The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in female Syrian hamsters

Since melatonin injections administered near the end of the daily photoperiod influence both gonadal and thyroid hormones in the female hamster, the present study was designed to compare the effects of melatonin and hypothyroidism on the reproductive system and to determine whether thyroid status influenced the action of melatonin on the regulation of the hormones of reproduction. The effects of daily melatonin injections were determined in control hamsters, in hamsters rendered hypothyroid with thiourea, and in hypothyroid hamsters receiving thyroxin (T4) hormone replacement. As previously reported, melatonin injections disrupted estrous cyclicity, disrupted the normal pattern of gonadotropin secretion, and resulted in atrophy of the uterus and vagina. These changes coincided with depressed serum and pituitary prolactin (PRL), and depressed levels of estradiol. The effects of melatonin on uterus, vagina, ovary, and on gonadotropin levels were not prevented by T4 replacement, with the exception of a melatonin-induced increase in serum follicle-stimulating hormone (FSH). This suggested that the cessation of estrous cyclicity was not primarily a result of thyroid deficiency. Hypothyroidism, however, like melatonin, resulted in a reduced number of developing and mature follicles and corpora lutea in the ovaries, and in reduced uterine weight. It also produced follicular atresia, reduced the circulating levels of estradiol, and resulted in reduced incidence of estrus smears. T4 replacement, for 2 weeks, prevented the decline in mature follicles and corpora lutea, reduced the extent of follicular atresia, increased circulating levels of estradiol, and increased uterine weight. PRL and luteinizing hormone (LH) data also provided evidence for antagonistic effects of melatonin and T4 in female hamsters. These data raise the question whether melatonin-induced changes in circulating levels of T4 play a role in the seasonal cycles of reproductive competence in the female hamster.     

Reproductive effects of 6-chloromelatonin implants and/or injections in male and female Syrian hamsters (Mesocricetus auratus)

Adult female hamsters were injected each afternoon for 9 weeks with 2.5, 15 or 25 micrograms of melatonin or 6-chloromelatonin (CM). Each drug resulted in a significant dose-related depression in uterine, ovarian and anterior pituitary gland weights. Additionally, plasma and pituitary concentrations of prolactin fell with increasing dose of either indole whereas pituitary levels of LH and FSH were positively correlated with dose. There was no difference in effectiveness between the two drugs. Adult male hamsters treated for 10 weeks with daily afternoon injections of melatonin and a blank beeswax pellet had depressed testicular and accessory organ weights and plasma and pituitary concentrations of prolactin. Implantation of a 1 mg melatonin or CM beeswax pellet in hamsters concurrently receiving daily afternoon injections of melatonin prevented the organ weight and hormonal changes, except for plasma prolactin. Adult male hamsters treated for 10 weeks with daily afternoon injections of CM and a blank beeswax pellet had depressed reproductive organ weights and pituitary and plasma concentrations of prolactin; this depression in hormonal values and organ weights was totally prevented if the CM-injected hamsters were also bearing a beeswax-melatonin pellet. In conclusion, 6-chloromelatonin is as effective as melatonin with regards to antigonadotrophic and counter-antigonadotrophic effects in male and female Syrian hamsters.     

