Basal LH Levels Research Articles

Differential inhibition of NMDA- and naloxone-induced LH release by NMDA receptor antagonist and CRH in ovariectomized estrogen-primed rats.

A possible functional relationship between endogenous opioid peptides (EOPs), corticotropin-releasing hormone (CRH) and excitatory amino acids (EAAs) in the control of LH secretion was investigated in ovariectomized estrogen-primed rats. An intraventricular (icv) injection of an EAA agonist, N-methyl-D-aspartate (NMDA), or an EOP antagonist, naloxone, produced an abrupt increase in the serum LH level. While icv pretreatment of the animals with 2-amino-5-phosphonovaleric acid, a specific NMDA receptor antagonist, did not affect by itself basal LH levels, it significantly suppressed the NMDA-induced and also the naloxone-induced LH release. An icv injection of CRH also interfered with the naloxone-induced LH release. However, the NMDA-induced LH release was not affected by an icv injection of CRH or of beta-endorphin. These results suggest that the sites of EOP and CRH inhibition may be located upstream of the site of NMDA stimulation on the GnRH neuronal pathway, and that CRH can inhibit LH secretion without mediation by EOP neurons.

Regulation of gonadotropins and parathyroid hormone by nitric oxide

Nitric oxide has been recently recognized as an intra- and inter-cellular messenger. Animal studies have suggested a role for nitric oxide in the regulation of gonadotropin secretion. In this study of 14 healthy, young males, nitroglycerine administered sublingually was demonstrated to inhibit GnRH stimulated LH secretion from the pituitary (p < 0.05). There was no significant effect on GnRH stimulated FSH secretion. Nitroglycerine increased basal PTH levels (< 0.02), but had no significant effect on basal LH, FSH, TSH, cortisol, calcium, or prolactin levels. This study presents evidence that nitric oxiaϵ modulates LH and PTH secretion in humans.

Roles of inhibin and estradiol in the regulation of follicle-stimulating hormone and luteinizing hormone secretion during the estrous cycle of the rat.

The relative contributions of inhibin and estradiol in the regulation of FSH and LH secretion were examined at various stages of the estrous cycle in the rat. At 1100 h on metestrus, diestrus, or estrus or at 0500 h on proestrus, rats were ovariectomized or given an injection of normal goat serum, antiserum to inhibin (inhibin-AS), antiserum to estradiol (estradiol-AS), or both antisera to examine the role of gonadal hormones in the regulation of tonic gonadotropin secretion. Plasma samples were collected before and at 6, 12, and 24 h after the treatments. Further, to examine the effects of the treatments on preovulatory gonadotropin surges, the five treatments described were carried out at 0500 h on proestrus and blood samples were collected from 1100 h to 2000 h on the same day at 1.5-h intervals. There was a significant rise in the concentration of plasma FSH after injection of inhibin-AS as well as after ovariectomy on each day of the estrous cycle. These treatments, however, had less effect on estrous FSH secretion. The rise in FSH was greater with immunoneutralization against both inhibin and estradiol than with immunoneutralization against inhibin alone on diestrus and proestrus. Basal levels of LH were increased at all stages of the cycle through immunoneutralization against inhibin and were also increased through immunoneutralization against estradiol except at estrus. Especially on diestrus, a remarkable increase in LH secretion was induced at 6 h after immunoneutralization against both inhibin and estradiol (1449.3 +/- 100.3% vs. control). The magnitude of the LH surge increased in inhibin-immunized rats, decreased in estradiol-immunized or ovariectomized rats, and remained at normal levels after injections of both antisera. The magnitude of the primary FSH surge increased very markedly in the inhibin-immunized group and decreased in the estradiol-immunized group. These results suggest that both estradiol and inhibin play a role in the regulation of LH secretion and that inhibin is a major regulator of FSH secretion during the estrous cycle of the rat. Furthermore, it is suggested that one or more extragonadal factors suppress estrous FSH secretion.

