Influences of the paraventricular and suprachiasmatic nuclei and olfactory bulbs on melatonin responses in the golden hamster

Removal of the pineal, or denervation of this gland by superior cervical ganglionectomy, blocks testicular regression in golden hamsters exposed to short photoperiods. Aspiration of the olfactory bulbs or lesions of the suprachiasmatic or paraventricular nuclei of the hypothalamus (SCNx or PVNx) have similar effects. We have examined the effects of these operations on pineal melatonin content and gonadal responses to various patterns of exogenous melatonin in order to examine the roles played by the olfactory bulbs, the SCN, and the PVN in hamster photoperiodism. SCNx and PVNx significantly reduced pineal melatonin content throughout the dark phase, while bulbectomy did not significantly affect melatonin concentrations at the time of the nocturnal peak. Bulbectomy significantly delayed the nightly onset of locomotor activity in hamsters exposed to 14L:10D, but not that of animals housed in 10L:14D. Although bulbectomy reduced the gonadal response to one or three daily injections of melatonin, these individuals exhibited significant testicular regression in response to melatonin as long as injections fell in the evening. In contrast, destruction of the PVN rendered hamsters unresponsive to one daily melatonin injection, but equally responsive to three injections, regardless of the time of day at which these injections were given. Whereas exposure of bulbectomized hamsters to 30 weeks of short days made them refractory to subsequent melatonin challenge, PVNx hamsters remained sensitive to appropriately timed melatonin treatments regardless of their photoperiodic history. Many, but not all hamsters that experienced complete SCN lesions remained sensitive to three daily melatonin injections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circadian regulation of pineal melatonin and reproduction in the Djungarian hamster

Gonadal state, pineal melatonin rhythms, and locomotor activity rhythms were examined in juvenile male Djungarian hamsters exposed to non-24-hr light cycles ("T-cycles") or to full photoperiods. At the end of 1 month, hamsters exposed to a 1-hr pulse of light every 24.33 hr (T 24.33) exhibited small testes, whereas those receiving the same amount of light every 24.78 hr (T 24.78) displayed stimulated gonads, ten-fold larger in size. Accompanying the nonstimulatory effect of the T 24.33 cycle were nocturnal peaks in both pineal melatonin content and serum melatonin concentration which were longer by approximately 4 hr than those observed on the photostimulatory T 24.78 cycle. Exposure to an intermediate-length T-cycle (T 24.53) resulted in a mixed gonadal response and in pineal and serum melatonin peaks of intermediate duration. Wheel-running activity was entrained to the T-cycles such that light was present only near the beginning of the subjective night, its phase (relative to activity onset) differing only slightly among T-cycle groups. Hence the durational differences observed in the melatonin peaks were apparently not due to the acute suppressive or phase-advancing effects of morning light on melatonin biosynthesis, but were rather the result of differences in the endogenous control of pineal activity by the circadian pacemaker system. While no strong correlation was detected between gonadal state and the phase of locomotor activity onset relative to the light pulse, a significant correlation was observed between gonadal state and the duration of daily locomotor activity (alpha). These data were compared to similar measures obtained from hamsters exposed to long-versus short-day full photoperiods (LD 16:8 vs. LD 10:14). In summary, the results of this study indicate involvement of the circadian pacemaker system of Djungarian hamsters in the control of pineal melatonin synthesis and secretion, and in photoperiodic time measurement. Furthermore, these data strengthen the hypothesis that it is the duration of nocturnal pineal melatonin secretion that is the critical feature of this neuroendocrine gland's photoperiodic signal.     

Role of photoperiod and melatonin in seasonal acclimatization of the djungarian hamster,Phodopus sungorus

The Djungarian hamster,Phodopus sungorus, shows a clear annual cycle in some thermogenic parameters such as nonshivering thermogenesis (NST) and cold resistance. These seasonal changes were found to be basically controlled by natural changes in photoperiod. Further support for this view was obtained by exposing the hamsters to artificial long and short photoperiods.Implantation of melatonin during fall and winter results in an increased thermogenic capacity in both short and long day hamsters comparable to that shown by values of control hamsters exposed to short photoperiods during winter. This thermotropic action of melatonin and of short photoperiod could be found only in fall and winter whereas during spring and summer, melatonin, like photoperiod, had no influence on thermogenic capacities. These results show that the actions of melatonin and photoperiod vary with the season and that they depend upon the photoperiodic history of the hamsters. Our results further indicate that the pineal gland with its hormone melatonin is involved in mediation of photoperiodic control of seasonal acclimatization.     

