and FONDAP 15010006. None of the authors have any conflicts of interest to declare.

Resumption of ovarian function during lactational amenorrhoea in breastfeeding women with polycystic ovarian syndrome: endocrine aspects.

BACKGROUND: The aim of this study was to evaluate the changes in gonadotrophin concentrations and the dynamics of the episodic fluctuations of circulating LH during night-time, in fully breastfeeding normal women and in those with polycystic ovarian syndrome (PCOS) during lactational amenorrhoea and after weaning, in order to provide insights into the onset of this syndrome. Additionally, ovarian activity was evaluated by ultrasound examination and steroid concentrations. METHODS: Twelve lactating PCOS (LPCOS) women and six normal lactating (NL) women of similar age were selected. On the 4th and 8th week postpartum (PP) and eight weeks after weaning, blood samples were collected every 10 min (10.00--20.00h). Gonadotrophin concentrations were determined in all samples. Steroid hormones were measured in one fasting sample and ovarian morphology was assessed by ultrasound. RESULTS: On the 8th week PP, LH pulse frequency was higher and FSH concentrations were lower in LPCOS women compared with NL women, and steroid hormone concentrations remained low, except for androstenedione which was higher in LPCOS patients. After weaning, similar differences were observed between both groups. PCOS patients also showed enlarged ovaries with a PCOS pattern in the three study periods. CONCLUSIONS: The enlarged ovaries associated with higher androstenedione concentrations suggest that PCOS is a primary ovarian defect, making it difficult to establish if the abnormal LH pattern observed in these women is primary or secondary to the ovarian dysfunction.

Leptin and reproduction.

Leptin, the product of the ob gene, is a small peptide molecule synthesized by white adipocytes with an important role in the regulation of body fat and food intake. Leptin and leptin receptor mRNA were first detected in the brain and hypothalamus but now their ubiquitous presence has been demonstrated. Leptin receptor signal transduction involves the activation of signal transducer and activator of transcription (STAT)-3, a member of the transcription family of proteins. Leptin is regulated by hormones and cytokines, interleukin-1, tumour necrosis factor-alpha and transforming growth factor-beta, linking this molecule with the inflammatory response. In addition, emerging evidence has demonstrated that this molecule is related to reproductive function. This small protein is present in the ovary and decidua, in mature oocytes and during embryonic development and trophoblast invasion. Animal models have demonstrated that leptin-deficient ob/ob mice are sterile; however, fertility can be restored by exogenous leptin. In addition, embryos implanted in STAT-3-deficient mice degenerate rapidly and are the target disruption of STAT-3-provoked embryonic lethality. Leptin acts as a novel placental hormone participating in the control of fetal growth and development. Leptin could be a modulator for invasive features of cytotrophoblast cells. We postulate that leptin may have an autocrine/paracrine role in human implantation and placentation.

Leptin and leptin receptor are expressed in the human endometrium and endometrial leptin secretion is regulated by the human blastocyst.

Embryonic implantation is a crucial event for the human reproductive function. Cytokines and paracrine molecules have been proposed as putative local regulators of this process. The leptin or the OB protein has been linked to the reproductive function and inflammatory response. In the present study, we describe for the first time the expression of leptin and leptin receptor (long form) in the secretory endometrium and that endometrial leptin secretion is regulated in vitro by the human blastocyst. Leptin and leptin receptor messenger RNA and protein were identified in secretory endometrium and in cultured endometrial epithelial cells (EECs) by RT-PCR, Western blot, and immunohistochemistry. The concentrations of immunoreactive leptin secreted by human embryos alone or cocultured with EECs were also assessed. We found that human blastocysts secrete significantly higher levels of leptin than arrested embryos. In contrast, leptin concentrations secreted by arrested embryos cocultured with EECs were significantly higher than blastocysts cocultured with EECs. These findings suggest that the human endometrium is a site for local production and a target tissue for circulating leptin. Expression of leptin and its functional receptor in the endometrium and regulation of endometrial leptin secretion by the human embryo suggests that the leptin system may be implicated in the human implantation process.

A quantitative evaluation of alpha1, alpha4, alphaV and beta3 endometrial integrins of fertile and unexplained infertile women during the menstrual cycle. A flow cytometric appraisal.

