Measurement of the testosterone binding parameters for both testosterone-estradiol binding globulin and albumin in individual serum samples

This report describes a solid phase method for the characterization of testosterone binding to both albumin and testosterone-estradiol binding globulin (TeBG). TeBG is adsorbed from serum samples onto a solid phase matrix of concanavalin A covalently linked to 4B Sepharose. The binding of testosterone is then examined both in the presence and absence of the endogenous serum albumin. Analysis of the resulting Scatchard plots permits determination of the TeBG binding capacity, TeBG association constant and a parameter of albumin binding equivalent to the product of its affinity and capacity for binding testosterone. Results showed that the TeBG capacity was lower in men than in women (18.4 +/- 5.8 vs. 33.1 +/- 19.2 nM, p less than 0.01). The association constant was greater in men (1.59 +/- 0.35 vs. 1.19 +/- 0.32 x 10(9)M-1, 10(9)M-1, p less than 0.01). There was no difference in the albumin binding parameter (43.8 +/- 18.3 vs. 46.6 +/- 15.5, NS). These parameters can then be used to calculate the distribution of the circulating testosterone into albumin bound, TeBG bound and unbound fractions.     

Site of negative feedback action of estrogen on gonadotropin secretion in normal women

We have reported that iv administration of conjugated estrogens results in no significant change in the plasma LH-RH level during the negative feedback phase of LH, suggesting that estrogen does not suppress LH by decreasing hypothalamic LH-RH. To determine the site of estrogen action during the negative feedback phase, we studied the pituitary response to a small amount of LH-RH after estrogen administration in normal cyclic women in the mid-follicular phase. The pituitary responses to an iv bolus of 2.5 micrograms of synthetic LH-RH were evaluated by measuring serum LH and FSH 2 h before and 8 h after administration of 20 mg of conjugated estrogens (Premarin). The mean levels of serum LH and FSH were significantly (p less than 0.05) decreased 8 h after the injection. The peak responses of LH and FSH to LH-RH were also significantly (p less than 0.05) reduced after Premarin administration. These findings suggest that the negative feedback effect of estrogen on gonadotropin secretion is caused by its direct suppression on the pituitary response to LH-RH.     

Plasma gonadotropins and prolactin in pseudopregnancy in the rat

Radioimmunoassay presented a method of measuring plasma levels of FSH,LH and prolactin in pseudopregnant rats. Plasma prolactin levels doubled 15 minutes following cervical probing (p .01) on the day of estrus. Plasma LH levels were not significantly elevated. Due to the use of ether anesthesia at blood collecting 3 hr before and 15 minutes after stimulation, only 1 of 16 rats developed pseudopregnancy. On Day 4 of pseudopregnancy in rats mated with vasectomized males; plasma LH was lower (p .05) than in normal rats on the first day of diestrus, perhaps due to the suppressive action of ovarian progesterone and some estrogen. FSH was higher than in normal rats (p .05) perhaps due to the lesser sensitivity of FSH to the inhibitory effect of progesterone. Large decidoumata developed by Day 9 in uterine horns traumatized on Day 4 (153 plus or minus 8 mg uterus weight compared to 1510 plus or minus 204 mg). Thus, the corpora remain functional after LH and prolactin are at normal and subnormal levels. On Day 9 plasma prolactin was lower than at Day 1 of diestrus (p .001). Plasma FSH was elevated (p .01). Plasma LH was unchanged. The degree of rise of LH levels 5 days following ovariectomy on Day 4 of psuedopregnancy or on the first day of diestrus was greater in the former group (p .02), perhaps due to rebound of LH from suppression by ovarian steroids. FSH rose equally in both groups. Prolactin remain about the same. Increased prolactin release by the adenohypophysis was briefer than expected.     

