Alteration in the normal pattern of serum testosterone and 5α-androstane-3α,17β-diol in the immature male rat following chronic treatment with luteinizing hormone releasing hormone or luteinizing hormone

A major component of sexual maturation in the male rat is a progressive decline in serum concentrations of 5α-androstane-3α,17β-diol (3α-diol) and a concomitant increase in testicular testosterone biosynthesis and secretion. Chronic administration of synthetic luteinizing hormone releasing hormone (LHRH) or luteinizing hormone (LH)/human chorionic gonadotropin (hCG) to immature male rats has been shown to result in a delay in sexual maturation as evidenced by decreased sex accessory gland weights and altered testicular testosterone production. We have examined the postulate that such treatments may either reverse or retard the normal developmental pattern of serum testosterone and 3α-diol concentrations. Chronic $\text{in vivo}$ treatment of 28 day old immature male rats for 2 weeks with daily injections of either 0.5 μg of LHRH, 1.0 μg of LHRH, or 30 μg of LH was found to result in significant reductions in weights of the seminal vesicles and ventral prostate glands and diminutions in serum testosterone concentrations. Serum content of 3α-diol was either unchanged or slightly elevated in the LHRH treated animals and increased significantly in the LH treated animals. These data suggest that either a reversal of or retardation in the normal developmental pattern of serum testosterone and 3α-diol content has been achieved in the immature male rat by chronic LHRH or LH treatment.     

Changes in circulating levels of immunoreactive follicle stimulating hormone, luteinizing hormone, and testosterone during sexual development in the rhesus monkey, Macaca mulatta

Basal serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) and the responsiveness of these hormones to a challenge dose of luteinizing hormone releasing hormone (LHRH), were determined in juvenile, pubertal, and adult rhesus monkeys. The monkey gonadotrophins were analyzed using RIA reagents supplied by the World Health Organization (WHO) Special Programme of Human Reproduction. The FSH levels which were near the assay sensitivity in immature monkeys (2.4 +/- 0.8 ng/ml) showed a discernible increase in pubertal animals (6.4 +/- 1.8 ng/ml). Compared to other two age groups, the serum FSH concentration was markedly higher (16.1 +/- 1.8 ng/ml) in adults. Serum LH levels were below the detectable limits of the assay in juvenile monkeys but rose to 16.2 +/- 3.1 ng/ml in pubertal animals. When compared to pubertal animals, a two-fold increase in LH levels paralleled changes in serum LH during the three developmental stages. Response of serum gonadotrophins and T levels to a challenge dose of LHRH (2.5 micrograms; i.v.) was variable in the different age groups. The present data suggest: an asynchronous rise of FSH and LH during the pubertal period and a temporal correlation between the testicular size and FSH concentrations; the challenge dose of LHRH, which induces a significant rise in serum LH and T levels, fails to elicit an FSH response in all the three age groups; and the pubertal as compared to adult monkeys release significantly larger quantities of LH in response to exogenous LHRH.     

Effects of ethanol on rat hypothalamic luteinizing hormone releasing hormone. A study utilizing radioimmunoassay

To further understand the mechanism of action by which ethanol (ETOH) decreases plasma luteinizing hormone (LH) levels, the effects of multiple i.p. injections of EOH (1.0--1.5 g/kg) or saline on hypothalamic luteinizing hormone releasing hormone (LHRH) and plasma LH concentrations were evaluated in intact and castrate male rats. After injections, animals were decapitated, brains rapidly removed, and blocks containing the hypothalamus [with median eminence (ME)] were isolated. Hypothalami were subjected to acetic acid extraction and LHRH content quantitated via radioimmunoassay (RIA). Hypothalamic LHRH was found to be inversely correlated with plasma LH. In response to castration, both saline and ETOH-treated rats showed a decrease in hypothalamic LHRH content with a concomitant increase in plasma LH; however, the ETOH-treated animals retained significantly greater concentrations of LHRH and showed significantly lower plasma LH levels when compared to saline-treated controls. Likewise, ETOH-treated intact animals showed significant increases in LHRH content, with LH levels remaining significantly lower than the saline-treated intact controls. Thus, these data from both intact and castrate rats provide evidence to support the hypothesis that alcohol-induced decreases in LH levels are due to a diminished release rate of hypothalamic LHRH.     