Exogenous T3 mimics long day lengths in Siberian hamsters

Siberian hamsters (Phodopus sungorus) exhibit seasonal cycles of reproduction driven by changes in day length. Day length is encoded endogenously by the duration of nocturnal melatonin (Mel) secretion from the pineal gland. Short-duration Mel signals stimulate reproduction and long-duration signals inhibit reproduction. The mechanism by which Mel signals are decoded at the level of neural target tissues remains uncharacterized. In Siberian hamsters, exposure to short day lengths or injections of Mel in long days results in a decrease in hypothalamic expression of type 2 iodothyronine deiodinase (Dio2) mRNA. Dio2 catalyzes the conversion of the thyroid hormone thyroxine to triiodothyronine (T3). Thus exposure to short and long day lengths should decrease and increase hypothalamic T3 concentrations, respectively. We tested the hypothesis that exogenous T3 administered to short-day hamsters would mimic exposure to long day lengths with respect to gonadal stimulation. Hamsters gestated and raised in short day lengths that exhibited photoinhibition of the testes were given daily subutaneous injections of T3 or saline vehicle for 4 wk beginning at week 12 of life. The results indicate that exogenous T3 induced gonadal growth in short-day hamsters and delayed spontaneous gonadal development by an interval equal to the number of weeks during which T3 was administered. T3 injections delayed gonadal regression if given coincident with the transfer of hamsters from long to short day lengths. These results suggest that T3 mimics long day exposure in Siberian hamsters and may serve as an intermediate step between the Mel rhythm and the reproductive response.     

Melatonin decreases estrogen receptor expression in the medial preoptic area of inbred (LSH/SsLak) golden hamsters.

Daily late afternoon injections of melatonin (25 micrograms/day s.c.) were found to reduce the number of cells expressing estrogen receptor immunoreactivity in the medial preoptic area of ovariectomized inbred (LSH/SsLak) golden hamsters. Employing immunocytochemical analysis with the H222 monoclonal antibody to the human estrogen receptor, we examined the effects of melatonin on estrogen receptor expression in the hypothalamus, particularly the medial preoptic area, of ovariectomized virgin female hamsters. Analysis of the results showed that melatonin administration induced a 50-70% decrease in numbers of estrogen receptor-immunoreactive neurons in the medial preoptic area of ovariectomized female hamsters. Furthermore, an overall qualitative decrease in the intensity of estrogen receptor immunoreactivity was observed. In intact regularly cycling female hamsters used to monitor the efficacy of melatonin treatment, there were significant reductions in the serum levels of FSH, LH, and prolactin as measured by radioimmunoassay and in uterine and pituitary weights after 8 wk of melatonin treatment. These results suggest that melatonin may exert its anti-reproductive effects in hamsters by modulating estrogen receptor levels in medial preoptic area neurons, thus influencing steroid feedback mechanisms.     

Effects of long-term treatment with melatonin or melatonin plus ectopic pituitary transplants on testicular LH/hCG and prolactin receptors in juvenile Syrian hamsters (Mesocricetus auratus)

Juvenile hamsters were injected daily with melatonin and some were also given transplants of 2 pituitaries under the kidney capsule. Weights of the testes and the accessory reproductive glands were reduced after 8 and after 12 weeks of melatonin treatment, but remained unaltered in animals treated with ectopic pituitary transplants. Levels of testicular LH/hCG receptors were significantly reduced by daily melatonin injections for 8 and 12 weeks. The presence of pituitary transplants in melatonin-injected hamsters prevented these reductions, and increased LH/hCG receptors above control levels. These changes in testicular LH/hCG receptors were closely related to alterations in serum prolactin concentration induced by melatonin and pituitary transplants. After 8, but not after 12 weeks of treatment, testicular prolactin receptor levels were reduced by melatonin and maintained by the presence of pituitary transplants. We conclude that: juvenile male hamsters become sensitive to the effects of daily melatonin injections when they reach maturity; daily melatonin injections can reduce the levels of testicular LH/hCG and prolactin receptors; and the effects of melatonin on LH/hCG and prolactin receptors are probably due to suppression of endogenous prolactin release.     

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.     

The effects of combined serotonin and dopamine precursor application during testicular photosensitivity vs photorefractoriness of the red headed bunting (emberiza bruniceps)

Abstract

A study of the temporal synergism of serotonergic and dopaminergic activity in the regulation of reproductive seasonality of photosensitive and photorefractory migratory Red headed bunting was undertaken. In experiment 1, groups of birds kept in natural day length (NDL) in their photosensitive phase (April) received daily injections of L‐DOPA (L‐dihydroxyphenylalanine, a dopamine precursor) at 8 and 12 hr after 5‐HTP (5 hydroxytryptophan, a serotonin precursor) administration. One control group received two daily injections of saline. The injections with 12‐hr temporal relation induced early recrudescence and full gonadal growth was achieved much in advance to that of control birds. The applications with 8‐hr temporal relation suppressed the testicular growth initially but later on this effect was eliminated by NDL of May‐June. In Experiment 2, photorefractory birds also received the treatments but the temporal relation of 5‐HTP and L‐DOPA had no effect on the regressed gonads of these birds.

