Suppressive actions of a gonadotropin-releasing hormone antagonist on luteinizing hormone, follicle-stimulating hormone, and prolactin release in estrogen-deficient postmenopausal women

We investigated time- and dose-dependent actions of a gonadotropin-releasing hormone antagonist, the "Nal-Glu" peptide [Ac-D2Nal1, 4CIDPhe2, D3Pal3, Arg5, DGlu6(AA), DAla10], in nine healthy estrogen-withdrawn postmenopausal women. Gonadotropin-releasing hormone antagonist was administered subcutaneously at doses of 10, 30, 100, and 300 micrograms/kg. Suppression of immunoactive luteinizing hormone concentrations was achieved with a 30 micrograms/kg dose of antagonist. Suppression of immunoactive follicle-stimulating hormone levels was less (40%) even at the highest antagonist dose (300 micrograms/kg). Bioactive luteinizing hormone concentrations also significantly decreased (greater than 60%) at the two antagonist doses tested (30 and 300 micrograms/kg). However, the lower antagonist dose showed an "escape" of bioactive luteinizing hormone values after 18 hours. No suppressive effects of the antagonist on prolactin secretion occurred at any dose tested. We conclude that this gonadotropin-releasing hormone antagonist can achieve effective, potent, and long-lasting suppression of pituitary secretion of biologically active luteinizing hormone at higher doses, but secretion of biologically active luteinizing hormone may "escape" at lower doses.     

The effect of follicle-stimulating hormone without additional luteinizing hormone on follicular stimulation and oocyte development in normal ovulatory women

Twelve normally menstruating women were stimulated with (1) human menopausal gonadotropins (hMG) containing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and (2) FSH only to induce growth of multiple follicles for oocyte retrieval. Maturation of the follicles and presumptively the oocytes was assessed by daily serum estradiol (E2) values, the response of the vaginal epithelium, and cervical mucus. The growth and number of follicles were measured by ultrasound daily. Human chorionic gonadotropin was administered as a surrogate LH surge. The hMG cycles were compared with the FSH-only cycles in relation to serum E2 and oocyte maturation, fertilization, transfer, and pregnancy rates. Five of eight cycles adequately stimulated with FSH only resulted in successful pregnancies. FSH without additional LH can initiate and maintain E2 function and allow oocyte maturation to proceed up to the terminal maturation, which is associated with the LH surge. The effect of LH may be to hasten follicular atresia in the developing cohort of follicles.     

A study of prolactin, follicle-stimulating hormone, and luteinizing hormone in puerperium: spontaneous variations and the effect of metergoline

In 80 normal puerperae, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), including human chorionic gonadotropin (hCG/LH), and prolactin (PRL) levels were evaluated 6 to 29 hours after vaginal delivery. In these puerperae, PRL levels were higher and FSH levels were lower than in menstruating women; hCG/LH levels were very high, due to persisting hCG levels. The values of the three hormones showed a log-normal distribution, and no relationship was found between the three hormones considered in pairs. Thirty-six puerperae chosen from the above 80 were followed during a 5-day period: 24 were not able to breast-feed their babies and were treated with metergoline, an antiserotoninergic agent able to prevent puerperal lactation, 8 or 12 mg/day; 12 additional puerperae, nursing their babies, were evaluated as controls. In lactating women PRL and FSH levels remained steady during the observation period, while hCG/LH levels progressively decreased. Metergoline lowered PRL levels, when employed at both dosages, and FSH levels only at the higher dosage, without affecting the decline of hCG/LH levels. Since dopaminergic drugs are known to lower serum LH levels and not to affect or to increase FSH levels, our data indicate that metergoline might act through a mechanism of action different from dopaminergic drugs.     