The expression of integrin molecules alpha1beta1, alpha4beta1 and alphaVbeta3 within endometrial tissue has been proposed as a marker of uterine receptivity during the implantation window. The present investigation examines by flow cytometric analysis the concentrations of alpha1, alpha4, alphaV and beta3 integrin subunits in endometrial stromal (ESC) and epithelial cells (EEC) in two groups of women throughout the menstrual cycle: normal fertile women (n = 27) and women with unexplained infertility (n = 26). Integrin concentrations in endometrial cells were calculated in relative fluorescence units against a negative cellular control. The assessment of integrin subunits detected the protein in ESC and EEC from the late proliferative to the late secretory phase. In both groups of women, the alpha1 was the highest integrin expressed in ESC and EEC throughout the menstrual cycle. All women exhibited low concentrations of alpha4-EEC at the time of the implantation window. Infertile women expressed lower concentrations of the alpha4-ESC during the proliferative and early secretory phase while lower concentrations of the alpha1-ESC were seen during the late secretory phase. Interestingly, the infertile women expressed lower concentrations of beta3-EEC in the early, mid-secretory and late secretory phases (P < 0.05). Infertile women also expressed lower concentrations of alpha1-EEC and alphaV-EEC during the late secretory phase (P < 0.05). It can be concluded that the quantitative determination of beta3-EEC by flow cytometry confirmed its potential feature as a marker of endometrial receptivity at the time of the implantation window. In addition, the defective expression of the alpha1-ESC found in the late secretory phase might be associated with the poor fertility outcome of women with unexplained infertility.

Regulation of human luteal steroidogenesis in vitro by nitric oxide.

To evaluate the effect of nitric oxide (NO.) in human corpus luteum (CL) function, we investigated the expression and the presence of NO. synthase (NOS) in the human CL and the action of NO. on the in vitro luteal steroid production. The expression of endothelial NOS (eNOS) in early, mid-, and late CL was assessed by reverse transcriptase polymerase chain reaction (RT-PCR) and the immunohistochemical study was performed in human CL histological sections by using monoclonal antibodies (MAbs) against the distinct NOS isoforms. In addition, seven human mid-CLs were enzymatically dispersed, and the cells were cultured with NO. donor compounds. Steroid production was measured in the culture media by specific radioimmunoassay. The results show that the expression of eNOS was highly detected in mid- and early CL, and to a lesser extent, in late CL. Meanwhile, the immunohistochemical study indicated that both isoenzymes of NOS were expressed in mid-human CL, eNOS being the more abundant isoform present. On the other hand, functional studies showed that NO. donors (L-arginine [L-Arg] and sodium nitroprusside) elicited an inhibitory action on steroid synthesis, preferentially on estradiol production by the luteal cell cultures (p < 0.05). In conclusion, the NO-NOS system is present in the human CL, and it may serve as a modulator of the in vitro human luteal steroidogenesis.

Regulatory role of angiotensin II on progesterone production by cultured human granulosa cells. Expression of angiotensin II type-2 receptor.

The role of angiotensin II (AngII) in ovarian steroidogenesis is not clearly understood. In order to study its action on progesterone synthesis and to determine which receptor subtype is involve, granulosa cells obtained from women undergoing in-vitro fertilization were cultured for 2 or 4 days and then incubated in the presence of AngII (10(-7) M) with or without human chorionic gonadotrophin (HCG, 10 IU/ml) for 3 or 18 h. In cells cultured for 2 days, incubation with AngII decreased progesterone secretion by 36%, and inhibited activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) by 87% (P < 0.05), although its expression was not significantly reduced. However, in cells cultured for 4 days, progesterone production was enhanced by incubation with AngII (38%), and no change was observed in 3 beta-HSD expression. Both inhibitory and stimulatory effects were dose-dependent. Progesterone secretion was increased (93%) by incubation with HCG of cells cultured for 4, but not for 2 days, and no potentiation was observed with AngII. Treatment with PD123177 completely blocked the action of AngII and decreased the HCG-stimulated secretion of progesterone by 27%. Angiotensin type-2 (AT2) receptor mRNA was expressed in cells cultured for 4 days. In conclusion, AngII showed a regulatory role in in-vitro progesterone production by human granulosa luteinized cells, modulating the activity of 3 beta-HSD. It is likely that these actions may be mediated via membrane receptors, possibly of the AT2 receptor family.