This study indicates that injections with specific phase relations of dopamine and serotonin precursors may alter seasonal reproductive conditions only in the photosensitive phase but had no effect in photorefractory birds.     

Photoperiodic regulation of pulsatile luteinizing hormone secretion and adenohypophyseal gene expression in female golden hamsters.

LH concentrations were measured in serum collected at 10-min intervals from chronically ovariectomized female Syrian hamsters that had been maintained for 9 wk in stimulatory (long) or inhibitory (short) photoperiods. Short days reduced the number of detectable LH pulses during both the morning and the afternoon. Most short-day hamsters experienced a gradual afternoon rise in serum LH concentrations; this rise was not composed of multiple pulses. In separate groups of similarly treated hamsters, pituitary LH-beta mRNA abundance was significantly reduced by short-day exposure at both times of day even though serum LH concentrations rose in the afternoon. Estradiol treatment induced an afternoon surge of serum LH in both photoperiods, and eliminated the effect of photoperiod on LH-beta mRNA abundance in the afternoon. Serum prolactin (PRL) concentrations were not consistently influenced by day length in castrated hamsters with or without estrogen treatment, but PRL mRNA abundance was significantly suppressed by short-day exposure in all groups. The results indicate that day length exerts profound steroid-independent effects upon hypophyseal gene expression, and that the regulation of LH-beta mRNA abundance may be due to photoperiodic control of the neural GnRH pulse generator.     

Melatonin mediates alternation of seasonality in Syrian hamsters

The annual cycle of reproductive activity in the Syrian hamster, Mesocricetus auratus, is the result of interaction between seasonal changes in daylength (photoperiodism) and seasonal changes in responsiveness to daylength (seasonality). The present experiment was designed to investigate the role of the pineal gland and its hormone, melatonin, in the alternation of seasonality (scotosensitivity and scotorefractoriness). Male hamsters were maintained on short daylengths (10L:14D) to establish scotorefractoriness, and then they were transferred to long daylengths (14L:10D) for conversion to scotosensitivity (sensitive to short daylengths). Before transfer to long daylengths, some of the hamsters were pinealectomized and others were sham-operated or unoperated. Some of the pinealectomized hamsters received single daily melatonin or saline injections while on long daylengths. After 14 wk on long daylengths, the hamsters were transferred to short daylengths for 10 wk to test for conversion to scotosensitivity. Pinealectomized hamsters were given three daily melatonin injections while on short daylengths. Such treatment is known to promote gonadal regression in scotosensitive but not in scotorefractory hamsters. Examination of testes after the short daylength interval revealed that exposure of nonpinealectomized hamsters to long daylengths had reestablished scotosensitivity (regressed testes). Pinealectomized hamsters that received no melatonin replacement while on long daylengths remained scotorefractory (enlarged testes), whereas those that received single daily injections of melatonin during long daylengths were found to be scotosensitive. These results indicate that a daily pulse of melatonin during expsoure to long daylengths has an important role in reestablishing responsiveness (scotosensitivity) to short daylengths.     

Photoperiodic regulation of glutamatergic stimulation of secretion of luteinizing hormone in male Syrian hamsters.