A marathon: the immediate effect on female runners' luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, and cortisol levels

This study was designed to measure the changes that occur in luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, testosterone, and cortisol levels in women at the immediate conclusion of a marathon and to compare the results with those in women on the United States Women's Water Polo Team at the conclusion of a strenuous practice session. Thirty-one women runners were included in this study, and each woman served as her own control. Thirteen women were studied from the United States Women's Water Polo Team. In the postmarathon group, cortisol levels showed a mean increase of 211% (p = less than 0.005), FSH levels were unchanged; LH levels, contrary to other published reports, were reduced by 36% (p = less than 0.005); and prolactin levels showed a mean increase of 327% (p = less than 0.005). These results were analyzed in the age groups 20 to 30, 30 to 40, and 41 +. All age groups had similar changes. In members of the United States Women's Water Polo Team, there were no significant changes in cortisol, FSH, LH, or testosterone levels. Prolactin levels showed an average increase of 70% (p = less than 0.002). These data indicate that acute exercise by running a marathon does alter the immediate hormonal profile. The data also indicate that acute exercise in an aquatic program results in a different response.     

The effect of varying prolactin levels on pituitary luteinizing hormone and follicle-stimulating hormone response to gonadotropin-releasing hormone.

Seventy-one women with menstrual irregularities were investigated by measurement of basal plasma estradiol, prolactin, and gonadotropin levels. They were each given an intravenous injection of 100 microgram of gonadotropin-releasing hormone (GnRH), and both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured for two hours. The women were divided into three groups on the basis of the prolactin levels: "normal," "mild elevation," and "severe elevation." For each prolactin group there was no difference in age or estradiol or basal LH and FSH levels. The pituitary response to the GnRH injection was also similar for the three groups. These data suggest that elevated prolactin levels do not interfere with pituitary gonadotropin cell function.     

Immunohistochemical localization of follicle-stimulating hormone, luteinizing hormone, growth hormone, adrenocorticotrophic hormone and prolactin in the human placenta

The sites of localization of luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and prolactin (PRL) within placental tissues have been studied by an immunoperoxidase technique. The syncytiotrophoblast is the sole significant site of localization of LH, FSH, GH and ACTH; PRL is found both in syncytiotrophoblast and in decidual cells. It is highly probable that the sites of localization of these peptide hormones represents their sites of synthesis in the placenta and thus that the syncytiotrophoblast is the sole site of synthesis of LH, FSH, LH and ACTH. PRL appears to be synthesized both in syncytiotrophoblast and decidua, but the latter is probably not the major site of synthesis of this hormone. Whether these placental peptide hormones have any physiological role to play during pregnancy or whether the placental capacity to synthesize such hormones is an atavistic phenomenon of no functional importance is currently a moot point.     

Recombinant follicle-stimulating hormone stimulates ovarian androgen synthesis in down-regulated ovulatory women

In order to study androgen secretion during controlled ovarian hyperstimulation for in-vitro fertilization-embryo transfer ,an open randomized study comparing the response to recombinant or urinary follicle-stimulating hormone (FSH) in down-regulated cycles was performed. During FSH administration significant increases in testosterone ,androstenedione and dehydroepiandrosterone sulfate (DHEAS) levels were observed. During the same period a slight decrease in luteinizing hormone (LH) levels was seen. At all times during the stimulation period a significant correlation between estradiol and testosterone or androstenedione levels was observed. We conclude that FSH ,through granulosa derived paracrine factors ,initiates thecal androgen synthesis and secretion.     

Effect of suckling on serum prolactin, luteinizing hormone, follicle-stimulating hormone, and estradiol during prolonged lactation

Eight nursing subjects had serum prolactin (PRL), luteinizing hormone, follicle-stimulating hormone, and estradiol levels studied during the first six months postpartum. Each subject had serum samples obtained just before the initiation of suckling and during the next 120 minutes. Baseline PRL levels were high at ten days postpartum (90.1 ng/mL), then slowly declined but remained elevated at 180 days postpartum (44.3 ng/mL), with the stimulus of suckling being able to double the baseline PRL value throughout the study period. Mean estradiol levels were low at ten days postpartum (7.2 pg/mL), then gradually rose to a mean level of 47.3 pg/mL at 180 days postpartum; however, in four subjects who were amenorrheic during the study period, the mean estradiol levels remained low (4.25 pg/mL), while baseline PRL levels remained high (63.6 ng/mL).     