Hormonal function of sexual glands and adrenals in monkeys of different age

The levels of bioactive LH, major sex and adrenal steroid hormones and their precursors in the system of biosynthesis were measured in the peripheral blood of 37 male Papio hamadryas of different age under baseline conditions and after injection of ACTH, LH releasing hormone, and human chorionic gonadotropin. The measurements were carried out in adult animals with the optimal reproductive characteristics (group 1, aged 6 to 9, and group 2, aged 10 to 15 years) and in aging males (group 3, aged 20 to 26 years). The levels of hydrocortisone and its immediate precursor in the biosynthesis chain of 11-deoxyhydrocortisone virtually did not change with age, whereas the concentrations of ∆5-precursors (pregnenolone and 17-hydroxypregnenolone) gradually reduced with aging. The levels of the major adrenal androgens dehydroepiandrosterone and dehydroepiandrosterone sulfate also appreciably decreased with age. The levels of sex hormones did not change between 6 and 15 years of age; but in animals aged 20 to 26 the concentration of testosterone showed a trend to reduction, and that of LH to increase. In group 3 the peaks of LH and testosterone secretion in response to LH releasing factor were delayed. On the other hand, the amplitude and duration of the increment of both LH and testosterone in response to LH releasing factor was virtually unchanged at all ages and was largely determined by the basal level of LH. The detected age-specific changes in the hormonal function of adrenals and sex glands of Papio hamadryas are much similar to those in humans.

Value of buserelin testing in the evaluation of hirsute women.

It has been recently reported that many hirsute women are affected with functional ovarian hyperandrogenism (FOH)-a term that encompasses the heterogeneous polycystic ovary syndrome- and show an abnormal ovarian steroidogenic response to gonadotropin-releasing hormone (Gn-RH) agonists. The aims of the present study were to determine the prevalence of FOH by the assessment of 17-hydroxyprogesterone (17-OHP) response to the Gn-RH agonist buserelin, to correlate these abnormal responses to other parameters suggestive of PCOS, and to assess the possible adrenal origin of hyperandrogenism. Therefore, in 33 consecutive women with hirsutism serum LH, FSH, 17-OHP, dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), cortisol levels were evaluated in basal conditions and after the administration of buserelin (0.5 mg sc) and ACTH (tetracosactide 0.25 mg iv). Two patients were affected with a non classic congenital adrenal hyperplasia (CAH)-21OH deficiency. In 5 other women ACTH test caused a rate increase 17-OHP (30-0)/30 min > 19 nmol/L/min (0.25 +/- 0.03; mean +/- SE), suggesting the possible existence of heterozygote non classic CAH-21OH. One patient showed a DHEA-S response to ACTH (from 10.3 to 17.2 mumol/L), which was compatible with late-onset 3 beta-Hydroxy-delta 5 steroid dehydrogenase deficiency. Out of the 25 patients with normal responsiveness to ACTH, 11 women (group A) showed higher 17-OHP and A levels, in comparison to normal women, both in basal conditions (17-OHP = 4.18 +/- 0.72 vs 1.74 +/- 0.34 nmol/L, p < 0.005; A = 11.8 +/- 1.2 vs 6.0 +/- 0.7 nmol/L, p < 0.05) and after buserelin (17-OHP = 15.61 +/- 1.31 vs 6.96 +/- 0.9 nmol/L; A = 19.0 +/- 1.9 vs 7.5 +/- 0.8 nmol/L; p < 0.001). In 6 of these 11 patients basal and buserelin-stimulated LH levels were higher than in normals. The remaining 14 patients (group B) showed normal baseline and buserelin-stimulated 17-OHP and A concentrations. In this group only 2 patients had high basal and stimulated LH levels. An augmented LH/FSH ratio was present in 5 and 1 cases of groups A and B, and polycystic ovaries at ultrasonography were observed in 7 and 8 cases of groups A and B, respectively. It is to note that an abnormal 17-OHP response to buserelin was present also in 3 of the 5 patients with abnormal 17-OHP rise after ACTH test, suggesting an adrenal and ovarian cause of hyperandrogenism. In conclusion, an abnormal response to one or both stimulation test was present in 57% of cases: an adrenal origin of hirsutism was detected in 15%, a combined adrenal and ovarian origin was found in 9% and an ovarian cause was present in 33%. Buserelin testing is an useful means to reveal the presence of FOH.