It has been suggested that changes in endogenous glutamatergic stimulation of secretion of luteinizing hormone (LH) induced by photoperiod play a role in regulating seasonal cycles of reproductive activity. The aim of this study was to test the hypothesis that the glutamatergic control of the secretion of LH in the male Syrian hamster is sensitive to photoperiod, by determining whether the glutamate agonist N-methyl-D-aspartate (NMDA) could stimulate LH secretion in this species and, if so, to determine whether the response varied among animals exposed to different daylengths. In the first experiment, adult male hamsters were housed in either short day (8 h light: 16 h dark) for 6 weeks to induce testicular regression, or long days (16 h light: 8 h dark) to maintain testicular function, and the effects of systemic administration of NMDA on serum LH concentrations were determined. In the short-day hamsters, all s.c. doses of NMDA (25-75 mg kg-1 body weight) produced a robust rise in serum LH concentrations within 15 min. In the long-day hamsters, basal LH concentrations were higher than in short-day hamsters, but only the highest dose of NMDA produced a significant increase in LH concentrations, and the magnitude of this increment was less than those observed in short days. In hamsters in long days, the low doses of NMDA that did not significantly alter LH concentrations nevertheless significantly suppressed serum prolactin concentrations, demonstrating the efficacy of the drug. In hamsters in short days, serum prolactin concentrations were at the limit of detection of the assay, so no inhibitory effect of NMDA on prolactin secretion could be determined on this photoperiod. In the second experiment, the effects of a fixed dose of NMDA (50 mg kg-1 body weight) was tested at intervals in hamsters exposed to short days for a prolonged period such that their testes initially regressed, but then became scotorefractory and testicular recrudescence occurred. After 6 and 12 weeks in short days, NMDA stimulated LH secretion. However, after 24 weeks in short days when testicular recrudescence was complete, the response to NMDA was lost. A third experiment determined whether the reduced response to NMDA in hamsters on long days relative to those in short days might result from higher concentrations of circulating testosterone. Hamsters in long days were castrated to remove the influence of gonadal feedback, and the response to NMDA tested 3 weeks later when endogenous LH concentrations had risen to levels characteristic of the chronically castrated condition.(ABSTRACT TRUNCATED AT 400 WORDS)     

Circadian and Seasonal Variations of Plasma Insulin and Cortisol Concentrations in the Syrian Hamster, Mesocricetus Auratus

Circadian rhythms of plasma insulin, Cortisol, and glucose concentrations were examined in scotosensitive (reproductively sensitive to inhibitory effects of short daylengths) and scotorefractory male and female Syrian hamsters (Mesocricetus auratus) maintained on short (LD 10:14) and long (LD 14:10) daylengths. The baseline concentration (mean of all values obtained every 4 hr six times of day) of insulin was much greater in female than in male scotosensitive hamsters kept on short daylengths. These differences in insulin concentration may account for the observed heavy fat stores in female and low fat stores in male scotosensitive hamsters kept on short daylengths. The baseline concentrations of Cortisol were approximately equal in both scotosensitive and scotorefractory males held on short and long daylengths, but were relatively low in females held on short daylengths and especially high in scotorefractory females held on long daylengths.

The plasma concentrations of both cortisol and insulin varied throughout the day in many of the groups tested. However, the variations were not equivalent. The circadian variations of cortisol were similar irrespective of sex, seasonal condition and daylength. Peak concentrations generally occurred about 12 hr after light onset. In contrast, the circadian variations of insulin differed markedly. For example in male hamsters, robust daily variations were found in scotosensitive hamsters held on short daylengths but not on long daylengths and in scotorefractory hamsters held on long daylengths but not on short daylengths. Furthermore, the daily peak occurred during the light in the scotosensitive hamsters and during the dark in the scotorefractory animals. Neither the daily feeding pattern (about 60% consumed during dark) nor the daily variations of glucose concentration varied appreciably with seasonal condition or daylength. They do not appear to determine nor directly reflect the variations in cortisol and glucose concentrations. It is postulated that the daily rhythms of cortisol and insulin are regulated by different neural pacemaker systems and that changes in the phase relations of circadian systems account in part for seasonal changes in body fat stores.     