Contraception with LHRH agonists, a new physiological approach

The paradoxical antifertility effects of luteinizing hormone releasing hormone (LHRH) agonists in experimental male and female animals have been reported. Treatment with LHRH induces luteolysis and inhibits ovulation in normal women; in men, the same treatment decreases testicular steroidogenesis. This paper examines the mechanisms responsible for the paradoxical antifertility effects of LHRH agonists. A series of experiments was conducted in rats to determine the following: 1) the effect of lower and more physiological doses of the LHRH agonist on testicular gonadotropin receptors, 2) the time course of the effect of daily administration of 1 mcg of LHRH agonist on testicular and plasma concentration of steroid intermediates, 3) cellular changes occurring in the testis during longterm administration of the agonist, and 4) characteristics of LHRH receptors in the testis. The results show that LHRH agonists: 1) produce an inhibiting effect on testicular prolactin receptor concentrations, 2) can cause a dramatic fall in testicular androstenedione and testosterone concentration following treatment, 3) induce degenerative cellular changes in rat testis during longterm administration, and 4) may play a role in the physiological control of gonadal functions by a locally produced LHRH-like molecule. Similar experiments on the ovarian functions in female rats show that relatively low doses of LHRH agonist leads to marked loss of ovarian LH (luteinizing hormone) receptor accompanied by a decreased plasma progesterone concentration and uterine weight. The presence of specific ovarian LHRH receptors raises the possibility that LHRH secreted locally could be involved in the control of ovarian activity. In 6 normal men, a single intranasal administration of a potent LHRH agonist clearly showed inhibition of testicular steroidogenesis while studies on the luteolytic and antiovulatory activity in normal women demonstrated a luteolytic action of LHRH and its agonists. Progesterone secretion from the corpus luteum is important for the implantation and the maintenance of early pregnancy. The intranasal route of administration of LHRH agonists offers the advantage of easy, routine application by the general population.     

The response of the anterior pituitary and testes to synthetic luteinizing hormone-releasing hormone (LHRH) and the effect of castration on pituitary responsiveness in the maturing chicken fed aflatoxin

The responsiveness of the anterior pituitary to exogenous luteinizing hormone-releasing hormone (LHRH; 20 micrograms/kg body weight) and the subsequent stimulation of testosterone secretion by the testes was studied after administration of dietary aflatoxin (10 ppm) to 9-wk-old male chickens. In both control and aflatoxin-treated males, there were significant (p less than 0.05) increases in plasma luteinizing hormone (LH) concentrations following LHRH administration, which peaked at 5 min post injection and declined thereafter. Plasma testosterone levels increased soon after the LHRH injection in control males, secondary to elevated LH levels in the peripheral circulation, and continued to increase throughout the experimental period. In contrast, this LH-induced elevation in plasma testosterone was delayed in aflatoxin-treated males, with no substantial increase until 20 min post-LHRH injection. In a subsequent experiment, castration of aflatoxin-fed males resulted in an altered response to exogenous LHRH, as compared to their intact counterparts. Based on these data, it appeared that while the LH-secretory capacity of the anterior pituitary was not diminished in birds receiving aflatoxin, the testicular response to exogenous LHRH was altered during aflatoxicosis. Additionally, the effect of castration on plasma LH profiles after LHRH administration provides preliminary evidence for extra-testicular effects of dietary aflatoxin on reproduction in the avian male.     