The corpus luteum insufficiency: a multifactorial disease.

The pulsatile release pattern of LH during the entire menstrual cycle is well defined; however, the response of corpora lutea to these LH pulses in patients suffering from corpus luteum insufficiencies (CLI) is largely unknown. Patients suffering from CLI were selected from infertile patients on the basis of low progesterone (P < 25 nmol/L) in a blood sample withdrawn during a monitoring cycle. During the next cycle, nine blood samples were collected during the follicular and luteal phase and follicular development was assessed by vaginal sonography. Of 109 patients who had a CLI in the monitoring cycle, 55 had a CLI again, and 38 women agreed to undergo assessment of pulsatile hormone secretion. These women again had P < 25 nmol/L at days 6 and 7 of the luteal phase and blood samples were withdrawn through antecubital vein catheters from 0900-1700 h at 10-min intervals on days 7, 8, or 9 following ovulation. From 38 patients with such defined CLI, 16 (42%) had no LH episode and significantly lower basal LH levels in comparison with 14 control subjects. Thirteen (34%) of the patients had normal appearing LH episodes despite too low P and E2 concentrations, but their CL did not react to the LH episodes. The remaining 9 patients (24%) had normal LH episodes; their CL reacted to these episodes, but their basal P levels were too low. In all blood samples LH was not only determined using an immunoassay but also by the mouse Leydig cell testosterone production bioassay. It could be established that no CLI exists, which is due to the release of bioinactive LH. It is anticipated that the differentiation of three different types of CLI, one of hypothalamic and two of ovarian origin, may allow the development of differential diagnostic and therapeutic tools in the future.

Hormonal Evaluation in Idiopathic Oligozoospermia: Correlation with Response to Clomiphene Citrate Therapy and Sperm Motility

The reported response of sperm count to clomiphene citrate therapy in subfertile males with idiopathic oligozoospermia has been widely variable. The author postulates that this may be due in part to patient heterogeneity that may be reflected in pretreatment hormonal status. Seventeen patients with idiopathic oligozoospermia (mean +/- SE sperm density of 7.3 +/- 1.2 x 10(6) sperm/mL, mean FSH of 5 +/- 0.5 IU/L) were studied. Pretreatment basal LH, FSH, testosterone, free T4, and prolactin levels as well as LHRH-stimulated LH and FSH levels were examined in relation to pretreatment semen parameters and percent change in sperm count after a mean of 7.2 +/- 0.6 months of clomiphene citrate therapy. The percentage of motile sperm correlated with basal LH (r = .59, p = .02, n = 16) and free T4 levels (r = .62, p = .02, n = 13). Clomiphene citrate therapy was associated with a significant increase in total sperm count (mean percent change 261 +/- 117, p = .02) and in total motile sperm count (mean percent change 370 +/- 216, p = .03). Percent change in total sperm counts and in total motile sperm counts correlated positively with pretreatment prolactin levels (r = .64, p = .007, n = 16, and r = .62, p = .01, n = 15), but not with the levels of other hormones. The results suggest that in patients with idiopathic oligozoospermia (1) clomiphene citrate therapy may be more effective in the subgroup of patients who have relatively higher prolactin levels, (2) basal and stimulated gonadotropin levels may not be helpful in predicting the response to clomiphene citrate therapy, and (3) lower sperm motility is associated with relatively higher free T4 and lower LH levels. The underlying mechanisms and the clinical utility of the current observations deserve further study.

Azoospermia: clinical, hormonal, and biochemical investigation.

The aim of this study was to evaluate the clinical, hormonal and biochemical characteristics of infertile men with azoospermia. A total of 187 azoospermic out of 2610 infertile men (7.2%) were studied. Mean testicular volume and basal plasma levels of FSH were the most useful parameters concerning the evaluation of azoospermia. Basal plasma levels of LH and T were useful only in azoospermic men with hypogonadism, whereas plasma PRL levels, semen volume, and seminal plasma fructose levels were not found to be of common use except in selected cases.