Autocrine role of estrogens in the augmentation of luteinizing hormone receptor formation in cultured rat granulosa cells

The effects of estrogens on gonadotropin-stimulated luteinizing hormone (LH) receptor formation were examined in primary cultures of rat granulosa cells. Granulosa cells were cultured for 3 days with increasing concentrations of follicle-stimulating hormone (FSH) in the presence or absence of native and synthetic estrogens. Follicle-stimulating hormone stimulated LH receptor formation in a dose-dependent fashion, and estrogens enhanced the FSH-stimulated LH receptor content by decreasing the apparent ED50 of FSH. At 6.25 ng/ml FSH, the enhancement in LH receptor was estrogen dose dependent, with an ED50 value of about 3 X 10(-9) M for 17 beta-estradiol. The increased LH receptor content seen in cells treated with FSH and estrogen was correlated with increased cAMP production by these cells in response to LH stimulation. Time course studies revealed enhancement of FSH-stimulated LH receptor induction at 48 and 72 h of culture. Granulosa cells were also cultured with FSH for 2 days to induce functional LH receptors, then further cultured for 3 days with LH in the presence or absence of estrogens. At 30 ng/ml LH, increasing concentrations of estrogens maintained LH receptor content in a dose-dependent fashion, with their relative estrogenic potencies in keeping with reported binding affinities to estrogen receptors. An autocrine role of estrogens on LH receptor formation was further tested in granulosa cells treated with FSH and an aromatase substrate (androstenedione) to increase estrogen biosynthesis. Cotreatment with semipurified estrogen antibodies partially blocked the FSH stimulation of LH receptors, whereas nonimmune serum was ineffective. Also, inclusion of diethylstilbestrol prevented the inhibitory effect of the estrogen antibodies. Thus, local estrogens in ovarian follicles may play an autocrine role in granulosa cells to enhance LH receptor formation and to increase granulosa cell responsiveness to the LH surge, with subsequent ovulation and adequate corpus luteum formation.     

Solid phase method for measurement of the binding capacity of testosterone-estradiol binding globulin in human serum

A solid phase method for measuring the binding capacity of serum testosterone-estradiol binding globulin (TeBG) is described and compared with other methods. TeBG, a glycoprotein, is adsorbed from serum or plasma onto a solid phase matrix of concanavalin-A, a carbohydrate-specific adsorbent. The TeBG binding capacity is determined by Scatchard analysis of the binding of radioactive testosterone at physiologic pH, in standard test tubes, and without the addition of albumin. Transcortin binding of testosterone is inhibited by the addition of cortisol.The levels of TeBG binding capacity determined with this solid phase method showed an excellent correlation with levels determined by procedures using equilibrium dialysis (with added cortisol) or ammonium sulphate precipitation. The serum TeBG binding capacity was 0.798±0.064 (mean±SE) μg/100 mL in men (n=32), 1.06±0.13 in women (n=10), 2.18±0.19 in women taking oral contraceptives (n=4), 6.2±2.9 in hyperthyroid women (n=2), and 11.6±3.1 in pregnant women (n=5). The serum TeBG binding capacity determined in heparinized plasma did not differ from that determined in serum. The within-assay variation is 9.6% and the between-assay variation is 11.2%.This solid phase method for measurement of serum TeBG binding capacity is simple, precise, and reproducible, and gives values which correlate well with those determined by other methods.     

Effect of administration of an alpha 2-adrenergic agonist, xylazine, on pulsatile gonadotrophin secretion in anoestrous horse mares