Delayed puberty caused by hyperthyroidism in ram lambs is not a result of suppression in body growth

Over a period of 8 weeks ram lambs (16 weeks old) were made hyperthyroidal (serum thyroxine approximately equal to 150 ng/ml, compared with control approximately equal to 48 ng/ml) by daily subcutaneous injections of thyroxine or maintained at a constant body weight by restriction of the feed intake. Hyperthyroidal and restricted-intake lambs remained at a constant body weight during the period of treatment whilst control rams gained body weight. Testicular growth was normal in restricted-intake lambs but was suppressed in hyperthyroidal animals. Hyperthyroidism, but not feed restriction, was also associated with decrease in LH pulse frequency (1.3 +/- 0.3/12 h compared with controls 4.8 +/- 0.9/12 h. Hyperthyroidal lambs showed normal LH responses to exogenous LHRH. After cessation of treatment testicular growth continued to be suppressed for up to 16 weeks in previously hyperthyroidic rams; thereafter testes began to increase in size but at 30 weeks after treatment were still smaller than those of control rams. It is concluded that elevated thyroxine concentrations directly influence sexual maturation in ram lambs through actions at hypothalamic and/or higher brain centres which control LH secretion. Transient hyperthyroidism during sexual maturation may cause permanent impairment of sexual development.     

Naloxone administration to female hamsters advances puberty by enhancing luteinizing hormone release

In the female hamster, a daily rhythm of gonadotropin release begins almost 3 weeks prior to the initiation of 4-day estrous cycles. A temporal relationship exists between the onset of this cyclic release of gonadotropin and age at puberty. We hypothesized that since opiate agonists depress circulating gonadotropins and antagonists increase them in both adult and immature rodents, endogenous opiates may influence the mechanism controlling cyclical gonadotropin release in the prepubertal female hamster and thus affect rate of sexual maturation and hence the age at puberty. This proposal was tested by chronic administration of naloxone (NAL), an opiate receptor antagonist. We predicted that NAL might induce the early initiation of daily surges of luteinizing hormone (LH) if endogenous opiates inhibit sexual maturation. Naloxone was injected daily (50 mg/kg body wt) at about 1300 hr from Days 1 through 17 of age. The NAL injections increased serum LH and significantly advanced the age at which first estrus vaginal discharge was observed (32 vs 38 days for saline-injected controls in Experiment I and 31 vs 37 days in Experiment II). However, the NAL injections did not correspondingly advance the age of initiation of endogenously generated daily cycles of circulating LH. We conclude that blockade of opiate receptors accelerates sexual maturation by directly inducing the release of LH and not by advancing the age of initiation of endogenous gonadotropin surges.     

Interrelationship between estrogen and thyroxine on the release of luteinizing hormone and gonadotropin-releasing hormone in vitro

The present experiments were designed to study the interaction between estradiol benzoate (EB) and thyroxine (T4) given in vivo on the responsiveness of pituitary luteinizing hormone (LH) to gonadotropin-releasing hormone (GnRH) and the release of GnRH in vitro. Ovariectomized-thyroidectomized (Ovx-Tx) rats were injected s.c. with saline or T4 (2 micrograms/100 g b.wt), and oil or EB (0.1 microgram) once daily for 40 days following a 2 x 2 factorial design. All animals were then decapitated and blood samples were collected. Anterior pituitaries (APs) were incubated in vitro with and without 0.1 ng GnRH at 37 degrees C for 4 h. Mediobasal hypothalami (MBHs) were excised and then incubated with and without APs from Ovx donor rats. Concentrations of LH and GnRH in the medium and that of LH in the serum were measured by radioimmunoassay. The LH level in media containing MBHs and donor APs was used as the index of bioactive GnRH release. In Ovx-Tx rats, T4 injections reduced the serum LH concentration, the pituitary LH response to GnRH, and the bioactive as well as the immunoreactive GnRH release. The serum LH levels and the spontaneous as well as the GnRH-stimulated release of LH in vitro were suppressed in Ovx-Tx rats following administration of EB. By contrast, the serum LH concentration, as well as pituitary LH response to GnRH and GnRH release in vitro, were higher in the group treated with both T4 and EB than in that treated with saline and EB. These results suggest that the differential changes in the LH secretion after thyroidectomy of Ovx versus non-Ovx rats are due to an antagonistic effect between T4 and estrogen on the response of pituitary LH to GnRH, and the release of GnRH.     