A Case of Pituitary Abscess with Masked Diabetes Insipidus following Bacterial Meningitis

A 37-year-old woman was admitted to our institution because of bacterial meningitis with hyponatremia (121mEq/L). Brain magnetic resonance imaging disclosed a cystic mass extending from the intra sellar to suprasellar regions in a T1 weighted image. Basal plasma levels of LH, FSH, ACTH and cortisol were lower than normal range. The plasma levels of ACTH and cortisol were relatively low during the insulin-stress test. During the intravenous administration of LH-RH and CRH, while ACTH and cortisol increased within the normal range, those of LH and FSH did not. Treatment with hydrocortisone produced a rapid normalization of the serum levels of sodium. However, this treatment led to polyuria with hyposthenuria. Saline (5%) infusion and water loading tests were carried out with or without the administration of oral hydrocortisone (60mg/day). The plasma ADH did not decrease during the water loading test without hydrocortisone, whereas the urinary osmolality value was higher than that observed in the serum. On the other hand, during the saline (5%) infusion test with hydrocortisone, the plasma level of ADH did not increase, and the urinary osmolality value was lower than that observed in the serum. Based on the clinical and histological findings, the diagnosis of pituitary abscess associated with partial hypopituitarism and masked diabetes insipidus were done. From the results of the insulin-stress and CRH tests, the coexistence of hypothalamic dysfunction was also suspected. This is a rare and interesting case of hypopituitarism with masked diabetes insipidus resulting probably from bacterial meningitis and pituitary abscess.

Studies on the cytogenetic and endocrinologic background of spontaneous abortion

To determine whether chronic menstrual irregularity with elevated LH levels has a role in spontaneous abortion. In 41 consecutively examined women with spontaneous abortions occurring within 11 complete gestational weeks, fetal chromosomal analyses were performed. The differences of endocrinologic background in relation to the result of fetal chromosomal analyses were investigated. Endocrinologic profiles, including menstrual history, basal hormone levels (LH, FSH, and PRL), ovarian morphology on ultrasound, and fetal chromosomal karyotypes. The women with normal fetal karyotypes compared with those with abnormal fetal karyotypes showed higher frequency of menstrual irregularity (47.1% versus 8.3%), elevated basal LH levels (7.42 +/- 5.12 versus 4.41 +/- 1.39 mIU/mL; conversion factor to SI unit, 1.00), and higher frequency of polycystic ovary (41.2% versus 8.3%). Elevated LH-polycystic ovary may be involved in the genesis of spontaneous abortions that are not explainable by fetal chromosomal abnormality.

Effects of prenatal exposure to delta-9-tetrahydrocannabinol on reproductive, endocrine and immune parameters of male and female rat offspring

The effects of prenatal THC administration, given during the third week of gestation in rats, on the reproductive, endocrine and immune systems of the adult offspring were examined. THC treatment blocked the surge of testosterone which occurs in the male rat fetus on gestation day 18. Moreover, when copulatory parameters were measured in adult male offspring, males that had been exposed to THCin utero exhibited an increased latency to mount (THC: 245±49vs vehicle: 99±12 sec) and none of the males ejaculated. Female rats exposed to THCin utero, exhibited an increased incidence of irregular estrous cycles and the number of females exhibiting lordosis behavior was reduced when compared to vehicle controls. Hormone analyses revealed that prolactin levels were significantly lower in the THC-vs vehicle-exposed male (THC: 5.2±0.4vs vehicle: 8.4±0.6 ng/ml) and female offspring (THC: 5.7±0.3vs vehicle: 12.2±1.8 ng/ml). However, there were no significant differences in basal plasma LH levels or in testicular weights of the male offspring. Thymus weight and total number of thymocytes were significantly higher in THC-exposed male and female rats when compared to vehicle controls. Together, these results indicate that maternal THC exposure has long-lasting effects on reproductive, endocrine and immune parameters of both male and female rat offspring.