Two experiments were performed to test the hypothesis that the seasonal suppression of gonadotrophin pulse frequency in anoestrous horse mares reflects inhibitory neural mechanisms. In a preliminary experiment (Exp. 1) conducted in February, 4 anoestrous mares were sedated by repeated intravenous injections of xylazine, an alpha 2-adrenergic receptor agonist. On the day of treatment, 1-2 LH pulses were observed in xylazine-treated mares. In contrast, during a 12-h period only 1/8 untreated control mares exhibited a LH pulse. In Exp. 2, the effect of xylazine-induced sedation on pulsatile gonadotrophin release was examined in 4 anoestrous mares on two occasions before (18 November and 9 December) and after (23 December and 6 January) an abrupt, artificial increase in day length. Treatment with xylazine was associated with an overall increased FSH (P less than 0.01) and LH (P less than 0.05) pulse frequency, compared with that observed during 12-h pretreatment periods. To evaluate an effect of treatment at the various time during the experimental period, the change in FSH pulse frequency was analysed, since occasionally FSH pulses were unaccompanied by a change in serum LH values indicative of a LH pulse. On two occasions before increased daylength only 1/4 and 3/4 mares exhibited an increase in FSH pulses; in contrast, 14 days after increased daylength (23 December), 4/4 mares exhibited increased FSH pulse frequency associated with treatment. After 27 days of increased daylength (6 January), endogenous FSH pulse frequency was greater than before increased daylength and treatment with xylazine was unaccompanied by a further increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Temporal relations between plasma concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol-17beta, progesterone, prolactin, and alpha-melanocyte-stimulating hormone during the follicular, ovulatory, and early luteal phase in the bitch

Compared with other domestic animals, relatively little is known about the changes in, and temporal relations between, reproductive hormones around the time of ovulation in the domestic bitch. Therefore, plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol-17beta, progesterone, prolactin (PRL), and alpha-melanocyte-stimulating hormone (alpha-MSH) were determined one to six times daily from the start of the follicular phase until 5 days after the estimated day of ovulation in six Beagle bitches. In all bitches, the pre-ovulatory LH surge was accompanied by a pre-ovulatory FSH surge. A pre-ovulatory PRL or alpha-MSH surge was not observed. The pre-ovulatory FSH and LH surges started concomitantly in four bitches, but in two bitches the FSH surge started 12 h earlier than the LH surge. The FSH surge (110+/-8 h) lasted significantly longer than the LH surge (36+/-5 h). In contrast with the pre-ovulatory FSH surge, the pre-ovulatory LH surge was bifurcated in four of six bitches. The mean plasma LH concentrations before (1.9+/-0.4 microg/L) and after (1.9+/-0.3 microg/L) the LH surge were similar, but the mean plasma FSH concentration before the FSH surge (1.6+/-0.3 U/L) was significantly lower than that after the FSH surge (3.1+/-0.2 U/L). In most bitches the highest plasma estradiol-17beta concentration coincided with or followed the start of the pre-ovulatory LH surge. In five of the six bitches the plasma progesterone concentration started to rise just before or concurrently with the start of the LH surge. In conclusion, the results of this study provide evidence for the differential regulation of the secretion of LH and FSH in the bitch. In addition, the interrelationship of the plasma profiles of estradiol-17beta and LH suggests a positive feedback effect of estradiol-17beta on LH surge release. The start of the pre-ovulatory LH surge is associated with an increase in the plasma progesterone concentration in this species.     

Dissociation of LH and FSH Responses to LHRH during estrogen therapy of patients with ovarian failure

This study examines the effect of oral estrogen treatment on gonadotropin secretion in three young women with gonadal failure. Each subject was treated with 0.1 mg BID of ethinyl estradiol for four weeks, and the LH and FSH responses to 200 microgram of intravenously administered LHRH were measured basally and weekly during therapy. Significant reduction of basal levels of FSH occurred within one week of treatment, with obliteration of LHRH-mediated FSH responsiveness within two weeks. By contrast, basal levels of LH were significantly reduced by the end of the second week of treatment, and LHRH-mediated LH levels were sustained for three weeks. In one subject an LHRH test was performed every other day for two weeks after cessation of therapy. Return of FSH responsiveness was delayed one week beyond that of LH, which occurred within three days of discontinuation of estrogen. These results indicate that during the early phase of oral estrogen replacement therapy, FSH secretion may be selectively blunted; after discontinuation of treatment, recovery of FSH secretion lags behind recovery of LH.     