Neuroendocrine mechanism of anovulation in users of contraceptive subdermal implant of nomegestrol acetate (Uniplant).

OBJECTIVE: To evaluate a nomegestrol acetate subdermal contraceptive implant's (Uniplant; Thermex, Monaco) effect on the hypothalamus-pituitary-ovarian axis. DESIGN: A prospective clinical trial. SETTING: San Borja-Arriarán Clinical Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling healthy women. INTERVENTION(S): Insertion of Uniplant. MAIN OUTCOME MEASURE(S): Luteinizing hormone pulse and endocrine profiles were assessed before, 48 hours after insertion, and after prolonged use of the implant. RESULT(S): Anovulation was noted in 100% of users in the first month. Seventy percent of subjects demonstrated follicular development with the absence of ovulation and an endocrine profile similar to the follicular phase: (LH pulse/8 hours 6.85 +/- 0.67, LH amplitude 3.54 +/- 0.65 mIU/mL (conversion factor to SI unit, 1.00), and E2 193 +/- 29.4 pg/mL (conversion factor to SI unit, 3.67), whereas 30% demonstrated no follicular activity with an endocrine profile similar to the luteal phase: (LH pulse/8 hours; 3.66 +/- 0.66, LH amplitude 5.76 +/- 1.73 mIU/mL, and E2 67.5 +/- 4 pg/mL. Clinical characteristics, serum gonadotropin concentration, and LH pulse characteristics failed to predict which subjects would initiate or remain devoid of follicular activity. CONCLUSION(S): Uniplant results in anovulation via two mechanisms: hypothalamic suppression in subjects who lack follicular development, and likely suppression of the pituitary LH surge in subjects who initiate follicular activity.

PIP: Findings are reported from a study of a nomegestrol acetate subdermal contraceptive implant's (Uniplant) effect upon the hypothalamus-pituitary-ovarian axis. 10 normally cycling healthy women aged 22-36 years requesting a contraceptive method at San Borja-Arriaran Hospital's family planning clinic participated in the prospective clinical trial. Luteinizing hormone pulse and endocrine profiles were assessed before insertion, 48 hours after insertion, and after prolonged use of the implant. Anovulation was noted in 100% of users in the first month. 70% of subjects demonstrated follicular development with the absence of ovulation and an endocrine profile similar to the follicular phase, while the remaining 30% demonstrated no follicular activity with endocrine profile similar to the luteal phase. Clinical characteristics, serum gonadotropin concentration, and LH pulse characteristics failed to predict which subjects would initiate or remain devoid of follicular activity. Uniplant therefore results in anovulation through hypothalamic suppression in subjects who lack follicular development and the likely suppression of the pituitary LH surge in subjects who initiate follicular activity.

Changes in the menstrual bleeding of users of a subdermal contraceptive implant of nomegestrol acetate (Uniplant) do not influence sexual frequency, sexual desire, or sexual enjoyment.

OBJECTIVE: To evaluate the effect of menstrual changes induced by a nomegestrol acetate subdermal contraceptive implant (Uniplant; Thermex, Bahia, Brazil) on users' sexuality. DESIGN: Prospective observational survey. SETTING: San Borja-Arriarán Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling healthy women and their partners. INTERVENTION(S): Structured interview before and during use of the contraceptive. MAIN OUTCOMES MEASURE(S): Sexual frequency, desire, and enjoyment; perception of health; and contraceptive satisfaction. RESULT(S): During the use of the implant more women reported irregular cycles (32% versus 11%) and vaginal spotting (38% versus 19%). Frequency of sexual relations was unchanged (2.3 versus 2.5/wk) but the percent of couples engaging in sexual relations during vaginal spotting increased (28% versus 11%). There was no significant difference in the percent of men or women who reported an increase, or decrease, in perceived sexual desire, sexual enjoyment, or perception of health during the use of Uniplant. CONCLUSION(S): Despite the alterations in menstrual cyclicity and the occurrence of spotting, the use of a contraceptive subdermal implant of nomegestrol acetate did not effect desire for, enjoyment of, or frequency of sexual relations in users.

