LH and FSH responses to luteinizing-releasing hormone in normal,adult, human males

Time-response and dose-response relationships were established for the LH and FSH response to single intravenous bolus injections of synthetic LRH. Sixteen normal adult human males, ages 19–45 were studied, and 80 individual tests were performed using a broad range of LRH doses from 0–3000 μg. Serum gonadotropins were measured at frequent intervals ranging from ?30 to 180 min after LRH injection. The curves describing changes in blood LH and FSH with time were not superimposable at any dose level. The 50% decay time for the LH response showed a significant linear log-dose relationship to LRH.For LH, dose-response relationships existed for both, the peak LH release, and the total LH secretion (area under the time-response curve). No minimal or maximal effective doses were reached for LH within the dose range from 1 to 3000 μg LRH. The smallest dose (measured as peak LH concentration), that produced a response significantly different from saline injections, was 1.58 μg/subject; judged by total LH secretion (area under the time-response curve) the smallest dose producing a significant response was 2.39 μg/subject. No dose-response relationship existed for the peak FSH release. Judged by total FSH secretion (area under the time-response curve), the effects of LRH were dose related; the smallest effective dose was 20 μg LRH. As for LH, no maximal effective dose was reached within the dose range studied.The 95% confidence intervals for the peak responses to an intravenous bolus injection of 100 μg synthetic LRH were 400%–800% of the individual mean base line LH concentration, and 100%–200% of the individual mean base line FSH concentration. Serum testosterone did not change significantly in response to single bolus injections of LRH at any of the dose levels studied. The peak LH responses to any dose of LRH were positively correlated to the individual mean base line LH concentrations. No correlations were observed between the peak LH or FSH responses and age, race, marital status, body weight, or body surface area of the subjects.In a second series of studies, a 2-hr, constant infusion of synthetic LRH was administered at five different infusion rates (doses) to four normal adult human males for a total of 20 infusions. Serum LH and FSH responses were sustained at dose related levels characteristic of each individual during the entire LRH infusion period. In contrast to the lack of testosterone responses to bolus injections of LRH, serum testosterone rose significantly in response to all dose levels of LRH infusion. These are the most extensive pharmacologic studies of LRH-LH and LRH-FSH relations in man yet reported.     

Effects of morphine and naloxone on plasma levels of LH, FSH, prolactin and growth hormone in the immature male pig

The effects of acute i.v. administration of gonadotrophin-releasing hormone (GnRH; 0.1 micrograms/kg), morphine (3 mg/kg) and/or naloxone (0.5 mg/kg) on LH and FSH secretion was evaluated in young male pigs (approximately 6 weeks old) with venous brachiocephalic cannulae. The effects of morphine and/or naloxone treatments on prolactin and GH were also evaluated. The influence of morphine on hypophysial hormone secretion was also examined 2 days after castration. Animals treated with morphine and/or naloxone were compared with saline-injected control animals. Injection of GnRH induced 400 and 50% increases in LH and FSH respectively. Morphine and/or naloxone did not influence LH secretion in intact or castrated animals. Morphine suppressed (P less than 0.01) FSH levels 40-60 min after injection whereas naloxone had no effect. Castration eliminated morphine-induced suppression of FSH. Injection of morphine followed by naloxone resulted in acutely raised (P less than 0.05) FSH concentrations. Morphine induced a threefold increase (P less than 0.01) in prolactin within 30 min of injection and naloxone inhibited the effect of morphine. Levels of GH were increased (P less than 0.01) 20 min after morphine treatment and this increase was delayed when naloxone was given immediately after morphine. Naloxone alone did not affect prolactin or GH secretion. Castration caused increases in LH (P less than 0.05) and FSH (P less than 0.01), did not influence prolactin or GH, and reduced plasma testosterone to undetectable (less than 1.0 nmol/l) levels. These results suggest that in young male pigs the hypothalamic-hypophysial axis is responsive to GnRH and gonadal negative feedback.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous growth hormone secretion increases during puberty in normal girls and boys.