Plasma follicle stimulating hormone in Merino ewes immunized with an inhibin-enriched fraction from bovine follicular fluid

Plasma FSH concentrations were measured in Merino ewes immunized with either an inhibin-enriched preparation from bovine follicular fluid (bFFI) or bovine serum albumin. When compared during the normal oestrous cycle, ewes reimmunized three times with bFFI and which showed increased ovulation rates before the experiment had significantly elevated plasma FSH concentrations on Day 13–14 and at Day 2 of the subsequent cycle. There was a positive correlation (P < 0.05) between plasma FSH concentration and the ovulation rate of the ewes in previous cycles (during the period of immunization) and in the cycle under investigation. In a larger group of ewes immunized against bFFI, which showed a variable increase in ovulation rate, there was no comparable increase in plasma FSH concentration when compared with control ewes in the follicular phase of the cycle.By contrast, when luteolysis was induced by a prostaglandin analogue the bFFI-immunized ewes had lower plasma FSH concentrations than control ewes immediately before and after the preovulatory LH surge. This decrease was significant in the period 9–21 h after the LH surge (P < 0.05–0.01) so that the onset of the second FSH peak was delayed.When the ewes were ovariectomized, the post-castration rise in plasma FSH concentration (but not LH) was delayed for a period of 24 h in bFFI-immunized ewes relative to controls.These experiments show that immunization of ewes with an inhibin-like fraction of bFF does not lead to consistently elevated plasma FSH. However, such ewes have altered feedback regulation leading to differential responses of FSH to prostaglandin-induced luteolysis and to castration.     

Estimation of instantaneous secretory rates and intrinsic characteristics of luteinizing hormone secretion in women with Kallmann syndrome before and after estriol administration

Three Kallmann syndrome (KS) patients were examined to assess characteristics of LH response to GnRH bolus, with and without GnRH sensitization using Instantaneous Secretory Rate (ISR) computation before and after estriol treatment (60 days, 2 mg/day). Six healthy women were enrolled as controls and underwent GnRH bolus during the early follicular phase (days 3-5 of the menstrual cycle). After estriol treatment, the KS patients showed a higher LH response to GnRH bolus and similar LH pulse duration to healthy controls. These data support the hypothesis that the administration of weak estrogen improves LH response to GnRH in hypogonadotropic women with KS.     

The recovery of ovarian function during breast-feeding

The pattern of breast-feeding was daily recorded and the serum concentrations of prolactin (PRL), FSH, LH, estradiol (E2) and progesterone (prog) were measured at weekly intervals in 26 breast-feeding mothers from the time of delivery and up to the resumption of regular ovulation or to the end of the first postpartum year. Twelve postpartum non-breast-feeding women were similarly studied as controls. An algorithm was used to characterize ovulatory events into three types: the first, with evidence highly suggestive of normal ovulation (EHSO), the second, with evidence of probable ovulation (EPO) and the third with evidence indicating questionable ovulation or deficient corpus luteum function (QO/DCT). Pregnancy preceded the first menstruation in one woman in each of the breast-feeding and control groups. Of the 19 breast-feeding women who started to menstruate during the first postpartum year, five had EHSO, one had EPO, 5 had EQO/DCL and 7 had anovulatory (AO) menstruation. The corresponding figures in the 11 controls were 6, 2, 3 and 0. Pregnancy occurred before a second menstruation in one woman in both the study group and the controls. In 18 breast-feeding women observed, the second menstruation was preceded by EHSO in 7, by EPO in 3, by EQO/DCL in one and AO in 7. In 10 controls the corresponding figures were 7, 3, 0 and 0. Out of a total of 79 menstruations observed during breast-feeding the incidence of AO was 30% and of QO/DCL was 15%. In actively breast-feeding mothers, hyperprolactinemia persisted for more than 1 yr. However, menstruation and ovulation occasionally occurred before the drop of PRL to concentrations seen during the normal menstrual cycle. In the majority of women, low E2 levels were present during lactational amenorrhea, but with occasional spikes in some. A few women maintained somewhat high values of E2 for several weeks before the resumption of menstruation. The implications of these hormonal findings to the attempts to improve on the contraceptive effect of breast-feeding are discussed.     