Correlation between follicle-stimulating hormone, luteinizing hormone, prolactin, and testosterone with sperm cell concentration and motility

Follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone were measured by radioimmunoassay in blood and seminal plasma of normo-spermic and oligospermic men. These parameters were correlated with sperm cell concentration as well as sperm motility. Average motility in the oligospermic group was significantly decreased as compared with the normospermic group (P less than .001). A significant reciprocal correlation was demonstrated between blood LH concentrations and sperm cell concentrations (P less than .05) as well as sperm motility (P less than .02). In contrast, a significant positive correlation was demonstrated between seminal LH concentrations and sperm cell count and motility (P less than .001). Seminal FSH and testosterone concentrations were positively correlated with sperm output but not sperm motility (P less than .05). The increased concentrations of LH in circulation accompanying idiopathic oligospermia suggests that LH secretion may be linked to the factors regulating spermatogenesis. The significant correlation between seminal testosterone and sperm concentration demonstrated in this study offers further support to this hypothesis. The significance of the correlation between the levels of LH and FSH in seminal plasma and sperm cell concentration and sperm motility is unknown.     

Depressed follicle-stimulating hormone, luteinizing hormone, and prolactin responses to the luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and metoclopramide test in endurance runners in the hard-training season

The responses of serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to luteinizing hormone-releasing hormone (LH-RH) and the responses of prolactin (PRL) to thyrotropin-releasing hormone (TRH) and metoclopramide (MC) were measured in the late luteal phase of the cycle in 12 endurance runners and 11 control women and in 12 joggers and 7 control women. LH-RH (100 micrograms) and TRH (200 micrograms) were injected intravenously at the beginning of the test, and MC (10 mg) was injected 60 minutes later. Blood samples were obtained before and 20, 60, 80, and 120 minutes after the beginning of the test. Runners had significantly lower serum concentrations of estradiol and progesterone than control subjects, whereas the concentrations of FSH, LH, and PRL were similar at the beginning of the study. Compared with their controls, the runners had significantly lower FSH (P less than 0.05) and LH responses at 20 minutes (P less than 0.05) and lower LH responses at 80 minutes (P less than 0.01) to LH-RH and lower PRL responses to MC 20 minutes after MC injection (P less than 0.05). Joggers and their control subjects had similar LH, FSH, and PRL responses to these pharmacologic stimuli. It is concluded that decreased ovarian activity explains, at least partly, the lowered responses of FSH and LH to LH-RH and the lowered response of PRL to MC in endurance runners.     

Daily follicle-stimulating hormone, luteinizing hormone, estradiol, and progesterone in ten women harboring uterine leiomyomas

Serum follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were assessed every day in ten women harboring uterine leiomyomas during a complete menstrual cycle. Total area under the curve was individually calculated for E2 and P. The results obtained in this group were then compared with those obtained in a control population. No statistical difference was found. We concluded that patients harboring uterine leiomyomas had, in this study, a normal menstrual cycle. The role of estrogens in the physiopathology of uterine leiomyoma was not related to abnormally high levels of serum E2 or abnormally low levels of P.     

Recombinant follicle-stimulating hormone stimulates ovarian androgen synthesis in down-regulated ovulatory women.

In order to study androgen secretion during controlled ovarian hyperstimulation for in-vitro fertilization-embryo transfer, an open randomized study comparing the response to recombinant or urinary follicle-stimulating hormone (FSH) in down-regulated cycles was performed. During FSH administration significant increases in testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS) levels were observed. During the same period a slight decrease in luteinizing hormone (LH) levels was seen. At all times during the stimulation period a significant correlation between estradiol and testosterone or androstenedione levels was observed. We conclude that FSH, through granulosa derived paracrine factors, initiates thecal androgen synthesis and secretion.