Effects of aging on pituitary and testicular luteinizing hormone-releasing hormone receptors in the rat

Aging exerts profound influences on the function of the hypothalamic-pituitary-testicular-axis. This work has been performed in order to verify whether, in male rats, the decreased secretion of LH and testosterone (T) occurring in old animals is reflected by modifications of luteinizing hormone-releasing hormone (LHRH) receptors at the level of the anterior pituitary and of the testes. To this purpose, the affinity constant (Ka) and the maximal binding capacity (Bmax) for the LHRH analog [D-Ser(tBu)6]des-Gly10-LHRH-N-ethylamide were evaluated, by means of a receptor binding assay, in membrane preparations derived from the anterior pituitary and testicular Leydig cells of male rats of 3 and 19 months of age. Serum levels of LH and T were measured by specific RIAs. The results obtained show that, in aged male rats, the concentration of pituitary LHRH receptors is significantly lower than that found in young animals. On the other hand, the concentration of LHRH binding sites is significantly increased on the membranes of Leydig cells of old rats. In no instance the Ka for the LHRH analog is significantly affected. Serum levels of LH and T are significantly lower in old than in young male rats. In conclusion, these results suggest that the reduced secretion of LH in old male rats may be linked, at least partially, to a decrease of the number of pituitary LHRH receptors. The impaired production of testosterone occurring in aged rats is accompanied by a significant increase of the number of testicular LHRH receptors, indicating that also the intratesticular mechanisms controlling testosterone release undergo significant alterations with aging.     

Feedback regulation of gonadotropic hormone secretion in neonatal pigs

The effect of castration and of administration of charcoal-treated porcine follicular fluid (pFF) containing inhibin-like activity on plasma concentration of gonadotropic hormones was studied in neonatal pigs. Plasma follicle-stimulating hormone (FSH) concentration averaged 25.1 +/- 1.5 ng/ml (mean +/- SEM) in 1-wk-old females and gradually declined to 20.2 +/- 0.7 ng/ml 6 wk later. Ovariectomy did not significantly influence plasma FSH concentration. In males, concentration averaged 8.0 +/- 0.7 ng/ml before castration but rose significantly within 2 days after castration. Injection of luteinizing hormone-releasing hormone (LHRH) did not influence plasma FSH concentrations in intact males, but did in females and in 7-wk-old males castrated at 1 wk. Plasma luteinizing hormone (LH) concentrations in 1-wk-old females (2.2 +/- 0.4 ng/ml) gradually declined and were not influenced by castration. Concentrations of plasma LH in 1-wk-old male piglets (2.8 +/- 0.7 ng/ml) were not significantly influenced by castration within 2 days but were significantly higher 6 wk later. LHRH induced a significant rise in plasma LH concentrations in all animals. Injection of pFF resulted in a decline of plasma FSH concentrations in intact and castrated males and in intact females, but did not influence plasma LH concentrations. These data demonstrate a sex-specific difference in the control of plasma FSH, but not in plasma LH concentration in the neonatal pig. Plasma FSH concentrations, but not plasma LH concentrations, are suppressed by testicular hormones in 1-wk-old piglets. Plasma FSH concentrations can be suppressed in both neonatal male and female pigs by injections of pFF.     

Neuroendocrine control of gonadotropin secretion

Luteinizing hormone releasing hormone (LHRH), a hypothalmic peptide that is concentrated in granules of neurons, has the capacity to release gonadotropins (luteinizing hormone (LH) and follicle stimulating hormone) from the pituitary gland. LHRH has been found in hypophysial portal blood of rats, monkeys, and rabbits. Antibodies to LHRH depress plasma LH concentrations in castrated animals and evoke testicular atrophy, but passive immunization against LHRH does not block the LH surge induced by estrogen in monkeys. Estrogens, progestin, prolactin, and dopamine have marked effects on LH secretion, yet an association between these effects and altered hypophysial portal blood concentrations of LHRH is not established. In view of the paucity of evidence demonstrating such a cause and effect relationship, two alternative proposals have become tenable. One, hormones and neurotransmitters may not alter the levels of portal blood LHRH, but rather alter the frequency of pulsatile LHRH secretion. Two, hormones, such as estrogens, progesterone, and prolactin, may alter the responsiveness of the gonadotropin-secreting cells to LHRH by affecting the secretion of dopamine.     

