Biomedical subjects

L Devoto

Publications and source records attributed to L Devoto.

At least 37 records · Page 2Linked to original sources

PubMed1998

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.

Adult↗

PubMed1997

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.

Adolescent↗

PubMed1997

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.

Adult↗

PubMed1997

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.

Corpus Luteum↗

PubMed1997

Hormonal profile, endometrial histology and ovarian ultrasound assessment during 1 year of nomegestrol acetate implant (Uniplant).

The present study assesses the endocrinological, endometrial histology and vaginal ultrasound profiles of nomegestrol acetate subdermal implant users at varying times after insertion. Follicle stimulatory hormone, luteinizing hormone, oestradiol, progesterone, vaginal ultrasound assessment of the ovaries and the histological dating of the endometrium were serially assessed for a period of 50 days immediately after the insertion, and after at 6 months and 12 months of use. The endocrinological results of this prospective observational clinical trial indicated that 75% of the cycles across the study period in Uniplant users were anovulatory, 63% showing development of a persistent non-luteinized follicle. Anovulatory cycles devoid of follicular development were seen primarily in the first months after Uniplant insertion. Ovulatory cycles represented 25% of the Uniplant cycles. Inadequate luteal phase or disregulation of follicular growth was a common feature of ovulatory cycles. In conclusion, these findings suggest that the contraceptive mechanisms of a single nomegestrol acetate subdermal implant involve prevention of follicular growth, development of a persistent non-luteinized follicle, inadequate luteal phase and disruption of the endometrial architecture.

Adult↗

PubMed1997

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.

Angiotensin II↗

PubMed1996

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.

Adult↗

PubMed1996

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.

Adult↗

PubMed1996

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.

Adult↗

PubMed1996

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.

Adult↗

PubMed1995

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.

Adult↗

PubMed1995

Multihormonal regulation of progesterone synthesis in cultured human midluteal cells.

The objectives of this investigation were to examine in vivo insulin like-growth factor-I (IGF-I) secretion by the human midcorpora lutea (mid-CL) and the effects of IGF-I, hCG, FSH, and human GH on progesterone (P) production by CL cells obtained from patients at laparotomy. We first examined whether the CL produces IGF-I by measuring IGF-I levels in the ovarian vein from the ovary bearing the CL. The IGF-I concentration in the ovarian vein bearing the CL (206 +/- 31 ng/mL) was significantly increased compared to the concentration in the contralateral ovarian vein (179.2 +/- 32 ng/mL; P < 0.05). Luteal cells isolated from mid-CL were cultured in serum-free medium 199 in the presence and absence of hCG, FSH, GH, and graded concentrations of IGF-I. At the end of the incubation period (24 h), P levels in the medium were measured by RIA. The treatment with IGF-I (0.1-10 ng/mL) showed a dose-dependent stimulatory action of IGF-I on P synthesis in the luteal cell system, being maximal between 5-10 ng/mL. The treatment with hCG (10 IU/mL), IGF-I (5 ng/mL), and GH (1000 ng/mL) increased basal P synthesis by 300%, 80%, and 30%, respectively (P < 0.001 and P < 0.05). FSH (100 ng/mL), either alone or in combination with IGF-I, failed to stimulate P synthesis. Treatment with IGF-I monoclonal antibody (1:5000) completely reduced P synthesis induced by 5 ng/mL IGF-I and slightly reduced basal P synthesis as well as GH-stimulated P synthesis by human midluteal cells. To further evaluate the specific role of IGF-I on luteal steroidogenesis, IGF-I receptor was identified by chemical cross-linking of [125I]IGF-I to mid-CL membranes. Experiments conducted in the absence and presence of unlabeled IGF-I (500 ng) revealed proteins with characteristics of the type I IGF receptor. These results are consistent with multihormonal regulation of P synthesis by the human mid-CL. hCG and IGF-I play a major role in the stimulation of P synthesis and, to a lesser extent, human GH. These in vivo and in vitro data suggest that the CL is a site of secretion, action, and reception of IGF-I during the midluteal phase.

Adult↗

PubMed1995

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.

Adult↗

PubMed1994

Steroidogenic capacity and oxidative stress-related parameters in human luteal cell regression.

The steroidogenic capacity and oxidative stress-related parameters of the human corpus luteum (CL) at different stages of the luteal phase were studied under basal and human chorionic gonadotropin (hCG)-stimulated conditions. Mid CL exhibited the maximal steroidogenic capacity, together with lower levels of glutathione and higher thiobarbituric acid reactants content, macrophage count, and superoxide dismutase (SOD) activity, compared to the late CL. Addition of hCG to luteal cell cultures led to a preferential increase in progesterone synthesis in the late CL compared to the mid CL, without changes in the oxidative stress-related parameters, except for the increased SOD activity found in the late CL. It is concluded that an oxidative stress condition is established in the mid CL, coinciding with the maximal steroidogenic capacity and macrophage infiltration of the organ, which may be of relevance as one of the major mechanisms initiating CL involution in the human.

Adult↗

PubMed1994

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.

Adolescent↗

PubMed1994

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.

Adult↗

PubMed1994

Progesterone synthesis by human luteal cells: modulation by estradiol.

To assess the role of estradiol (E2) upon progesterone (P4) synthesis, a well defined human midluteal cell system was used. A dose-dependent inhibition of P4 synthesis with and without hCG was induced by E2. In addition, E2 had a dose related cumulative effect on pregnenolone as compared with control experiments (2-fold, P < 0.05) as well as in hCG-stimulated conditions (3-fold, P < 0.005). On the other hand, the concentrations of 20 alpha-hydroxyprogesterone obtained in all experimental conditions were similar to control values, indicating that the catabolism of P4 was not modified. 3 beta-Hydroxysteroid dehydrogenase activity was significantly diminished (P < 0.05) in the presence of E2. Finally, the kinetic studies on P4 synthesis from pregnenolone showed a competitive type of inhibition with a K1 of 2.22 x 10(-6) mol/L. These data indicate an inhibition of 3 beta-hydroxysteroid dehydrogenase on human corpus luteum by E2.

20-alpha-Dihydroprogesterone↗

PubMed1994

[Effect of chronic blockade of the opiodergic receptor on insulin resistance in a hyperandrogenic woman].

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.

Acanthosis Nigricans↗