Splenic denervation blocks leptin-induced enhancement of humoral immunity in Siberian hamsters (Phodopus sungorus)

Nontropical rodents have evolved adaptations to maximize winter survival, including alterations in reproduction, energy balance and immunity. Short-day-housed Siberian hamsters display reductions in body fat and decreases in humoral immunity compared with long-day hamsters. The hormone leptin, secreted by adipose tissue, varies in response to changes in body fat and has been implicated in photoperiodic changes in immunity. In addition, the metabolic effects of this hormone appear to be mediated by the sympathetic nervous system (SNS). Very little is known, however, regarding the role of the SNS in regulating the effects of leptin on immunity. The goal of the present study was to examine the effects of splenic denervation on leptin-induced immune enhancement of short-day Siberian hamsters. Male hamsters were housed in long (LD 16:8) or short days (LD 8:16) for 10 weeks. Half of the animals in each photoperiod received surgical denervations of the spleen; the remaining animals received sham operations. In addition, animals in each group were implanted with osmotic minipumps containing either leptin or vehicle. Hamsters were then injected with keyhole limpet hemocyanin (KLH) and serum anti-KLH antibody production was assessed. Short-day hamsters displayed decreased humoral immunity in short versus long days; leptin attenuated the short-day decrease but did not enhance immunity of long-day hamsters. Furthermore, splenic denervation blocked the leptin-induced increase in immunity in short-day hamsters. Collectively, these data suggest that leptin plays an important role in regulating seasonal changes in humoral immunity of Siberian hamsters and the effects of leptin occur, at least in part, via changes in the SNS innervation of lymphoid tissue.     

RFamide-related peptide gene is a melatonin-driven photoperiodic gene

In seasonal species, various physiological processes including reproduction are organized by photoperiod via melatonin, but the mechanisms of melatonin action are still unknown. In birds, the peptide gonadotropin-inhibiting hormone (GnIH) has been shown to have inhibitory effects on reproductive activity and displays seasonal changes of expression. Here we present evidence in mammals that the gene orthologous to GnIH, the RFamide-related peptide (RFRP) gene, expressed in the mediobasal hypothalamus, is strongly regulated by the length of the photoperiod, via melatonin. The level of RFRP mRNA and the number of RFRP-immunoreactive cell bodies were reduced in sexually quiescent Syrian and Siberian hamsters acclimated to short-day photoperiod (SD) compared with sexually active animals maintained under long-day photoperiod (LD). This was contrasted in the laboratory Wistar rat, a non-photoperiodic breeder, in which no evidence for RFRP photoperiodic modulation was seen. In Syrian hamsters, the reduction of RFRP expression in SD was independent from secondary changes in gonadal steroids. By contrast, the photoperiodic variation of RFRP expression was abolished in pinealectomized hamsters, and injections of LD hamsters with melatonin for 60 d provoked inhibition of RFRP expression down to SD levels, indicating that the regulation is dependent on melatonin. Altogether, these results demonstrate that in these hamster species, the RFRP neurons are photoperiodically modulated via a melatonin-dependent process. These observations raise questions on the role of RFRP as a general inhibitor of reproduction and evoke new perspectives for understanding how melatonin controls seasonal processes via hypothalamic targets.     