Effect of laparoscopic ovarian electrocautery on ovarian response and outcome of treatment with gonadotropins in clomiphene citrate-resistant patients with polycystic ovary syndrome

To evaluate the effect of ovarian electrocautery on the ovarian response to gonadotropic stimulation and pregnancy rate (PR) in clomiphene citrate (CC)-resistant women with polycystic ovary syndrome (PCOS) and high basal serum LH levels. Retrospective study. Outpatient infertility clinic in a tertiary referral center. Twenty-two women with PCOS, high basal serum LH concentrations, and CC resistance who underwent laparoscopic ovarian electrocautery. Treatment with gonadotropin was scheduled after failure to ovulate spontaneously or conceive after electrocautery. Data from gonadotropin-stimulated cycles were compared with data from treatment cycles in the same patients before ovarian electrocautery. Number of ampules, duration of induction phase, daily effective dose, PR, and pregnancy outcome. Markedly reduced basal serum LH concentrations and normal menstrual cyclicity in 41% of patients were recorded after laparoscopic ovarian electrocautery. Comparison of gonadotropin-stimulated cycles before and after electrocautery revealed significantly higher rates of ovulation and pregnancy after electrocautery as well as significant reduction in the number of ampules, daily effective dose, and duration of the induction phase with hMG and in daily effective dose with FSH. Our results indicate an increased ovarian sensitivity to gonadotropins after laparoscopic ovarian electrocautery. A preference for laparoscopic ovarian electrocautery over medical treatment in all or selected groups of CC-resistant PCOS patients is suggested.

Dopaminergic inhibition of pulsatile luteinizing hormone secretion is abnormal in regularly menstruating women with insulin-dependent diabetes mellitus

To examine the influence of low doses of dopamine (DA) (0.4 micrograms/kg per minute), on the secretion pattern of LH. Prospective randomized, single blind, placebo-controlled crossover study with infusion of DA or placebo in the follicular phase in regularly menstruating women with insulin-dependent diabetic mellitus (IDDM) and controls during 9.5 hours. Department of Endocrinology, Odense University Hospital, Odense, Denmark. Eight regularly menstruating IDDM women and eight controls. Mean LH, LH pulse amplitude, and LH pulse frequency. During placebo infusion no significant differences in basal LH values, pulse amplitude, and pulse frequency were seen between IDDM women and controls. In diabetics, basal LH levels and pulse amplitude decreased significantly during DA infusion (3.1 +/- 1.2 mIU/mL (conversion factor to SI unit, 1.00; mean +/- SD) and 0.9 +/- 0.3 mIU/mL, respectively) compared with placebo (4.5 +/- 1.1 and 1.2 +/- 0.4 mIU/mL, respectively). In normal women no significant changes were observed (basal LH 3.0 +/- 1.8 versus 3.2 +/- 1.6 mIU/mL and pulse amplitude 1.6 +/- 0.6 versus 1.5 +/- 0.9 mIU/mL). The LH pulse frequency during DA infusion was not different from placebo in either normal (9.0 +/- 2.7 versus 10.3 +/- 4.0) or diabetic women (11.8 +/- 2.1 versus 10.9 +/- 1.8). These results suggest that diabetic women are more sensitive to a small increase in peripheral DA concentration. An abnormal permeability of the blood-brain barrier in IDDM patients could explain a greater exposure of the hypothalamic structures, regulating the pituitary gonadotropin hormone secretion.