To test the hypothesis that GH secretion increases during puberty, we measured GH levels in samples obtained every 20 min for 24 h from 132 normal children and adolescents. In both girls and boys, GH levels increased during puberty. The increase in mean levels was earlier in girls than boys, was most evident at night, and was due to increased pulse amplitude rather than a change in pulse frequency. The mean nighttime GH level in girls with bone ages (BA) greater than 12 to 14 yr were significantly greater than the mean level in girls with BA less than 8 yr (7.3 +/- 3.0 vs. 3.4 +/- 1.7 micrograms/L; P less than 0.01) and were greatest at breast stage 3 (7.9 +/- 2.5 micrograms/L). GH pulse amplitude increased significantly before pubertal onset in girls and was significantly greater at BA greater than 12 to 14 yr than at BA of 8 yr or less (13.9 +/- 6.0 vs. 7.9 +/- 4.8 micrograms/L; P less than 0.01) and greatest at breast stage 3 (15.0 +/- 6.3 micrograms/L). The pubertal increase in GH secretion was delayed in boys compared to girls, with the lowest mean 24-h GH and mean nighttime GH values in boys with BA greater than 8 to 11 yr. The mean nighttime GH level at BA greater than 11 to 13 yr in boys was significantly greater than that in the boys with BA greater than 8 to 11 yr (5.8 +/- 2.9 vs. 3.5 +/- 2.1 micrograms/L; P less than 0.05) and was greatest at a testicular volume of more than 10 to 15 mL (6.5 +/- 2.0 micrograms/L). The mean nighttime GH pulse amplitude in boys was significantly greater at BA greater than 11 to 13 yr than at BA greater than 8 to 11 yr (13.9 +/- 5.7vs. 7.3 + 2.6 micrograms/L, P less than 0.05) and was greatest at a testicular volume greater than 20 mL (15.8 +/- 12.0 micrograms/L). The mean nighttime GH levels correlated inversely with body mass index in both sexes, although the correlation achieved statistical significance only for the girls, being stronger in breast stage 3 to 5 girls (r = -0.57 P = 0.0007; n = 32) than in stage 1 and 2 girls (r = -0.38; P = 0.03; n = 32). These observations in normal adolescents emphasize the importance of interpreting spontaneous GH levels in short children in relation to normative data appropriate for sex, body mass, and bone age or pubertal stage.     

Opioid modulation of FSH, growth hormone and prolactin secretion in the prepuberal gilt.

The role of endogenous opioid peptides (EOP) in modulating GH, prolactin (PRL) and FSH secretion was evaluated in prepuberal (P) gilts. In experiment I, P gilts received 1 (n = 2), 3 (n = 3) or 6 (n = 3) mg naloxone (NAL)/kg body weight i.v. Blood was collected every 15 min for 2 h prior to and 2 h after NAL and an additional 1 h after 100 micrograms gonadotrophin-releasing hormone (GnRH) i.v. In experiment II, P and mature (M) gilts were ovariectomized. Three weeks after ovariectomy, P and M gilts were injected twice a day for 10 days with either 0.85 mg progesterone (P4)/kg body weight or oil vehicle (V), resulting in the following groups: PP4 (n = 11), PV (n = 10), MP4 (n = 11) and MV (n = 10). All gilts received 1 mg NAL/kg body weight on the last day of treatment. Blood samples were collected every 15 min for 4 h before and 2 h after NAL and an additional 1 h after 100 micrograms GnRH i.v. In experiment III, six P and five M gilts were ovariectomized and surgically implanted with intracerebroventricular (i.c.v.) cannulae. Blood was collected every 15 min for 3 h before and 3 h after i.c.v. injection of 500 micrograms morphine in artificial cerebrospinal fluid (CSF) or 250 microliters CSF. In experiment I, all doses of NAL failed to alter PRL secretion, while NAL increased (P less than 0.05) GH secretion in three out of eight gilts. However, NAL suppressed (P less than 0.05) FSH concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence of different actions of testosterone, estradiol, FSH, and LH on the growth axis.