PIP: Findings are presented from a study evaluating the effect of menstrual changes induced by a nomegestrol acetate subdermal contraceptive implant (Uniplant) on users' sexuality. The Uniplant implant evaluated is manufactured by Thermex of Bahia, Brazil. New subjects enrolled in a phase III clinical trial of the implant at San Borja-Arriaran Hospital, University of Chile, School of Medicine were observed prospectively. The participants were 118 normally cycling healthy women of median age 28 years and 60 male partners of median age 31 years. A structured interview was held before and during use of the contraceptive. Before insertion of the implant, 11% of the women reported irregular menstrual cycles, 19% reported vaginal spotting, and 11% of the couples reported engaging in sexual relations during vaginal spotting. During use of the implant, 32% of the women reported irregular cycles, 38% reported vaginal spotting, and 28% of the couples reported engaging in sexual relations during vaginal spotting. The frequency of sexual relations remained unchanged at 2.3-2.5 acts of coitus per weeks. There was no significant difference in the percentage of men or women who reported an increase or decrease in perceived sexual desire, sexual enjoyment, or perception of health during the use of Uniplant.

Autocrine/paracrine regulation of normal human corpus luteum development.

The human corpus luteum (CL) is a transient endocrine gland regulated primarily by the age-dependent action of LH/hCG, which initiates a series of cell-specific processes necessary for the structure and also function of the gland. An extensive local regulation of the luteal function also exists, based on the heterogeneity of the cellular composition of the CL. It is most likely that interactions occur among the different subpopulations of steroidogenic (large and small luteal cells) and nonsteroidogenic cells (leukocytes, endothelial cells, and fibroblasts). Therefore, local produced substances, including steroids, growth factors, reactive oxygen species, and, recently, nitric oxide, may modulate luteal life span. The knowledge of the basic events involved in the control of human luteal function may lead to a better understanding of the physiopathology of the human menstrual cycle.

Results of a user satisfaction study carried out in women using Uniplant contraceptive implant.

A study of the acceptability of Uniplant, a 12-month single implant of nomegestrol acetate, included 819 women from Africa, Latin America, and China, participating in a clinical trial of Uniplant. A standard, pre-coded questionnaire was specially designed for this purpose and applied at the moment of removal of implant, either at the end of 12 months of use or at the time of discontinuation for whatever reason. The level of satisfaction proved high when users' comparison with their previous contraceptive method, users' recommendation of Uniplant to others, users' intention to use the method in the future, and service satisfaction were taken into consideration. Uniplant was considered easy to use, safe (low risk of pregnancy), and also to cause fewer side effects than other methods. When asked about the least liked feature of Uniplant, almost half the respondents said that there was nothing that they disliked and about one-third mentioned the changes in their menstrual pattern. However, according to the clinical trial, over half of the Uniplant users have bleeding patterns similar to untreated cycles. The majority of respondents did not feel any discomfort during the procedure of insertion and removal of the implant. About 70% of patients in the study stated that they required contraception for more than one year and most of these women said that they did not mind having to change the implant every year.

Differential steroidogenic response of human luteal cell subpopulations.

The differential capacity for steroid synthesis of human luteal cell subpopulations was investigated in a well defined cell culture system. Corpora lutea were enzymatically dissociated, and the two cell types were obtained by a discontinuous Percoll gradient. Both cell types were cultured for 24 h with dibutyryl cAMP (1 mM), oestradiol (2.5 microM) and testosterone (1 microM). Steroid production was measured in the culture media and aromatase activity for both cell type subpopulations was also determined. Basal production of progesterone, oestradiol and testosterone was significantly greater in large cells than that in small cells (P < 0.05). Nevertheless, a greater response of small cells to several in-vitro treatments was observed. Thus, synthesis of progesterone, oestradiol and testosterone was significantly stimulated in these cells (P < 0.05) by dibutyryl cAMP. Interestingly, a 3.3-fold increase of progesterone production was also observed in the large luteal cell subpopulation. When oestradiol was added to the culture media, a 36% decrease of progesterone production (P < 0.05) by small cells was obtained, while progesterone synthesis by large cells was not significantly affected. Testosterone treatment of cells enhanced oestradiol production by both cell subtypes (P < 0.05), although the stimulatory action was greater in the small cell cultures (5.9-fold). These data indicate that the steroidogenic activity of the small cell subpopulation is highly dependent on endocrine and paracrine stimulatory mechanisms, while large cells possess a greater intrinsic steroidogenic capacity.