Alterations in hypophysial responsiveness to synthetic GnRH at different postpartum intervals in Murrah buffalo ( [formula omitted

The objective of this study was to investigate the hypophysial responsiveness to GnRH at different intervals post partum in Murrah buffalo. Plasma LH and FSH levels were measured at 1 h before and upto 6 h subsequent to the administration of GnRH (1 ug/kg body weight) or saline on Days 2, 20 and 35 post partum in 2 groups of buffalo (n=4 each). Plasma progesterone levels were measured in samples collected once daily from Day 3 to Day 46 post partum. Pretreatment basal LH levels exhibited a progressive increase from Day 2 through Day 35 post partum, while the basal FSH levels increased only until Day 20 post partum. Following a highly subdued LH response to GnRH on Day 2 post partum, a 408% increase (P < 0.01) was observed in the total LH released in response to GnRH on Day 20 post partum, followed by a 20% reduction (non-significant) over Days 20 to 35 post partum. The interval from parturition was highly correlated with total LH released (r = 0.711, P < 0.01). Unlike LH, a substantial amount of FSH was released following GnRH treatment on Day 2 post partum, which was not significantly different from the FSH response on Days 20 and 35 post partum. The LH and FSH response to GnRH was not significantly different between animals in which luteal activity resumed and in those which showed no luteal activity post partum. While pointing to a dramatic enhancement in the hypophysial responsiveness to GnRH between Days 2 and 20 post partum, these results suggest that pituitary responsiveness to GnRH does not appear to be the limiting factor for resumption of estrous cycles by Day 35 post partum in Murrah buffalo.

Male gonadal function after chemotherapy in survivors of childhood malignancy.

Investigations of adult patients have shown that chemotherapy causes gonadal damage, but much less information is available about the impact of chemotherapy on gonadal function in children with malignant disease. At one time, being prepubertal during therapy was thought to confer some protection against chemotherapy induced gonadal damage. However, recent studies have indicated otherwise. We designed this study to assess gonadal function in 15 postpubertal males who had received polychemotherapy for a malignant disease during childhood and we compared them with 13 control adults males. The mean age of the patients at the time of the study was 18.2 +/- 3.6 years (range 13.8-29.0), and when given chemotherapy treatment was 10.2 +/- 3.0 years (range 6-16). At that time 12 were prepubertal and at the time of the study all were Tanner V. The mean interval from the completion of treatment until the study was 6.42 years (range 2.0-16.5). All patients had received polychemotherapy. We evaluated testicular size, sperm counts, LH and FSH after GnRH test, and testosterone levels. Puberty had progressed normally in all patients. We found no significant differences in testosterone and basal LH levels between patients and controls. However, we detected an appreciable difference in peak LH levels (P < 0.05) and in basal and peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH, indicating dysfunction of the Leydig cells. The results of semen analyses were: 8 patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen analysis. All patients with semen abnormalities presented a basal and peak FSH higher than the mean +2 SD of the control group. In summary, we found no evidence of gonadal protection in prepubertal patients. We found a high incidence of germinal cell damage, whereas Leydig cell abnormalities were found less often. An endocrine study of patients that have received chemotherapy is warranted.

Antiovulatory actions of RU 486: the pituitary is not the primary site of action in vivo.

Continuous administration of RU 486 impairs follicular development and inhibits ovulation in women. Yet, the mechanism of ovulation inhibition remains unknown. To characterize the mechanism(s) of ovulation inhibition, we studied six regularly menstruating cynomolgus monkeys for three consecutive (control-rest-treatment) cycles. Monkeys received 1 mg/kg.day RU 486 in between cycle days 2-22. Basal and GnRH-stimulated (1 and 50 micrograms GnRH, iv, 2 h apart) secretion of LH and FSH was assessed using serial blood samples (every 15 min for 12 h) collected on cycle day 10. Serum levels of estradiol (E2), progesterone (P4), RU 486, cortisol, LH, FSH, and PRL were analyzed by RIAs, the bioactivity of LH was assessed using a mouse Leydig cell assay. The mean cycle length was prolonged by RU 486 treatment from 31.8 to 69.8 days (P = 0.008). During RU 486 treatment, patterns of E2 secretion varied considerably; the mean +/- SD E2 level was 204 +/- 139 pmol/L. LH peaks and P4 profiles compatible with luteal function were seen only before resumption of menstruation. However, one monkey had an increase in P4 after the GnRH challenge-induced LH secretion. Basal levels of LH varied between suppressed and apparently normal values, whereas basal FSH seemed little affected by RU 486 treatment. In two monkeys with E2 secretion indicative of normal follicular development, minor peaks of LH, but no rises in serum P4, were seen. The ratio of bioactive/immunoactive LH was reduced in these monkeys during RU 486 treatment compared to that during the washout period of the treatment cycle. Surprisingly, the pituitary responsiveness to acute GnRH challenge was not affected by RU 486 administration. The individual levels of RU 486 were similar during the treatment period (mean, 40 nmol/L). A resumption of ovulatory cycles occurred when RU 486 concentrations were below 2.5 nmol/L. We conclude that in cynomolgus monkeys, inhibition of ovulation by RU 486 occurs mainly at the level of the hypothalamus, with possible additional effects on the granulosa cell function and alterations of LH bioactivity.