Effect of bombesin on basal and stimulated secretion of some pituitary hormones in humans

The effect of bombesin (5 ng/kg/min X 2.5 h) on basal pituitary secretion as well as on the response to thyrotropin releasing hormone (TRH; 200 micrograms) plus luteinizing hormone releasing hormone (LHRH; 100 micrograms) was studied in healthy male volunteers. The peptide did not change the basal level of growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). On the contrary, the pituitary response to releasing hormones was modified by bombesin administration. When compared with control (saline) values, prolactin and TSH levels after TRH were lower during bombesin infusion, whereas LH and FSH levels after LHRH were higher. Thus bombesin affects in man, as in experimental animals, the secretion of some pituitary hormones.     

Nutritional influences on sexual maturation in the rat

The effect of altered nutrition on sexual maturation may depend in part on the nature and timing of the dietary change. The data are conflicting as to whether rats undernourished before weaning but normally fed after weaning have delayed puberty, but such undernourished rats clearly weigh less at vaginal opening than do normally fed animals. Altered nutrition after weaning can change the timing of puberty, and in such cases the body weight at puberty of the animals given the modified diet is frequently abnormal. The factors regulating the age and weight at puberty of rats fed altered diets seem to include the degree of underfeeding, as reflected in the growth rate, and the composition of the diet. Undernourished immature male rats have low serum testosterone secondary to gonadotropin deficiency. Basal luteinizing hormone (LH) in these animals is either low or "inappropriately normal" relative to their hypoandrogenic state (low serum testosterone and sexual accessory gland weights), and serum LH increases after luteinizing hormone-releasing hormone (LHRH) or castration are normal or minimally reduced. Serum follicle-stimulating hormone (FSH) in undernourished rats is subnormal basally and after administration of LHRH, but not after castration, which suggests that the low basal serum FSH is due to inhibition of FSH output by a testicular factor. Spermatogenesis may be unaltered by dietary changes severe enough to cause hypoandrogenism, although very severe under-nutrition will impair sperm production.     

Stress induced changes in testis function

The mechanism through which chronic stress inhibits the hypothalamic-pituitary-testicular axis has been investigated. Chronic restraint stress decreases testosterone secretion, an effect that is associated with a decrease in plasma gonadotropin levels. In chronically stressed rats there was a decrease in hypothalamic luteinizing hormone-releasing hormone (LHRH) content and the response on plasma gonadotropins to LHRH administration was enhanced. Thus the inhibitory effect of chronic stress on plasma LH and FSH levels seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a modification in LHRH secretion. It has been suggested that beta-endorphin might interfere with hypothalamic LHRH secretion during stress. Chronic immobilization did not modify hypothalamic beta-endorphin, while an increase in pituitary beta-endorphin secretion was observed. Since we cannot exclude that changes in beta-endorphin secreted by the pituitary or other opioids may play some role in the stress-induced decrease in LHRH secretion, the effect of naltrexone administration on plasma gonadotropin was studied in chronically stressed rats. Naltrexone treatment did not modify the decrease in plasma concentrations of LH or FSH. These findings suggest that the inhibitory effect of restraint on the testicular axis is exerted at hypothalamic level by some mechanism other than opioids.     

Delay in the age of balano-preputial skinfold cleavage and alterations in serum profiles of testosterone, 5 alpha-androstane-3 alpha,17 beta-diol, and gonadotropins in adult rats treated during puberty with luteinizing hormone releasing hormone

Previous work has shown that chronic treatment of intact, immature male rats with luteinizing hormone releasing hormone (LHRH) decreases sex accessory gland weights and results in retardation of the normal developmental increase in the ratio of serum testosterone (T)/5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Diol) via an apparent enhancement of testicular 5 alpha-reductase or 3 alpha-hydroxysteroid oxidoreductase activities. In the present work, androgen dependent balano-preputial skinfold cleavage was significantly delayed by approximately one week in intact, immature male rats which were treated daily for two weeks with either 1.0 micrograms, 2.5 micrograms or 5.0 micrograms of LHRH during a discrete phase of pubertal development (28-41 days of age). In intact, adult (62 day old) animals which received LHRH treatments during pubertal development, serum T concentrations and sex accessory gland weights were reduced compared to control animal values. Serum 3 alpha-Diol content in the adult rats was either unaltered or increased significantly depending on the LHRH dosage employed during sexual development. Serum luteinizing hormone concentrations were not different between control and LHRH-pretreated adult rats whereas the highest dosage of LHRH employed (5.0 micrograms) during puberty resulted in a significant elevation of adult serum follicle stimulating hormone levels. It is suggested that chronic LHRH treatment of the male rat during puberty results in a perturbation in testicular androgen biosynthetic activities and an impairment of pituitary-testicular hormone feedback mechanisms which persist at least through early adulthood.     