Localization of insulin-like growth factor (IGF-I) and IGF-I receptor expression in human corpora lutea: role on estradiol secretion.

OBJECTIVE: To determine whether insulin-like growth factor (IGF-I) and its receptors are expressed by human corpus luteum (CL) and to establish the effect of IGF-I on E2 biosynthesis in human luteal cell cultures. DESIGN: Middle corpora lutea were obtained from women undergoing surgical sterilization. The tissue was frozen for binding and in situ studies or dispersed for cell cultures. SETTING: Procedures were performed at the San Borja-Arriarán Hospital, National Health Service, and Institute of Maternal and Child Research, Faculty of Medicine, University of Chile. PATIENTS: Twelve patients aged 30 to 40 years requesting surgical sterilization in our institution. The laparotomy was scheduled 6 to 8 days after ovulation. MAIN OUTCOME MEASURES: Expression of IGF-I and IGF-I receptor messenger RNAs (mRNAs) by in situ hybridization. Concentration of IGF-I receptor and binding characteristics. Production of E2 by luteal cells. RESULTS: The binding of IGF-I was detected in middle human CL membranes. In addition, this tissue expressed the mRNAs of IGF-I and its receptor. In culture, IGF-I caused a progressive increase on E2 production. CONCLUSION: These data suggest that the IGF-I system is present in middle human CL. The topographic distribution of IGF-I and its receptors and the ability of IGF-I to stimulate E2 secretion strongly suggest that IGF-I has a role as a paracrine or autocrine regulator of the human luteal function.

Multicenter clinical trial on the efficacy and acceptability of a single contraceptive implant of nomegestrol acetate, Uniplant.

Uniplant, a single Silastic implant containing nomegestrol acetate, provides contraceptive efficacy for one year. Uniplant use for one year was studied in 1,803 healthy women of reproductive age, enrolled from 10 centers in 9 countries, after informed consent. Implants were placed subdermally either in the upper arm or in the gluteal region. Two-hundred-seventy-six subjects discontinued prior to completing one year of study. Cumulative discontinuation rate at 12 months was 15.72%. Medical reasons for discontinuation were principally menstrual-related. Fifteen pregnancies occurred during the one year study period, resulting in a 12-month net cumulative pregnancy rate of 0.94%. Approximately 56% of subjects using Uniplant had bleeding patterns similar to normal menstruation. Results from this study confirm that Uniplant is an efficient, well tolerated, 12-month contraceptive implant, with the advantage of easier insertion and removal of the single implant compared to other multiple implant methods.

Functional luteolysis in response to hydrogen peroxide in human luteal cells.

To evaluate the effect of reactive oxygen species in human corpus luteum function, we investigated whether hydrogen peroxide (H2O2) affects the in vitro luteal cell production of steroids. H2O2 treatment (1.0-100 microM) of mid and late luteal cell cultures elicited a dose-dependent decrease in basal progesterone production. However, treatment of mid luteal cells with a low concentration of H2O2 (0.01 microM) significantly stimulated progesterone secretion (P < 0.05). In addition, H2O2 (100 microM) markedly inhibited human chorionic gonadotropin (hCG)-stimulated progesterone and estradiol secretion. cAMP production was enhanced (2.4-fold, P < 0.05) by hCG treatment of luteal cells. The addition of H2O2 (0.1-100 microM) to hCG-stimulated luteal cell cultures elicited a decrease in cAMP concentration (P < 0.05) and in the specific binding of radiolabeled hCG by luteal cells. Progesterone and estradiol production stimulated by dibutyryl cAMP were significantly inhibited by H2O2 (P < 0.05). These findings suggest that H2O2 interferes with basal steroid production and, in hCG-stimulated conditions, it may inactivate the gonadotropin-receptor complex. The anti-steroidogenic action of H2O2 therefore raises the possibility of a modulatory role of H2O2 in human luteal steroidogenesis.