Melatonin and the coding of day length in male Syrian hamsters

Two experiments investigated the response of the pituitary-gonadal axis of pinealectomized male Syrian hamsters to programmed systemic administration of melatonin. In the first experiment, castrated male Syrian hamsters were housed in a short photoperiod (8L:16D) and maintained on subcutaneous testosterone implants for 7 weeks. These males were then pinealectomized or sham-pinealectomized and their testosterone capsules removed. Daily infusions of melatonin 250 ng/infusion) or its vehicle were administered for 3 weeks; infusion duration was long (11 or 12 hr) or short (6 hr). Measurement of serum luteinizing hormone (LH) following this 3-week period indicated that long-duration melatonin infusions mimicked short-day conditions (LH levels were low), but short-duration infusions did not (LH levels were significantly elevated). In the second experiment, pinealectomized, gonadally intact males were housed in a 12L:12D photoperiod and injected once daily with melatonin or its vehicle, either 3 or 5 hr after dark onset for 11 weeks. These times were chosen to coincide with the light:dark cycle phase that according to published reports is optimally responsive to exogenous melatonin for the induction of short-photoperiodic effects. Melatonin injections did not induce gonadal regression in pinealectomized hamsters. Melatonin and vehicle-treated males responded similarly; their testis widths and serum testosterone levels were not significantly different at the end of the experiment. These results support the hypothesis that the duration of melatonin secretion each night is an important variable in conveying photoperiodic information, but that the circadian phase during which melatonin is present is not.     

Effects of Photoperiod or Exogenous Melatonin Administration on the Activity of N-Acetyltransferase and Hydroxyindole-O-Methyltransferase and the Melatonin Content of the Harderian Gland of Two Strains of Female Syrian Hamsters

The activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) and the melatonin concentration of the Harderian glands of two strains of Syrian hamster females (outbred and inbred LSH/SsLak) exposed to two different photoperiods (14:10 h and 8:16 h) were studied. The Harderian glands of the inbred hamsters showed greater NAT activity than those of the outbred animals. On the other hand, the glands of the outbred hamsters exhibited higher HIOMT activity and melatonin content than those of the inbred LSH/SsLak. Short photoperiod exposure, which produced gonadal regression in the inbred but not in the outbred hamsters, decreased the NAT activity in the inbred animals to the levels of the outbred. HIOMT activity was not affected by the lighting conditions. After the exposure to short days, the melatonin content of the inbred hamster Harderian glands increased to that in the outbred animals. Daily melatonin injections, which caused gonadal regression in the LSH/SsLak but not in the outbred hamsters, did not stimulate the effect of the short photoperiod on the Harderian gland NAT activity and melatonin content of the inbred hamsters.     

Interactive Effects of Stress and Photoperiod History on Gonadal Condition in Male Syrian Hamsters

A study of the effects of melatonin injections given to male Syrian hamsters (Mesocricetus auratus) late in the light phase in a 14L:10D photoperiod included control, oil-injected hamsters that had been transferred from a 16L:8D photoperiod. Many oil-injected hamsters underwent gonadal regression under these conditions. A literature review indicated that endocrine effects of 'control' injections are fairly common but that they might depend on previous photoperiodic history. A second study found that hamsters born and raised in 16L:8D had larger testes at 150 days of age than those raised in 14L:10D. Transfer from 16L:8D to 14L:10D caused some unhandled hamsters to show gonadal regression while transfer to 14L:10D combined with daily oil injections caused most hamsters to undergo gonadal regression. Injections in animals maintained in 14L:10D throughout the study did not cause gonadal regression. These results indicate that stress effects can confound interpretation of drug treatments that require daily injections. They also demonstrate that the endocrine system of male Syrian hamsters distinguishes two photoperiods that are longer than the critical daylength (12.5 h). The effects of shortening daylengths may be potentiated by environmental stressors; together these may trigger gonadal regression at variable annual phases in anticipation of the critical daylength.     

Photoperiod History, Melatonin, and Reproductive Responses of Male Syrian Hamsters