Porphyrin metabolism in the harderian glands of Syrian hamsters: in vivo regulation by testicular hormones, lighting conditions, pineal gland, and pituitary hormones.

The porphyrin concentration in the harderian glands of male hamsters subjected to several endocrine manipulations was studied. Prolonged bilateral gonadectomy resulted in a marked increase in harderian porphyrin concentration. This change was not prevented by either pinealectomy or by constant white light exposure. Castrated hamsters exposed to constant red light showed higher porphyrin concentrations than castrated hamsters kept under white light. Among several hormones studied, serum luteinizing hormone and thyroid-stimulating hormone levels were unexpectedly higher in the constant red light exposed group than in the other groups. In order to test whether luteinizing hormone was involved in the postcastrational rise in harderian porphyrins, we administered a potent luteinizing hormone-releasing hormone (LHRH) agonist. The chronic administration of the LHRH agonist resulted in a decrease in serum luteinizing hormone (because it desensitized the LHRH receptors on the gonadotropes) and, consequently, in serum testosterone levels. However, no rise in harderian porphyrin was observed. It is concluded that the absence of testicular hormones might not be the triggering factor involved in harderian porphyrogenesis.     

Alterations in hypothalamic content of luteinizing hormone-releasing hormone associated with pineal-mediated testicular regression in the golden hamster

The adult male golden hamster will undergo testicular regression when exposed to a short photoperiod, blinding, or late afternoon injections of melatonin. The present study was conducted to compare the effects of all three treatments on serum gonadotropin levels and testicular weights, and to evaluate the effects of these treatments on hypothalamic content of both immunoreactive and bioactive luteinizing hormone-releasing hormone (LHRH) levels. Hamsters were blinded (BL), exposed to a short photoperiod (SP), or received daily injections of melatonin (MEL) for 15 wk. Each treatment (BL, SP, MEL) induced a temporally similar decline in serum luteinizing hormone (LH), serum follicle-stimulating hormone (FSH), and testicular weight. Spontaneous recrudescence occurred earliest in the MEL group, with serum gonadotropins and testicular weight returning to normal by 15 wk. The SP group exhibited recovery of serum gonadotropins but not testicular weight by 15 wk. The BL group demonstrated partial recovery of serum FSH levels by 15 wk, with no recovery in either serum LH or testicular weight. Each treatment group demonstrated increased hypothalamic content of immunoreactive LHRH which was temporally correlated with the decreases of serum gonadotropins. Additionally, the MEL and SP groups demonstrated decreased immunoreactive LHRH levels during spontaneous recrudescence. Extracts of hypothalami from all treatment groups were bioactive on control hamster pituitary cells. These results indicate that there are temporal differences among the three common treatments and that these differences are manifested in serum gonadotropins, testicular weight and hypothalamic LHRH. Hypothalamic LHRH levels determined by radioimmunoassay and bioassay show periods of increase and decrease which coincide with periods of altered serum gonadotropin levels in all groups.     