To study the possible role of sexual hormones, Testosterone (T), Estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) on the growth axis, we examined the correlations between the sex, growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP3), FSH, LH, T and E2, in growth retarded children ranging in age from 7 to 13 yr. All hormones were measured by Radioimmunoassay (RIA) in a pool of aliquots of samples obtained every 20 min over 12 h (overnight) in each child. Multivariate statistical analysis was performed. We have found: a) Thai only FSH concentrations were significantly higher in girls than in boys; b) A positive correlation between T-IGF-1; T-IGFBP3; FSH-LH; FSH-IGF-1; FSH-IGFBP3, LH-IGF-1, LH-IGFBP3 the sex-FSH; and the sex-IGFBP3 c) A high positive correlation between plasmatic E2 and IGF-1/IGFBP3 ratio (an index of free, active IGF-1). We concluded that the sex, FSH, LH, T and E2 influence the growth axis. The sex through IGFBP3; LH, FSH, and T through IGF1 and IGFBP3; E2 through the IGF-1/IGFBP3 ratio, an index of active IGF-1.     

Content of LH, FSH, and growth hormone in the pituitaries of pregnant and anestrous sheep.

The total content of LH, FSH, and growth hormone was measured in pituitaries from anestrous ewes and from ewes at known stages of pregnancy. LH content was lower in the pregnant ewes than in the anestrous group. Compared with the anestrous group, a significant drop in mean LH content was seen by days 40-50 of pregnancy (894 vs 350 mug, P less than 0.001), and it reached its lowest value by 120-135 days of pregnancy (43 mug, P less than 0.001). In sheep 148 days of pregnant, mean LH content was higher than in the latter group (155 mug). The correlation coefficient between the stage of gestation and the LH content was 0.63 (P less than 0.01). There was no significant change in mean FSH content in ewes up to 135 days pregnant (range 1196-1550 mug) compared with anestrous ewes (1023 mug). In the group 148 days pregnant (531 mug), a significant decrease was seen compared with ewes at other stages of pregnancy (P less than 0.05). Stage of gestation and FSH content were poorly correlated (r = 0.07). No significant differences in growth hormone content were seen in any of the groups. The results suggest that the progressive reduction in LH response to synthetic GnRH which has been reported for pregnant sheep may be due to selective inhibition of LH biosynthesis.     

Plasma and pituitary concentrations of LH, FSH and prolactin in aging mongolian gerbils

Samples of plasma and pituitary homogenates collected from female Mongolian gerbils (3–4, 11–13 and 20–25 month-old) at various stages of the estrous cycle were analyzed by radio-immunoassay for luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (Prl). Plasma and pituitary LH concentrations were similar in all three age groups. Plasma FSH concentrations tended to increase with age while plasma Prl concentrations remained unchanged. Pituitary concentrations of FSH and Prl were variable between the age groups depending upon the stage of the estrous cycle. The inability of older gerbils to produce young appears to result primarily from age-related changes occurring in the uterus rather than from alterations in the hypothalamic-hypophyseal complex.     

Luteinizing hormone (LH)-releasing hormone: effects of induction of LH, follicle-stimulating hormone, and prolactin cell differentiation