Examination of the role of follicle stimulating hormone in estrogen biosynthesis in vivo and in vitro in the ovary of the cyclic hamster

The effect of neutralizing endogenous follicle stimulating hormone (FSH) or luteinizing hormone (LH) with specific antisera on the in vivo and in vitro synthesis of estrogen in the ovary of cycling hamster was studied. Neutralization of FSH or LH on proestrus resulted in a reduction in the estradiol concentration of the ovary on diestrus-2 and next proestrus, suggesting an impairment in follicular development. Injection of FSH antiserum at 0900 h of diestrus-2 significantly reduced the ovarian estradiol concentration within 6--7 h. Further, these ovaries on incubation with testosterone (T) in vitro at 1600 h of the same day or the next day synthesized significantly lower amounts of estradiol, compared to corresponding control ovaries. Although testosterone itself, in the absence of endogenous FSH, could stimulate estrogen synthesis to some extent, FSH had to be supplemented with T to restore estrogen synthesis to the level seen in control ovaries incubated with T. Lack of FSH thus appeared to affect the aromatization step in the estrogen biosynthetic pathway in the ovary of hamster on diestrus-2. In contrast to this, FSH antiserum given on the morning of proestrus had no effect on the in vivo and in vitro synthesis of estrogen, when examined 6--7 h later. The results suggest that there could be a difference in the need for FSH at different times of the cycle. Neutralization of LH either on diestrus-2 or proestrus resulted in a drastic reduction in estradiol concentration of the ovary. This block was at the level of androgen synthesis, since supplementing testerone alone in vitro could stimulate estrogen synthesis to a more or less similar extent as in the ovaries of control hamsters.     

Negative feedback effects of chlormadinone acetate and ethynylestradiol on gonadotropin secretion in patients with prostatic cancer and male rats

Serum LH and FSH levels were determined before and after LH-RH injection (100 micrograms, i.m.) in patients with prostatic cancer who were chronically treated with either chlormadinone acetate (CMA, 100 mg/day) or ethynylestradiol (EE, 1 mg/day). In patients treated with EE, the levels of serum LH and FSH before and after injection of LH-RH were significantly lower than those in controls. On the other hand in patients treated with CMA, the basal levels of serum gonadotropins did not differ from those in controls, and the increase in gonadotropin after LH-RH injection was comparable to that in controls. To examine the effects of these steroids on the hypothalamo-hypophysial axis in the regulation of gonadotropin secretion, CMA or EE was implanted in castrated male rats. CMA, EE or cholesterol (control) was implanted in the hypothalamic median eminence-arcuate nucleus region through a stainless doublecannula. EE implantation resulted in a 75% decrease in serum LH (p < 0.001) and a 38% decrease in serum FSH (p < 0.05) from the control levels on day 5 of implantation. On the other hand, CMA implantation induced a 33% decrease in serum LH (p < 0.05) from the control level on day 3 of implantation, but no significant change in serum FSH levels. The injection of 2 micrograms/kg of LH-RH on day 7 of implantation induced significant lowering of LH and FSH levels. There was no significant difference between serum levels of the hormones 20 min after LH-RH injection for these two groups and those for the control group. These studies suggest that EE has a potent negative feedback effect on both LH and FSH secretion, and that CMA has a mild negative feedback effect on LH secretion.     