Chemosensory stimulation of luteinizing hormone secretion in male Siberian hamsters (Phodopus sungorus)

Male Siberian hamsters (Phodopus sungorus) housed in long days (LD), but not short days (SD) release luteinizing hormone (LH) when exposed to females. This study examined whether this response is specific to a female and identifies the source of a stimulus that induces LH release. Serum concentrations of LH, testosterone (T), follicle stimulating hormone (FSH), and cortisol were examined in all experiments. T concentrations mirrored the LH response; FSH and cortisol were unchanged in response to all stimuli. Exposure to an LD female, irrespective of her reproductive status, but not an SD female, elicited LH release. Exposure to another male did not trigger LH release. Males released LH when allowed physical contact with an anesthetized female, but not when separated from a normally active female, suggesting that tactile or nonvolatile chemosensory stimuli elicit LH release. Urine and secretions collected from the vagina as well as oral, midventral, perineal, and rectal glands, elicited marked behavioral responses in male P. sungorus. Despite these behavioral responses, only feces from females elicited LH release in males. Males released LH in response to feces extracted from the rectum and to cotton swabs that had been rubbed against the rectal mucosa, suggesting that a component of rectal secretions may trigger LH release in male Siberian hamsters. Taken together, these data and previous data from our laboratory indicate that both the production of and the response to a pheromone that triggers the selective release of LH is regulated by day length.     

Chronic exposure to short photoperiod inhibits free thyroxine index and plasma levels of TSH, T4, triiodothyronine (T3) and cholesterol in female Syrian hamsters

1. Chronic exposure of female Syrian hamsters (Mesocricetus auratus) for 9 weeks to a short photoperiod (10L:14D) depressed the pituitary-thyroid axis as indicated by a drop in circulating titers of thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and the free thyroxine index (FT4I) compared to animals maintained under long photoperiodic conditions (14L:10D). 2. Short day treatment also reduced plasma cholesterol levels. 3. Neither plasma triglycerides, glucose nor growth hormone (GH) levels differed between hamsters exposed to short or long daily photoperiods.     

Pre-exposure to female chemosignals or intracerebral GnRH restores mating behavior in naive male hamsters with vomeronasal organ lesions

Chemosensory input is essential for mating in male hamsters and the vomeronasal organ is critical to mating in naive males. In studies to investigate the convergence of vomeronasal chemosensory input and the neurohormone gonadotrophin releasing hormone (GnRH), we have unexpectedly found that pre-exposure to pheromone-containing chemosignals from female hamsters will also eliminate mating deficits normally seen in naive male hamsters with vomeronasal organs removed (VNX). In the present studies, naive-intact and naive-VNX male hamsters were given intracerebroventricular injections of GnRH or saline and exposed to female pheromones found in hamster vaginal fluid (HVF) or to water 40 min prior to a 5 min mating test. VNX males given saline injections and exposed to water had severe mating deficits, but VNX males given saline injections and exposed to HVF mated normally. As shown previously, males given GnRH injections and exposed to water also mated normally. HVF exposure prior to a mating test apparently acted to compensate for the lack of vomeronasal input in these males.     