The action of melatonin (MEL) in mediating photoperiodic history (PPH) effects among male Syrian hamsters was investigated. In Exp. 1, pineal intact males in LD 14:10 received daily injections of MEL (15 micrograms) or ethanol:saline vehicle (SAL) 1 h before lights off for 8 wk to generate two groups experiencing identical photoperiods but distinctly different MEL histories. Following the cessation of injections, males were transferred to either LD 12:12 or LD 8:16 for 8 wk to evaluate whether their reproductive response to the new photoperiod would be more influenced by prior PPH or prior MEL history; MEL history was the significant variable. LD 12:12 caused gradual recrudescence in hamsters that were gonadally regressed following MEL injections. In contrast, LD 12:12 caused gonadal regression in hamsters that had large testes following SAL injections. Exp. 2 evaluated whether PPH influences might be mediated by aftereffects on the period (tau) of the circadian pacemaker regulating many behavioral and physiological rhythms. Pineal intact hamsters were exposed to long or short T cycles consisting of an 8 h photoperiod, repeated every 24.67 h (long T) or 23.33 h (short T) to mimic the aftereffects generated by short or long photoperiods. After 5 wk in these T-cycle conditions, all males were transferred to LD 12:12 for 11 wk. The reproductive response to LD 12:12 was modestly influenced by T-cycle history, even though each T-cycle generated different patterns of entrainment to LD 12:12. These findings support the hypothesis that the response of the reproductive system of male hamsters to an intermediate-duration photoperiod depends upon the duration of nocturnal melatonin secretion associated with hamsters' previous PPH.     

Sustained melatonin treatment blocks body mass, pelage, reproductive, and fever responses to short day lengths in female Siberian hamsters

Winter imposes physiological challenges on individuals including increased thermoregulatory demands, risk of infection, and decreased food availability. To survive these challenges, animals living outside the tropics must appropriately distribute their energetic costs across the year, including reproduction and immune function. Individuals of many species use the annual cycle of changing day lengths (photoperiod), which is encoded by the nightly duration of melatonin secretion, to adjust physiology. Siberian hamsters exposed to short days (SD) (long nights/prolonged endogenous melatonin secretion) enhance some aspects of immune function, but curtail other energetically expensive immune functions including the febrile response. The purpose of this study was twofold. First, we determined whether sustained melatonin treatment would inhibit the development of the SD phenotype in female hamsters as it does in males. Second, we examined whether the SD attenuation of fever would be blocked by continuous exposure to exogenous melatonin. Hamsters were implanted with melatonin or empty capsules, housed in either long days (LD) or SD for 8-9 weeks, and then challenged with lipopolysaccharide; body temperature and locomotor activity were recorded. Unlike hamsters with empty capsules, hamsters with melatonin implants did not respond to SD and maintained a LD phenotype including summer-like spleen, uterine and body masses, and pelage characteristics. Further, sustained melatonin treatment blocked the SD attenuation of febrile responses and prolonged the behavioral components of the sickness response. These results suggest that the daily fluctuations in endogenous melatonin may be masked by continuous exposure to exogenous melatonin, thus inhibiting functional photoperiodic responses to SD.     

Hormonal Modulation of Pineal-Mediated Seasonal Events: Effects of Thyroid or Gonadal Manipulations

The ability of various manipulations of the endocrine system to affect pineal-mediated events was examined in the present studies. Male Syrian hamsters were analyzed for pineal-induced gonadal regression and depressions in serum thyroxine and testosterone levels after treatments which altered thyroid or gonadal function. Hamsters were thyroidectomized, received thyroxine implants (5 mg), or were thyroidectomized plus implanted with thyroxine. The animals were exposed to short photoperiods (10L:14D) for 9 wk, and plasma hormone levels and gonadal status were determined at the end of the experimental period. Likewise, hamsters were castrated, received testosterone implants (5 mg), or were castrated plus implanted with testosterone, and subsequently were exposed to short photoperiods for 9 wk. These animals' responses to photoperiod exposure were compared to animals which received identical hormonal treatments but remained in long photoperiod (14L:10D). All of the hamsters responded to the photoperiodic treatments equally, regardless of the hormonal treatment. The results of these studies indicate that experimentally induced alterations in plasma thyroxine or testosterone levels are unable to prevent or attenuate the ability of the pineal to elicit gonadal regression in response to short photoperiod exposure.     