Inhibitory effect of progesterone in the postcastration gonadotrophin rise in women

This study was designed to investigate the effects of progesterone on the gonadotrophin rise after bilateral salpingo-oophorectomy (BSO). Twenty-eight regularly menstruating women underwent hysterectomy and BSO during the follicular phase of the menstrual cycle. They were divided into 5 groups depending on the treatment after BSO. Plasma LH and FSH were studied serially for 14 days after BSO and the patterns of LH and FSH rises were contrasted to those observed in the control group which received neither progesterone nor estrogen. LH and FSH levels in the group which were given low dose progesterone only, rose consistently after BSO and these patterns were similar to those seen in the control group. However, the addition of estrogen reduced gonadotrophin rises significantly more than estrogen did alone. Further, the luteal phase level of progesterone solely has a suppressive effect on the gonadotrophin rises after BSO. Our observations suggest that synergism of progesterone with estrogen may exist in suppressing gonadotrophin secretion in the normal luteal phase and should help in understanding why gonadotrophin levels in the luteal phase are lower than those in the follicular phase of the menstrual cycle.     

Plasma concentration changes in LH and FSH following electrochemical stimulation of the medial preoptic are or dorsal anterior hypothalamic area of estrogen- or androgen-sterilized rats.

Plasma concentraption changes in luteinizing hormone (LH) and follicle stimulation hormone (FSH) following elctrochemical stimulation (ECS) of the medial preoptic area (MPOA) or dorsal anterior hypothalamic area (DAHA) of estrogen-or androgen-sterilized rats were compared with normal proestrous rats in which spontaneous gonadotropin surges had been blocked with Nembutal (control). ECS of control rats, AST, and ESR provoked marked increases in FSH by 120 minutes and peak levels by 180 minutes poststimulation. No differenses were seen when ESR of ASR plasma levels were compared with control values or to each other (ESR vs. ASR). DAHA-ECS did not provoke a marked LH rise in ASR and ESR. MPOA-ECS of control, ASR, and ESR resulted in the release of LH and FSH. FSH peaked in all groups at 240 minutes but at 120 and 180 minutes poststimulation plasma FSH levels were greater in ASR and ESR than controls. FSH in ESR was significantly higher (p. 05) at 120 and 240 minutes poststimulation. LH was elevated in all groups following MPOA-EDS but in ESR markedly greater LH levels were obtained at 60 and 180 minutes compared with controls or ASR. Preoptic stimulation of progesterone-treated ASR (P-ASR) did not induce greater release of FSH than in control, ASR, ESR, or P-ESR. Stimulation of P-ASR resulted in greater plasma LH rise by 60 minutes which was greater than ASR, P-ASR, ESR, or controls, followed by decreased levels to baseline in P-ESR. MPOA-ECS controls ovulated (8-13 eggs) whereas neither ASR nor ESR Fallopian tubes contained eggs the following morning. No DAHA-stimulated groups ovulated. All P-ASR but no P-ESR ovulated after MPOA-ECS. It is concluded that while exposure of neonatal female rats to estrogen renders them more sensitive than ASR to preoptic stimulation, the ovaries of these amimals are much less responsive to the gonadotropin released into plasma than are those of ASR or normal rats.     