Evidence that hypothalamic neuropeptide Y gene expression increases before the onset of the preovulatory LH surge.

Neuropeptide Y (NPY), a 36 amino acid residue peptide, is involved in stimulation of LHRH and LH surges on proestrus and those induced by ovarian steroids in ovariectomized (ovx) rats. Recently, we observed that NPY gene expression in the medial basal hypothalamus (MBH) was increased before the onset of the LH surge in the ovarian steroid-primed ovx rats. Since the ovarian steroidal milieu during the estrous cycle is markedly different from that prevailing after ovarian steroid injections in ovx rats, we evaluated in cycling rats the temporal relationship between MBH preproNPY mRNA levels and the preovulatory LH surge on the day of proestrus and compared that with diestrus II, concomitant with basal LH levels. PreproNPY mRNA levels in the MBH were measured by solution hybridization/RNAse protection assay, using a cRNA probe. On the day of diestrus II, preproNPY mRNA levels changed little between 1000 and 1800 h. Quite unexpectedly, preproNPY mRNA levels at 1000 h on proestrus were similar to diestrus II levels, despite additional exposure to ovarian steroids during this interval. However, from these low levels at 1000 h, the preproNPY mRNA profile displayed a biphasic rise. During the first phase, preproNPY mRNA rose significantly at 1200 h and remained elevated at 1300 and 1400 h concomitant with basal serum LH levels. Thereafter, a second rise in preproNPY mRNA began at 1500 h, peaked rapidly at 1600 h and declined significantly at 1800 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Ovarian Stromal Hypertrophy in Hyperandrogenic Women

Dewailly, Didier; Robert, Yann; Helin, Isabelle; Ardaens, Yves; Thomas-Desrousseaux, Patricia; Lemaitre, Laurent; Fossati, PierreAuthor Information

Disturbance of follicular development and endocrine reactions induced by the antiovulatory effective progesterone antagonist Onapristone

The present study was undertaken to investigate whether inhibition of ovulation, which is known to occur after treatment with progesterone antagonists, is due to the effect of high levels of prolactin. Therefore, rats with 4-day cycles were treated with the antiprogestin, Onapristone (ON), once daily starting on the evening of estrus. It was detected that the profile of peripheral prolactin levels during the treatment with ON was not remarkably different from that found in the controls. Furthermore, bromocriptine, a prolactin antagonist, was not able to reverse the antiovulatory potency of ON. It is concluded that the antiovulatory effect of ON might not be related to changes in the level of prolactin. Nevertheless, prolactin levels remained high after the preovulatory surge. Thus, we cannot exclude the possibility that PRL plays a role in the induction of anovulatory cycles observed during long term treatment. In animals treated for the length of one cycle we found that the preovulatory LH surge decreased but it remains questionable whether this contributes to the inhibition of ovulation by ON. Interestingly, basal LH, androgen and estrogen levels were elevated. Accordingly, we favour the idea that LH stimulates the theca interstitial cells to produce excessive amounts of androgens which may be aromatized into estrogens. These high levels of androgens and estrogens may contribute to the antiovulatory mechanism of ON by disturbing physiological follicular development. In fact, a morphometrical analysis revealed an increase in the volume density of late tertiary follicles. The increased progesterone levels may also be related to high basal LH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Unconsciousness due to Hyponatremia in a Patient of Short Stature with Panhypopituitarism

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.