Attitudes and practice of couples regarding sexual relations during the menses and spotting.

To determine attitudes and practices regarding sexual relations during menstruation and vaginal spotting, a cross-sectional descriptive survey was performed at the Instituto de Investigaciones Materno Infantil, Universidad de Chile, Santiago, Chile. A total of 287 women and 206 men were randomly selected from an urban population. Attitudes, beliefs, and practices regarding sexual relations during vaginal bleeding were surveyed and stratified by educational level and other demographic characteristics. Overall, 70% of women and 72% of men were found to avoid sexual relations during menstruation. Fifty-four percent of women and 60% of men avoided sexual relations during vaginal spotting. Women with higher education (technical or university) were less likely to avoid sexual intercourse compared to those with a lower educational level (basic or secondary education) during menstruation (73% vs. 57%) and vaginal spotting (69% vs. 34%). Men with a higher educational level (university) avoided intercourse less frequently when their partner was spotting (48% vs. 64%). As many methods of contraception affect a woman's menstrual cycle, they therefore may affect the intimacy of a couple. Counseling and education regarding the menstrual cycle and expected alterations by a contraceptive method may reduce any negative impact of a contraceptive device on a couple's sexual life.

[Effect of chronic blockade of the opiodergic receptor on insulin resistance in a hyperandrogenic woman]. / Efecto del bloqueo crónico del receptor opioidergico sobre la insulino-resistencia en una mujer hiperandrogénica.

We report a woman with insulin resistance associated with hyperandrogenism and acanthosis nigricans (HAIR-AN syndrome) treated during 30 days with the prolonged action opioid antagonist Naltrexone. During its administration, decreases in basal blood glucose and serum insulin, insulin and glucose response to a glucose load and plasma testosterone were observed. These findings suggest that opioid activity could play a critical role in the physiopathology of hyperinsulinemia in hyperandrogenic women.

Morpho-functional study of human luteal cell subpopulations.

It has been reported that the mammalian corpus luteum is composed mainly of two subpopulations of luteal cells (large and small) of different morphology and function. The aims of this study were first to characterize cytologically the human corpus luteum throughout the luteal phase, and second to establish the in-vitro steroidogenic capacity of a well-defined human mid-luteal cell system. The results show that the most predominant (> 70%) cell shape, is polyhedric, and the number of cells per unit area is significantly different in the early, mid- and late corpus luteum (P < 0.005). Moreover, small cells (< 22 microns) were most common (56.8%) in all tissues analysed. On the other hand, both subpopulations synthesized progesterone, oestradiol and testosterone, although a significantly greater production of basal steroids was observed in large luteal cells (P < 0.05). Nevertheless, the response of small cells to human chorionic gonadotrophin (HCG) was significantly greater (P < 0.05) than that of large cells, in agreement with the preferential specific binding obtained for [125I]HCG to the small cell subpopulation. In summary, these results indicate that the human corpus luteum possesses distinct cell types, which may be related to endocrine function and its control.

Infertility after 8 years of marriage: a pilot study.

With the objective of measuring the prevalence and duration of infertility in a developing country, a retrospective cross-sectional study was designed. The survey was conducted at the Department of Obstetrics and Gynaecology, Hospital Sn. Borja-Arriaran, Mother and Child Research Institute, University of Chile, Santiago, March-September 1990. The study population comprised 474 women 15-45 years old selected at random from the 11,289 weddings that took place in downtown Santiago, Chile, in 1982. The reproductive history for the preceding 8 years was obtained through home interviews with the women conducted by midwives. The main outcome measures were the prevalence and duration of infertility. The results in this sample showed a 7.04% (95% confidence interval 6.21-7.87) prevalence of infertility after 8 years of marriage with a mean duration of 23 months. It is concluded that after 8 years of marriage about one out of 25 women is infertile (4.01%). This identified a group of patients that would benefit from a programme of assisted reproductive technology.