Daily rhythms of pituitary-ovarian function in the immature hamster are independent of adrenal and pineal influence

In female hamsters, the daily rhythm of LH appeared on the 15th or 16th day after birth with a peak occurring at about 16:00 h (14L:10D, lights on 06:00 h). Progesterone concentrations increased and became rhythmic a few days later. In serum samples collected at 14, 16, 18, 20, 25, 30, 40 and 60-62 days of age between 13:00 and 23:00 h, significant rhythms of serum cortisol and corticosterone concentrations were not detected before 25 days of age; furthermore, the phase of the rhythms did not stabilize to the adult pattern until about 40 days of age. As in the adult, significant rhythms were present in both sexes and the levels of cortisol were greater than those of corticosterone. Injection of pig ACTH (50 i.u./kg body wt, i.p.) significantly increased serum cortisol by 10 days of age, but corticosterone did not respond until 25 days of age. Thus, for cortisol at least, the appearance of 24-h rhythms in the serum is probably not dependent on the ability of the adrenal to respond to ACTH. Ovariectomy had no effect on the late afternoon surge of serum cortisol; similarly, adrenalectomy of immature females did not abolish the surge of LH. Ovariectomy did not alter the daily rhythm of pineal melatonin content and pinealectomy had no effect on the daily afternoon surge of LH. These results demonstrate functional independence of circadian rhythms in the pituitary-gonadal axis and the pituitary-adrenal axis of the immature hamster and also independence of daily rhythms of pineal melatonin and pituitary release of LH.     

Alpha-fetoprotein serum levels and the development of estrogen-sensitive cell multiplication in the hamster uterus

Subcutaneous injections of 5 or 25 micrograms estradiol-17 beta (E2)/kg in ovariectomized adult hamsters produced substantial increases in uterine wet weight, protein content and the mitotic indices of the glandular and luminal epithelia. However, no significant increase was seen in total uterine DNA. Intact hamsters from 2 to 25 days of age received a daily subcutaneous injection of 5 micrograms E2/kg for 2 consecutive days. Significant increases in uterine wet weight and protein content first occurred at 8 and 17 days, respectively. No significant increase was observed in uterine DNA. In a separate experiment, hamsters between 2 and 20 days of age received one subcutaneous injection of 5 micrograms E2/kg. Mitotic indices in the stroma were increased at 6 and 10 days of age. Mitotic indices in the luminal epithelium were significantly increased only at 6 days of age. Rocket immunoelectrophoresis revealed a sharp decline in serum alpha-fetoprotein (AFP) concentrations after 2 days of age. Estradiol concentrations in the sera of immature hamsters gradually decreased from 55 pg/ml at 0 days of age to 17 pg/ml at 20 days of age. These results provide a quantitative analysis of the effects of E2 upon cell proliferation in the hamster uterus. The correlation of declining AFP levels and the incipience of the mitotic response to estrogen suggests that AFP may directly inhibit estrogen-sensitive cell multiplication in the neonate. Other possible causes for the lack of a mitotic response in the uterus of the newborn hamster to the administration of E2 are also discussed.     

Adrenal hormones mediate melatonin-induced increases in aggression in male Siberian hamsters (Phodopus sungorus)

Among the suite of seasonal adaptations displayed by nontropical rodents, some species demonstrate increased territorial aggression in short compared with long day lengths despite basal levels of testosterone. The precise physiological mechanisms mediating seasonal changes in aggression, however, remain largely unknown. The goal of the present study was to examine the role of melatonin, as well as adrenal hormones, in the regulation of seasonal aggression in male Siberian hamsters (Phodopus sungorus). In Experiment 1, male Siberian hamsters received either daily (s.c.) injections of melatonin (15 microg/day) or saline 2 h before lights out for 10 consecutive days. In Experiment 2, hamsters received adrenal demedullations (ADMEDx), whereas in Experiment 3 animals received adrenalectomies (ADx); control animals in both experiments received sham surgeries. Animals in both experiments subsequently received daily injections of melatonin or vehicle as in Experiment 1. Animals in all experiments were tested using a resident-intruder model of aggression. In Experiment 1, exogenous melatonin treatment increased aggression compared with control hamsters. In Experiment 2, ADMEDx had no effect on melatonin-induced aggression. In Experiment 3, the melatonin-induced increase in aggression was significantly attenuated by ADx. Collectively, the results of the present study demonstrate that short day-like patterns of melatonin increase aggression in male Siberian hamsters and suggest that increased aggression is due, in part, to changes in adrenocortical steroids.