Melatonin regulates type 2 deiodinase gene expression in the Syrian hamster

In seasonal species, photoperiod organizes various physiological processes, including reproduction. Recent data indicate that the expression of type 2 iodothyronine deiodinase (Dio2) is modulated by photoperiod in the mediobasal hypothalamus of some seasonal species. Dio2 is believed to control the local synthesis of bioactive T(3) to regulate gonadal response. Here we used in situ hybridization to study Dio2 expression in the hypothalamus of a photoperiodic rodent, the Syrian hamster. Dio2 was highly expressed in reproductively active hamsters in long day, whereas it was dramatically reduced in sexually inhibited hamsters maintained in short day. This contrasted with the laboratory rat, a nonphotoperiodic species, in which no evidence for Dio2 photoperiodic modulation was seen. We also demonstrate that photoperiodic variations of Dio2 expression in hamsters are independent from secondary changes in gonadal steroids. Studies in pinealectomized hamsters showed that the photoperiodic variation of Dio2 expression is melatonin dependent, and injections of long day hamsters with melatonin for only 7 d were sufficient to inhibit Dio2 expression to that of short day levels. Finally, because in some seasonal species thyroid hormones are involved in photorefractoriness, we examined Dio2 expression in short day-refractory hamsters and found that Dio2 mRNA levels remained low despite full reproductive recrudescence. Altogether, these results demonstrate that in the Syrian hamster Dio2 is photoperiodically modulated via a melatonin-dependent process. Furthermore, refractoriness to photoperiod in hamsters appears to occur independently of Dio2. These results raise new perspectives for understanding how thyroid hormones are involved in the control of photoperiodic neuroendocrine processes.     

Elevated ambient temperature retards the atrophic response of the neuroendocrine-reproductive axis of male Syrian hamsters to either daily afternoon melatonin injections or to short photoperiod exposure

Adult male Syrian (golden) hamsters, maintained under either 22 +/- 2 or 32 +/- 2 degrees C, were treated with 8 or 11 weeks of exposure to either long photoperiod (14:10), short photoperiod (8:16), or to long photoperiod with a daily afternoon melatonin injection. By 8 weeks, the animals kept at 22 degrees C and treated with daily afternoon melatonin injection exhibited a dramatic reduction in testicular and accessory sex organ weight, but the animals kept at 32 degrees C and treated in the same way exhibited only slight decreases in testicular and accessory organ weights. Short photoperiod caused a slight decrease in testicular and accessory organ weights of hamster kept at 22 degrees C, while it had no significant effects on reproductive organ weights of the animals maintained under 32 degrees C. By 11 weeks, the daily afternoon melatonin injection elicited further reduction in testicular and accessory organ weights of the animals maintained under both 22 and 32 degrees C. However, the reduction in animals kept at 32 degrees C was not as great as that in animals kept at 22 degrees C. Although short photoperiod caused an obvious decline in reproductive organ weights of the animals at 22 degrees C, only a slight decrease was seen in hamsters at 32 degrees C. As with reproductive organ weights, testosterone levels were depressed more rapidly and completely in animals maintained at 22 degrees C. These results indicate that elevated ambient temperature changes the rate at which the gonads of hamsters regress in response to daily afternoon melatonin injections or short photoperiod.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naloxone-induced secretion of LH in the male Syrian hamster: modulation by photoperiod and gonadal steroids

The role of endogenous opiates in the regulation of photoperiodically induced testicular regression was studied in the male Syrian hamster. In reproductively active hamsters exposed to a long photoperiod (LD; 16 h light: 8 h darkness) or to short days (SD; 8 h light: 16 h darkness) for 20 weeks or to SD after pinealectomy, administration of naloxone, a competitive opiate receptor antagonist, at doses of 2.5-20 mg/kg, significantly increased serum LH concentrations. In marked contrast, these doses of naloxone did not produce any change in LH levels in reproductively quiescent hamsters exposed to SD for 8 weeks. The influence of gonadal steroids on the LH response to naloxone was studied in hamsters castrated or castrated and implanted s.c with a capsule containing testosterone. Naloxone did not induce LH release in castrated hamsters maintained in LD or in SD, but this response was restored in LD but not SD when serum testosterone concentrations were maintained at levels similar to those observed in intact reproductively active hamsters. These results show that inhibition of reproduction by the photoperiod prevents naloxone-induced LH release in the male hamster. This lack of response to naloxone is not due, however, to the lower testosterone titres present in these animals compared with reproductively active animals. Responsiveness to naloxone can be restored when the animal is rendered insensitive to the inhibitory photoperiod either by removal of the pineal gland or by induction of photorefractoriness by extended exposure to SD.     