We investigated the influence of LHRH on the differentiation of gonadotrophs and lactotrophs in fetal pituitary glands transplanted beneath the renal capsules of adult hypophysectomized-orchidectomized hamsters (hosts). Hypophyses were removed from hamster fetuses at a gestational age of 14 days. Some of these were immediately fixed in Bouin's solution, and others were transplanted into the hosts. The hosts were injected sc twice daily with 1 microgram LHRH or vehicle for 16 days. Six hosts in each group were killed by decapitation 16 h after the last injection. Six 14-day-old normal male hamsters (age-matched to correspond to the age of the allografts at the time of the hosts' decapitation) also were decapitated. Sections of hypophyses in situ from fetal hamsters, from 14-day-old controls, and from allografts in each group were stained for LH, FSH, or PRL and with hematoxylin. No PRL-containing cells and very few LH or FSH cells (less than 0.025% of the adenohypophysial cell population) were observed in fetal pituitary glands. In allografts from the vehicle-treated hosts, 21.1% of adenohypophysial cells contained LH, but only 1.8% contained FSH. In allografts from LHRH-treated hosts, 28.0% and 22.9% of the adenohypophysial cells contained LH and FSH, respectively. Adenohypophyses that developed for the same length of time in situ had smaller percentages of adenohypophysial cells containing LH (23.8%) and FSH (15.5%) than the LHRH-treated group. LH-containing cells in allografts in the vehicle-treated hamsters, but not in the LHRH-treated animals, were reduced in size compared to those measured in situ. The number of lactotrophs in all allografted tissue was markedly reduced compared to that of lactotrophs in situ, and injection of LHRH into hamsters with allografts did not alter the percentage of adenohypophysial cells that were lactotrophs. These results suggest that in the hamster LHRH 1) plays an important role in stimulating the formation of immunoreactive FSH in the pituitary gland, 2) can increase the number of gonadotrophs that develop during the neonatal period, and 3) plays a role in controlling the size of gonadotrophs during development. The results also suggest that the development of lactotroph cell number requires close proximity to the hypothalamus and/or exposure to a neonatal environment. We found no evidence to support the view that LHRH, LH, or FSH stimulates immunoreactive lactotroph differentiation.     

Overnight follicle stimulating hormone (FSH) and luteinizing hormone (LH) excretion in normal males.

FSH and LH in acetone precipitates of timed overnight urine collections were measured by radioimmunoassay. FSH and LH urinary excretion extrapolated to 24 h was determined in 147 boys 3-16 years and 20 normal men. FSH and LH (2nd IRP-HMG) progressively increased with age from 1.8 +/- 1.1 (FSH) and 2.1 +/- 1.2 (LH) IU/24 h for the 3-4 year age group to 8.6 +/- 3.2 (FSH) and 18.8 +/- 9.0 (LH) IU/24 h for the 15-16 year age group. FSH and LH excretion increased progressively with stage of sexual development. The integration of several hours of FSH and LH secretion and the accuracy, simplicity and convenience of collecting a single urine sample are advantages of the timed overnight urine collection which should make this technique extremely useful in the evaluation of gonadotropin function.     

Growth hormone secretion patterns in relation to LH and testosterone secretion throughout normal male puberty

Pulsatile growth hormone secretion patterns were studied in relation to LH and testosterone release in 30 healthy prepubertal boys and 2 adult men. Plasma GH was measured every 10 min, plasma LH and testosterone every hour. Night-time GH secretion parameters were 2-3 times higher than daytime values. During daytime, mean GH level and the fraction of GH in pulses increased from Tanner stage G2 to G4 (p = 0.01); during night-time these parameters increased as well (p less than or equal to 0.1) and decreased from stage G5 to adulthood (p = 0.05). GH pulse number did not increase; the number of high-amplitude (greater than 8 micrograms/l pulses, however, increased from stage G2 to G4 (p = 0.05) during the day. Height velocity correlated with their number of high pulses during day and night (tau = 0.39, p less than 0.003). From stage G2 to G4 significant correlations were observed between nocturnal testosterone levels and GH secretion parameters (tau = 0.53-0.57), in contrast to nocturnal LH levels. It is concluded that during puberty 1. GH secretion increases as a result of an increased pulse amplitude; 2. there is no consistent correlation between GH and LH levels; 3. increasing nocturnal testosterone levels are correlated with the increasing GH secretion; therefore GnRH does not seem to influence GH secretion directly, but an indirect effect via testosterone is more conceivable, and 4. height velocity is correlated with the number of high GH pulses.     