Effects of luteinizing hormone releasing hormone on gonadotrophins in the hamster

The changes in serum gonadotrophins in male hamsters following one injection of 15 μg luteinizing hormone releasing hormone (LHRH) (Group A) were compared with those following the last injection of LHRH in animals receiving an injection approximately every 12 hr for 4 days (Group B) or 12 days (Group C). Peak follicle stimulating hormone (FSH) levels (ng/ml) were 1776±218 (Group A), 2904±346 (Group B), and 4336±449 (Group C). Peak luteinizing hormone (LH) values (ng/ml) were 1352±80 (Group A), 410±12 (Group B), and 498±53 (Group C). Serum FSH:LH ratios, calculated from the concentrations measured 16 hr after the last LHRH injections, were higher in Groups B and C than in Group A. Similar injections of LHRH (100 ng or 15 μg/injection) for 6 days elevated the serum FSH:LH ratio in intact males. Five such LHRH injections (100 ng/injection) blunted the rise in serum LH in orchidectomized hamsters. Direct effects of LHRH on gonadotrophin secretory dynamics or altered brain-pituitary-testicular interactions may alter the ratio of FSH to LH in the hamster.     

Pituitary and ovarian responses to luteinizing hormone releasing hormone in a rat with polycystic ovaries

Female rats injected with a single dose of 2 mg estradiol valerate (EV) develop anovulatory acyclicity characterized by persistent vaginal cornification and the formation of multiple large cystic follicles on the ovaries. In order to determine if these effects of EV are accompanied by changes in ovarian and/or pituitary function, the following studies were conducted. Ovarian androgen production was determined by the measurement at 4, 5 and 6 weeks after EV treatment of circulating dehydroepiandrosterone, androstenedione and testosterone. The capacity of the polycystic ovary to ovulate in response to luteinizing hormone releasing hormone (LHRH) stimulus was assessed. Ovarian histology was examined at the termination of the study (9 weeks after EV treatment). Pituitary function was assessed 9 weeks after the EV treatment by examining the acute changes in plasma luteinizing hormone (LH) concentration in response to a double pulse of LHRH. Plasma concentrations of the androgens were unchanged over the 3-week sampling period and were similar to those found in sesame-oil-treated normal cycling control rats. The ovaries from EV-treated animals were smaller than those of controls and the cystic follicles exhibited marked thecal hypertrophy and attenuation of the granulosa cell layer. The basal plasma LH concentration at 9 weeks after EV treatment were significantly lower than in proestrus controls and plasma concentrations of LH elicited by LHRH pulses was significantly lower than in controls. The relative increase in plasma LH following the LHRH stimulus was, however, greater in the EV-treated animals than in controls. In spite of the diminished LH surge elicited in response to LHRH, the EV-treated animals ovulated as indicated by the presence of fresh corpora lutea on the ovaries. These results indicate that androgens are not responsible for the polycystic ovarian condition in this system and that the polycystic ovary is capable of ovulatory function when appropriately stimulated.     

Seasonal changes in thyroid-gonadal interactions in the edible dormouse,Glis glis

Summary This study was conducted to determine changes in thyroid-gonadal interaction in the edible dormouse during the phase of the annual cycle that corresponds to the end of the breeding season (from June to September). We evaluated intra-hypothalamic luteinizing hormone-releasing hormone (LHRH) content, and plasma concentrations of luteinizing hormone (LH), testosterone, thyroid-stimulating hormone (TSH) and thyroxine (T4) in three groups of dormice: (1) controls; (2) dormice receiving sufficient T4 supplementation to maintain June levels in control animals until September, thus counteracting the seasonal reduction of T4 that normally begins in July; and (3) thyroidectomized dormice. The effect of thyroidectomy was only detectable in June, when plasma T4 concentration in the control group was maximal, and consisted of a significant decrease in plasma testosterone levels. This provides strong support for the hypothesis that thyroid function positively influences gonadal function during the breeding season. The T4 supplementation resulted in a decrease in hypothalamic LHRH concentration, suggesting that an increased LHRH release led to the observed stimulated hypophyseal secretion of LH in June and September and the increased circulating testosterone levels in September. There was no detectable effect in July and August. These results show that thyroid axis activation of the hypothalamic-pituitary-gonadal system is only possible during certain phases of the annual cycle, particularly evidenced here during the breeding season. They also reinforce our conclusions drawn from the thyroidectomy results. Conversely, the summer testicular regression which normally occurs after the breeding season is no longer controlled by plasma T4 levels. Even though the sensitivity of the gonadal axis to the thyroid axis appears to reappear at the end of the summer, results of previous studies indicate that this resumption is only temporary.Abbreviations LH luteinizing hormone - LHRH luteinizing hormone-releasing hormone - RIA radioimmunoassay - T4 thyroxine - TSH thyroid-stimulating hormone     