In vitro melatonin treatment enhances splenocyte proliferation in prairie voles

The seasonal effects of photoperiod on reproduction are mediated by melatonin, and it is hypothesized that increased immune function in short days is due to the increase in the duration of nightly melatonin secretion. Melatonin can act both directly and indirectly on target tissue within the immune system. The present study sought to tease apart the direct and indirect effects of melatonin on one aspect of immune function by examining the influence of in vitro melatonin on splenocyte proliferation in female prairie voles held in long (LD 16:8) or short (LD 8:16) days. Splenocyte proliferation in response to the T-cell mitogen concanavalin A was enhanced by the addition of melatonin in vitro, as compared to cultures receiving no melatonin. Body mass increased in short-day housed prairie voles, indicating that the animals were responsive to photoperiod. However, photoperiod did not affect splenocyte proliferation in the present study. These results support the hypothesis that melatonin exerts a direct effect on splenocyte proliferation, potentially via high-affinity melatonin receptors localized on splenocytes. The findings also indicate that, irrespective of photoperiod, melatonin exerts direct effects on splenocytes to enhance immune function.     

Effects of afternoon injections of melatonin in hypothyroid male Syrian hamsters

Male Syrian hamsters were kept under either 14 h light/10 h dark (lights on at 06.30 h) or 2 h light/22 h dark (lights on at 14.30 h) photoperiods. Groups of hamsters under each photoperiod were rendered hypothyroid by addition of 0.4% thiourea to the drinking water. These hamsters received, in addition, either a daily evening injection of saline or a daily injection of 25 micrograms melatonin in saline. Groups of intact controls and pinealectomized control hamsters were also maintained under the two photoperiodic conditions. After 10 weeks under the different conditions the hamsters were killed by decapitation, and serum samples assayed for thyroxin, thyroid-stimulating hormone (TSH), and prolactin (PRL). Pituitary extracts were assayed for TSH and PRL. Hypothyroidism in hamsters receiving thiourea was confirmed by radio-immunoassay data showing low serum thyroxin and greatly elevated serum TSH concentrations. Melatonin injections resulted in significant depression of serum TSH in thiourea-treated hamsters under short photoperiod compared to saline-injected controls. Both melatonin injections and short photoperiod resulted in a significant reduction of pituitary TSH in hamsters on thiourea compared to values obtained from similarly treated animals under the 14 h light/10 h dark photoperiod. Hypothalamic concentrations of thyrotropin-releasing hormone (TRH) were significantly elevated by melatonin injections and by short photoperiodic conditions, but not by thiourea administration. The short photoperiod resulted in testicular involution which was completely reversed by pinealectomy and partially reversed (to 53% of controls) by thiourea treatment. Involution of gonads was complete in thiourea-treated animals under short photoperiod, if they received melatonin injections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exogenous kisspeptin does not alter photoperiod-induced gonadal regression in Siberian hamsters (Phodopus sungorus).