腹腔镜下卵巢囊肿剥除术后缝合与电凝止血对卵巢功能的影响

目的:探究腹腔镜下卵巢囊肿剥除术后缝合与电凝止血对卵巢功能的影响。方法:选择2014年5月~2015年12月期间我院收治卵巢囊肿患者78例为研究对象,两组患者均行腹腔镜下卵巢囊肿剥除术,根据患者术中止血方式的不同将其分为观察组(41例)和对照组(37例);观察组术中采用双极电凝止血,对照组患者性术中采用缝合止血;观察并比较术后4周、12周两组患者促卵泡生长激素(FSH)、促黄体激素(LH)、雌二醇(E2)及窦状卵泡计数(Shape of sinus follicle count,AFC),对比两组术后12周卵巢功能恢复情况。结果:术后4周两组患者FSH、LH水平较术前升高,E2及AFC水平较术前降低,差异均有统计学意义(P0.05);术后12周对照组FSH、LH、E2及AFC水平与术前比较,差异无统计学意义(P0.05),观察组患者FSH、LH水平较术前升高,E2及AFC水平较术前降低,且观察组患者FSH、LH水平高于对照组,E2及AFC水平低于对照组,差异均有统计学意义(P0.05);术后12周,观察组患者出现排卵异常、经量过少及经期延长的发生率均高于对照组(P0.05)。结论:缝合止血在腹腔镜下卵巢囊肿剥除术止血对患者卵巢功能的损伤作用小于电凝止血,术后卵巢功能恢复快,临床上应当优选缝合止血,降低对卵巢功能的影响。     

Effect of luteal metoclopramide-induced hyperprolactinemia on pituitary and luteal responsiveness to gonadotropin-releasing hormone

The pituitary and corpus luteum responses to acute gonadotropin-releasing hormone (GnRH) administration at the mid-luteal phase (LP) were studied in 24 infertile women. Patients were randomly divided into two groups. In one group (n = 12) metoclopramide (MCP, 10 mg orally 3 times daily) was administered from day 0 or 1 of the LP for 7 days. On day 7 or 8 of LP blood samples were taken every 15 min for 180 min; then 25 micrograms GnRH were acutely administered intravenously and blood samples taken at 185, 195, 210, 225, 240, 255, 270, 285 and 300 min. In the other 12 patients the same experimental design was performed on day 7 or 8 of an untreated LP. Plasma prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone and estradiol (E2) were assayed. The responsiveness of the different hormones to GnRH was evaluated as the integrated secretory area for 120 min after injection (sISA = stimulated integrated secretory area) and as the percentage increase (delta A) with respect to the area under basal conditions before GnRH administration (bISA = basal integrated secretory area). MCP-treated women showed higher basal PRL levels (p less than 0.01) and lower basal plasma concentrations and bISA (p less than 0.01) values of LH than controls. After GnRH a more marked response of LH secretion was observed in the treated group (p less than 0.01), so that the absolute values of sISA were superimposable in both groups. Basal and stimulated FSH secretion did not differ significantly in the study groups. Basal plasma and bISA values of progesterone were also decreased in MCP-treated subjects. After GnRH injection the absolute values of progesterone sISA were greater in controls (p less than 0.01), but delta A values were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Steroids and neuroendocrine function in anorexia nervosa

Anorexia nervosa is a primarily psychiatric syndrome of self-induced weight loss due to an intense fear of becoming obese. Numerous endocrine abnormalities occur in anorexia nervosa patients, and in many respects these alterations reflects the endocrinology of reduced energy intake. However, the basic mechanisms of those alterations are far from being understood. In an attempt to understand the disrupted mechanisms of the hypogonadotropic hypogonadism of the anorectic state, we studied 10 anorectic women in the acute phase of their illness; all met the DSM III criteria. On each patient, two tests were performed with either saline as control or infusion of the opioid antagonist naloxone, and both LH and FSH levels were measured. Four mg of naloxone as bolus was used, followed by a naloxone infusion of 2 mg/h for 4 h. Compared with the pattern of normal women, naloxone did not increase in the anorectic patients either LH or FSH levels nor pulsatility. This result suggests that endogenous opioid peptides are not implicated in the low gonadotropic situation of anorexia nervosa. An alternative explanation could be that the low estrogenic "milieu" of these patients could mask the opioid action. To test this second possibility, another group of 7 anorectic women after partial weight recovery were challenged with estrogen administration. Compared with the pattern of normal women volunteers, all the anorectic patients but one presented an abnormal response in both LH and FSH levels after estrogen administration. In fact, the negative feedback and the delayed positive feedback of LH after estrogen were absent in these patients. Interestingly enough, the only patient with near-normal LH response to estrogen was considered fully recovered by the Psychiatric Unit. Several alterations in the hypothalamic-pituitary-adrenal axis has been reported in anorexia nervosa. Seven anorectic patients and 7 aged-matched women were challenged by ACTH 1-24, 250 micrograms (i.v.) and the ratio of increments in adrenal steroid products to precursors monitored. ACTH-induced increments in cortisol with respect to increments in 17-OH-progesterone was similar in anorectics and controls. On the contrary, the ratio of increments of androstenedione with respect to increments in 17-OH-progesterone were greater in anorexia nervosa than controls. These results suggest that in anorexia nervosa the 11-beta-21-alpha-hydroxylase system is normal but a deficient 17-20 desmolase system is present. Finally, the altered pattern of GH secretion in anorexia was studied using GHRH (1 microgram/kg) as stimulus of pituitary GH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of 50 Hz magnetic field on sex hormones and body, uterine, and ovarian weights of adult female rats