Leptin acts centrally to induce the prepubertal secretion of luteinizing hormone in the female rat

Recent data generated from adult male and female rats indicates that leptin is capable of stimulating luteinizing hormone (LH) secretion via a hypothalamic action. Consequently, we hypothesized that this peptide may similarly play a role in controlling LH secretion during late juvenile and peripubertal development; hence, contributing to hypothalamic-pituitary function during sexual maturation. Therefore, this study was conducted to determine if leptin is capable of stimulating LH release during this critical time of development and, if so, to determine whether this action is due to an effect at the hypothalamic level. Results showed that leptin, when administered directly into the brain third ventricle (3V), can stimulate (P < 0. 01) LH release in late juvenile animals at doses of 0.01-1.0 microg. A higher dose of 10 microg was ineffective in stimulating LH release. Immunoneutralization of luteinizing hormone-releasing hormone (LHRH) via 3V administration of LHRH antiserum to late juvenile animals indicated a hypothalamic site of action, since the leptin-induced LH release was blocked in the animals that received anti-LHRH, but not in the control animals that received normal rabbit serum. Leptin did not significantly stimulate LH release from animals in first proestrus, estrus, or diestrus. We also report that the serum levels of leptin increase (P < 0.05) during the late juvenile period of development, then decrease (P < 0.05) once the animal enters the peripubertal period. Collectively, our results show that leptin is capable of acting centrally to stimulate LH release, but only during late juvenile development; thus, we suggest the peptide likely plays a facilitatory role on late juvenile LH secretion, but does not drive the LHRH/LH releasing system to first ovulation and hence, sexual maturity.     

Age-related changes in the suppression of serum luteinizing hormone by estradiol-17beta in developing steers

Serum luteinizing hormone (LH) concentrations were measured at 4, 6, 8 and 10 mo of age in estradiol-17beta (E(2))-treated (n = 4) and contemporary control steers (n = 4). Serum LH was measured in samples collected at 30-min intervals starting at 0600 h for 12 h and for an additional 6 h following luteinizing hormone-releasing hormone (LHRH) injection. Estradiol-17beta suppressed mean serum LH concentrations at all ages (P<0.01), but it suppressed pulsatile release of LH only at 4 and 6 mo (P<0.01), not 8 and 10 mo of age. Luteinizing hormone release in response to LHRH, expressed as the area under the secretory curve, was larger and LH concentrations returned to pre-LHRH levels later in E(2)-treated steers (P<0.01). Peak LH concentrations after LHRH varied with age (P<0.05) but not E(2) treatment. These results suggest that E(2) suppression of LH in steers occurs at the hypothalamic level and developmental changes take place within the hypothalamicpituitary axis in absence of androgen feedback from the testis.     

A functional dimorphism in the response of the hypothalamic-pituitary axis of prepubertal rats to steroid treatment

In the present experiment we examined the circadian neural luteinizing hormone releasing hormone (LHRH) and serum luteinizing hormone (LH) response of prepubertal male and female rats under varying steroidal manipulations (Intact, Castrate, Castrate + estradiol 17 beta [E2] + oil and Castrate + E2 + progesterone[P]). Prepubertal males demonstrated greater and acyclic LHRH concentrations in both the medial basal hypothalamus (MBH) and preoptic-suprachiasmatic regions (POA-Sch) irrespective of steroid treatment. In steroid-treatment castrated male rats only the negative feedback action on serum LH levels were observed with maximal effect in animals injected with the combination E2 + P. In contrasts, prepuberal castrated females exhibited both inhibitory and stimulatory feedback actions on LH release following steroid treatment. Moreover, a distinctive, significant, progesterone-dependent increase in AM POA-Sch, but not MBH-LHRH concentrations was detected. These results demonstrate the existence of a functional sexual dimorphism in the positive feedback response of the POA-Sch-pituitary axis of prepubertal rats to progesterone treatment.