Evidence of altered dopaminergic modulation of Prl, LH, FSH, GH and TSH secretion during chronic partial dopamine receptor blockade in normal women

In order to study the influence of chronic, partial dopaminergic blockade on pituitary secretion of Prl, TSH, GH, LH and FSH, 8 normally menstruating women were given metoclopramide (MTC, Primperan ) 7.5 mg daily for 4 weeks. Based on weekly measurements of progesterone, all cycles were ovulatory. Prior to and after 4 weeks of drug administration serial measurements of basal hormone levels as well as the acute alterations after 10 mg of MTC iv were assessed during the early follicular phase. Chronic MTC administration significantly increased serum Prl (P less than 0.02), reduced basal levels of LH (P less than 0.02), whereas basal serum concentrations of TSH, GH and FSH were not changed. Before chronic administration iv MTC evoked significant increments in serum Prl (P less than 0.001), TSH (P less than 0.001) and GH (P less than 0.005). The acute TSH increments were significantly (P less than 0.02) diminished after 4 weeks of treatment. The influence of chronic MTC administration on serum LH and TSH levels may be the result of a competitive effect of a stimulatory influence of the dopamine receptor blocker and an opposing inhibitory influence of an increased hypothalamic dopamine activity, evoked by the MTC induced hyperprolactinaemia. Our data favour that the latter mechanism is dominating in normal women, during chronic administration of a low dose of MTC.     

Effects of bromocriptine and naloxone on plasma levels of prolactin, LH and FSH during suckling in the female rat: responses to gonadotrophin releasing hormone

The roles of dopamine and the endogenous opiate peptides in the mediation of the inverse relationship between prolactin and gonadotrophin secretion during lactation were studied by comparing the effects of bromocriptine and naloxone on plasma levels of prolactin, LH and FSH during suckling in the female rat. The effects of exogenous gonadotrophin releasing hormone (GnRH) on the LH and FSH responses to bromocriptine and naloxone were also assessed. In control animals (saline), there was a marked fall in LH levels and a large increase in prolactin levels within 15 min of suckling. In response to GnRH (25 ng) there was a small progressive increase in LH levels reaching a maximum at 45 min. Both bromocriptine (500 micrograms) and naloxone (500 micrograms) markedly suppressed the suckling-induced prolactin surge when administered in two separate groups of animals. However, despite the bromocriptine-induced suppression of prolactin levels, there was no increase in LH levels which remained low throughout the suckling period. Naloxone (500 micrograms), however, induced a twofold increase in LH levels within 15 min suggesting that an enhanced opiate rather than dopaminergic activity may be responsible for the suppression of GnRH and hence gonadotrophin secretion during suckling. This is supported by the finding that whereas combined bromocriptine (500 micrograms) and GnRH (25 ng) treatment suppressed the suckling-induced prolactin rise and also induced only a small progressive increase in LH (similar to GnRH alone), combined naloxone (500 micrograms) and GnRH (25 ng) treatment induced a sharp sixfold increase in LH levels within 15 min while at the same time markedly suppressing prolactin levels. None of these drug treatments affected the levels of FSH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone secretion patterns in relation to LH and estradiol secretion throughout normal female puberty

Pulsatile growth hormone secretion patterns were studied in relation to luteinizing hormone and estradiol release in 33 healthy (pre)pubertal girls. Plasma GH was determined every 10 min, plasma LH and E2 every hour. Night-time GH release was always higher than daytime GH release. During daytime, all GH secretion parameters, except for the basal GH level, increased significantly from the prepubertal stage to stage B4 before (m-) the menarche (p = 0.05) and decreased thereafter (p = 0.05). During night-time, mean GH level and the fraction of GH in pulses also tended to increase from stage B1 to stage B4m-. The number of high pulses (greater than 8 micrograms/l) during day and night together tended to increase until stage B4m- and decreased after the menarche (p = 0.05). Height velocity did not correlate with the number of high pulses (Kendall tau = 0.14, p = 0.14). From stage B1 to B4m- high correlations were observed between E2 levels and GH secretion parameters, particularly during the day (tau = 0.59-0.71, p less than or equal to 0.01). The correlations between LH levels and GH secretion were high as well (tau = 0.50-0.81, p less than or equal to 0.01), but equal during day and night. It is concluded that during puberty 1. spontaneous GH release in girls increases 2-3 fold until the menarche and decreases thereafter, primarily as the result of an increasing and decreasing GH pulse amplitude; 2. diurnally increasing estradiol levels correlated with increasing GH secretion.