The effects of extremely low-frequency (ELF) magnetic fields on sex hormones of adult female Spague-Dawley rats were investigated. Adult female rats were exposed to a 50 Hz sinusoidal magnetic field at approximately 25 microT (rms) for 18 weeks before they returned to their normal life with unexposed counterparts. Serum level of Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), progesterone, and estrogen were measured before, after, and during the exposure. Body and uterine weights were not affected by the field. A significant reduction in absolute and relative ovarian weights in exposed rats was observed when compared with sham-exposed controls (P < 0.05). The reduction in the levels of gonadotropins (FSH and LH) was significant after six weeks of exposure (P < 0.005). FSH levels were affected only on week 6 of exposure while LH remained affected during at 12 and 18 weeks (P < 0.05). Interestingly, no significant effects were found at 6 and 12 weeks after removing the field. The level of progesterone and estrogen was significantly decreased after 12 weeks of exposure (P < 0.05), while no other effects on progesterone level was observed during exposure or after removing the exposure. The level of estrogen was also significantly reduced at 12 weeks after removing the field (P < 0.05). These results suggest possible adverse effect on mammalian fertility and reproduction. The effects of ELF-MF on sex hormones were shown to be partly reversible.     

Pituitary regulation of preovulatory estrogen secretion in the rat

The factors stimulating estrogen secretion in the preovulatory phase and an attempt to explain the mechanism of termination of estrogen secretion are discussed. Female Wistar rats, hypophysectomized at 1 p.m. in proestrus, were injected with rat pituitary extracts. Ovarian venous blood was collected and the estrogen activity of the plasma was measured. The estrogen secretion was minimized within 3 hours after hypophysectomy. The rat pituitary extract caused an 11-fold increase of estrogen concentration in the ovarian venous blood within 1 hour. Either LH or FSH alone was able to restore the estrogen secretion: LH took 1 hour to reach maximal response, FSH 2 hours. In the 1-hour test, the minimal effective dose for LH appeared to be less than .25 mcg per rat, for FSH, 2.5 mcg per rat. The total ability of the two preparations to produce estrogen appeared to be the same. 10 I.U. of prolactin slightly stimulated estrogen secretion, but 20 mU of ACTH was quite negative. These results demonstrate the pituitary gonadotropin dependency of estrogen secretion from the ovary having ripened follicles. It also showed that the ovary, after completion of ovulatory surge of LH, abolished its reactivity to the pituitary extract containing sufficient amount of substances in promoting estrogen secretion. Either LH or FSH was able to terminate estrogen secretion even at minute doses as small as 10 mcg. This shows that both FSH and LH provide a dual effect on ovarian estrogen secretion at the preovulatory stage, promotion and suppression. Promotion is an acute and direct action of hormones on steroidogenesis and suppression probably a delayed and indirect action of ovulation-inducing hormone, the release of which initiates the differentiation of estrogen-forming cells towards ovulation unfavorable to estrogen synthesis.