In order to reproduce successfully, animals must integrate multiple environmental cues to synchronize breeding with favorable conditions. In temperate, seasonally breeding rodents, photoperiod acts as the primary seasonal cue. Long days are associated with reproductive development and maturation of the gonads whereas short days induce gonadal regression. The neuropeptide kisspeptin has potent stimulatory effects on reproductive development. Kisspeptin potently stimulates GnRH release and kisspeptin expression co-varies with photoperiod in seasonally breeding animals. Here we tested the hypothesis that reproductive involution in response to inhibitory day lengths results from reduced kisspeptin stimulation of the reproductive axis in seasonally breeding Siberian hamsters (Phodopus sungorus). If true, gonadal regrowth should be hastened by kisspeptin treatment in regressed hamsters and prevented in hamsters by treatment prior to and during regression. In Experiments 1 and 2 we tested the ability of kisspeptin to reverse gonadal regression. In Experiment 1, reproductively regressed hamsters received chronic kisspeptin via osmotic mini-pumps for 4 weeks. In Experiment 2, daily injections of kisspeptin were administered to regressed hamsters for 6 weeks. In Experiment 3, the ability of kisspeptin to block gonadal regression was tested; hamsters transferred to short days received daily injections of kisspeptin for 6 weeks. In all three studies, short-day animals receiving exogenous kisspeptin did not differ from short-day controls. Collectively, these results provide evidence that mechanisms in addition to those that converge on the kisspeptin system are likely critical for seasonal changes in the reproductive axis.     

Kisspeptin: A key link to seasonal breeding

In seasonal species, photoperiod (i.e. daylength) tightly regulates reproduction to ensure that birth occurs at the most favorable time of year. In mammals, a distinct photoneuroendocrine circuit controls this process via the pineal hormone melatonin. This hormone is responsible for the seasonal regulation of reproduction, but the anatomical substrate and the cellular mechanism through which melatonin modulates sexual activity is far from understood. The Syrian hamster is widely used to explore the photoneuroendocrine system, because it is a seasonal model in which sexual activity is promoted by long summer days (LD) and inhibited by short winter days (SD). Recent evidences indicate that the products of the KiSS-1 gene, kisspeptins, and their specific receptor GPR54, represent potent stimulators of the sexual axis. We have shown that melatonin impacts on KiSS-1 expression to control reproduction in the Syrian hamster. In this species, KiSS-1 is expressed in the antero-ventral-periventricular and arcuate nuclei of the hypothalamus at significantly higher levels in hamsters kept in LD as compared to SD. In the arcuate nucleus, the downregulation of KiSS-1 expression in SD appears to be mediated by melatonin and not by secondary changes in gonadal hormones. Remarkably, a chronic administration of kisspeptin restores testicular activity in SD hamsters, despite persisting photoinhibitory conditions. Overall, these findings are consistent with a role of KiSS-1/GPR54 in the seasonal control of reproduction. We propose that the photoperiod, via melatonin, modulates KiSS-1 neurons to drive the reproductive axis.     

Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus)

The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects.     

Regulation of the androgen receptors in the Harderian gland of the male Syrian hamster: Influence of photoperiod, castration, and chronic melatonin treatment

Male Syrian hamsters that were exposed for 8 weeks to short photoperiod (LD 10:14) or treated with melatonin in the late afternoon under long photoperiod conditions (LD 14:10) had a significantly higher content of androgen receptors in the Lipidex-purified soluble fractions isolated from the Harderian glands as compared to the long photoperiod (LD 14:10) exposed controls. Simultaneous computer-assisted analyses of all series of saturation and competition experiments revealed that the numerical value of the apparent Kd, as determined by using the synthetic androgen R-1881 (methyltrienolone), was not different between the experimental groups, and ranged from 0.050 to 0.067 nM. Of the principal natural androgens, testosterone (T) was most potent in inhibiting methyltrienolone binding to the receptor (Ki values from 0.33 to 0.55 nM), and 5 alpha-dihydrotestosterone (DHT) and delta 4-androstenedione (AD) were less effective (Ki values between 1 and 1.9 nM). In the hypothalami and pituitaries of the same animals, used in parallel control assays, DHT was twice as potent as T. Short-term castration (24 hr post-orchidectomy) did not result in significant changes in the receptor binding characteristics. Following 8 weeks exposure to a long photoperiod (LD 14:10) the Bmax values demonstrated a four-fold increase in castrated animals (179 fmoles/mg protein vs. 47 fmoles/mg protein) over intact controls. The relative binding affinity of the major androgens under these conditions remained unchanged, with the exception of AD, where a five-fold increase in the numerical Ki values (decrease in the binding affinity) was recorded (Ki = 9.6 nM).(ABSTRACT TRUNCATED AT 250 WORDS)     

Harderian gland N-acetyltransferase activity in the male Syrian hamster: effects of gonadectomy, short photoperiod exposure, or subcutaneous melatonin implants

The activities of NAT and HIOMT and the melatonin concentration in the Harderian glands of intact, gonadectomized, and gonadally-regressed male Syrian hamsters were studied. To produce gonadal regression, hamsters were exposed to either artificial or naturally short photoperiods. NAT activity of castrated and gonadally-regressed hamsters was always less in comparison to that of animals with intact gonads. Castrated hamsters exposed to long days showed higher NAT activity than that of castrated animals exposed to short photoperiods indicating that light may have some influence on Harderian NAT independent of the gonadal status. Also, gonadally-regressed hamsters exposed to long photoperiods exhibited higher NAT activity in comparison to gonadally-regressed animals exposed to short days. The HIOMT activity and melatonin content of Harderian glands in all these groups of male Syrian hamster were very low.     

Reductions in hamster serum thyroxine levels by melatonin are not altered by changes in serum testosterone

Daily melatonin injections reduce reproductive and thyroid hormones in male Syrian hamsters. The interrelationship between the decline in these hormones is not known. To explore this relationship, male Syrian hamsters were divided into four groups: castrated, implanted with testosterone (5-mm silastic implants), both treatments, or neither treatment. One-half of each group of hamsters (n = 7 or 8) were injected with melatonin (25 mg) daily at 1730 h. The other half of each group received daily vehicle injections. Ten weeks later, the hamsters were anesthetized and decapitated. Testes weights, serum testosterone, and serum thyroxine levels were measured. As expected, testes and serum testosterone levels were uniformly low in all of the melatonin-treated hamsters. All of the melatonin-treated groups also had lower than normal thyroxine values irrespective of gonadal treatment. Interestingly, in the non-melatonin-treated hamsters, serum thyroxine values were decreased in the castrated group and increased in the testosterone-implanted group. These results suggest that castration can reduce serum thyroxine levels in male Syrian hamsters and that replacement of testosterone restores these levels to normal. Notably, the declines in thyroxine levels produced by daily melatonin injections were not restored by testosterone implants in castrated or intact hamsters. Therefore, melatonin-induced reductions in thyroxine are not mediated by concurrent reductions in serum testosterone levels. It appears that melatonin-induced reductions in serum thyroxine levels do not use the same mechanism as castration-induced reductions.     

Melatonin regulates energy balance and attenuates fever in Siberian hamsters

Fever is considered an important host defense response but requires significant metabolic energy. During winter many animals must balance immune function with competing physiological demands (i.e. thermoregulation) to survive. Winterlike patterns of melatonin secretion induce a number of energy-saving adaptations. For instance, Siberian hamsters attenuate the duration of fever during simulated short winter day lengths, presumably to conserve energy. To determine the proximate role of melatonin in mediating this photoperiodic response, hamsters housed in long days were injected with saline or melatonin 4 h before lights off for either 1 or 6 wk and assessed for fever following injections of bacterial lipopolysaccharide. Fever duration was attenuated (32%) only in hamsters that decreased body mass, increased cortisol, and exhibited gonadal regression in response to 6 wk of melatonin. Because melatonin-treated hamsters lost significant body mass, fever was assessed in a second long-day group following ad libitum food intake, food restriction, or 24-h food deprivation. Food restriction sufficient to reduce body mass by approximately 25%, but not to reduce leptin, did not influence fever, and 24-h food deprivation virtually abolished fever. Our data suggest that long-term exposure to long-duration melatonin signals is required to induce the physiological changes necessary for short-day immune responses, perhaps involving interactions with hormones such as cortisol and leptin.