Photoperiodic modulation of sexual and aggressive behavior in female golden hamsters (Mesocricetus auratus): role of the pineal gland

Pinealectomized female hamsters (Mesocricetus auratus) housed in a short-day photoperiod were ovariectomized and tested for hormone-induced sexual receptivity in order to investigate the role of the pineal gland in the control of behavioral sensitivity to exogenous ovarian steroid hormones (Experiment 1). Behavioral sensitivity to hormones was further investigated in females maintained in a long-day photoperiod and rendered acyclic by daily administration of exogenous melatonin (Experiment 2). Female aggressive behavior was also monitored in all tests. Pinealectomy did not affect the reduced behavioral sensitivity to exogenous estrogen (E) induced by short days. These animals were also partially refractory to the effects of E when combined with low doses of progesterone. In addition, although melatonin administration mimicked the effects of short days on estrous cyclicity, the expression of hormone-dependent behaviors in these animals resembled the pattern displayed by control animals kept in long days. Thus, these findings suggest that the pineal gland plays a negligible role in the photoperiodic modulation of hormone-dependent sociosexual behaviors in female hamsters.     

Effect of melatonin implants on gonadal weights and pineal gland fine structure of the golden hamster

Weekly subcutaneous implants of melatonin in a beeswax pellet prevented the testicular regression which normally occurs in hamsters exposed to short photoperiod for 8 weeks. Normal (14L:10D) hamster testes were indistinguishable from the testes of melatonin-treated (1L:23D) hamsters. The exogenous melatonin had varied effects on the fine structure of the golden hamster pineal gland. Pinealocyte nuclear characteristics of melatonin-treated hamsters (smaller average diameter, less polymorphism, and more heterochromatin) as well as apparent reductions in the amounts of hypertrophic SER and lipid moieties seemed to indicate that melatonin caused inhibition of pineal gland activity, and in this respect counteracted the effects of short photoperiod. However, an apparent increase in the number of large mitochondria, membrane whorls and dense-cored secretory vesicles in pinealocytes of melatonin-treated hamsters suggests enhanced pineal gland activity.     

Pineal melatonin rhythms in female Turkish hamsters: effects of photoperiod and hibernation

Daily rhythms of pineal and serum melatonin content were characterized for adult female Turkish hamsters (Mesocricetus brandti) exposed to long days (16L:8D, 22 degrees C) or after transfer to short days (10L:14D, 22 degrees C). The nocturnal peak of pineal melatonin content was found to be approximately 3 b greater in duration on short than on long days. Changes in levels of serum melatonin closely paralleled those of pineal melatonin. Thus, an effect of photoperiod on synthesis and secretion of pineal melatonin was demonstrated. In a separate experiment, female hamsters were induced to hibernate by exposure to a short-day, cold environment (10L:14D, 6 degrees C). During the 4 to 5-mo hibernation season, Turkish hamsters are known to display 4 to 8-day hours of torpor (body temperature = 7-9 degrees C) alternating with 1 to 3-day intervals of euthermia (body temperature = 35-37 degrees C). Little evidence of nocturnal synthesis or secretion of pineal melatonin was detected in females sampled during torpor. However, animals sampled during the first day after arousal from a torpor bout displayed melatonin rhythms no different in phase or amplitude from those seen in females held at 22 degrees C. Thus, despite the absence of pineal melatonin output during torpor, the pineal gland of hibernating Turkish hamsters produces an appropriately phased, rhythmic melatonin signal during intervals of euthermia.     

A melatonin-independent seasonal timer induces neuroendocrine refractoriness to short day lengths.

The duration of nocturnal pineal melatonin secretion transduces effects of day length (DL) on the neuroendocrine axis of photoperiodic rodents. Long DLs support reproduction, and short DLs induce testicular regression, followed several months later by spontaneous recrudescence; gonadal regrowth is thought to reflect development of tissue refractoriness to melatonin. In most photoperiodic species, pinealectomy does not diminish reproductive competence in long DLs. Turkish hamsters (Mesocricetus brandti) deviate from this norm: elimination of melatonin secretion in long-day males by pinealectomy or constant light treatment induces testicular regression and subsequently recrudescence; the time course of these gonadal transitions is similar to that observed in males transferred from long to short DLs. In the present study, long-day Turkish hamsters that underwent testicular regression and recrudescence in constant light subsequently were completely unresponsive to the antigonadal effects of short DLs. Other hamsters that manifested testicular regression and recrudescence in short DLs were unresponsive to the antigonadal effects of pinealectomy or constant light. Long-term suppression of melatonin secretion induces a physiological state in Turkish hamsters similar or identical to the neuroendocrine refractoriness produced by short-day melatonin signals (i.e., neural refractoriness to melatonin develops in the absence of circulating melatonin secretion). A melatonin-independent interval timer, which would remain operative in the absence of melatonin during hibernation, may determine the onset of testicular recrudescence in the spring. In this respect, Turkish hamsters differ from most other photoperiodic rodents.     

Nocturnal increase in the sensitivity of the Syrian hamster pineal gland to isoproterenol is darkness dependent

The sensitivity of the Syrian hamster pineal gland to stimulation by isoproterenol is greatly increased in the latter half of the daily dark phase. This increased sensitivity requires a period of dark exposure for up to 6.5 hr. Also, if dark-maintained hamsters are exposed to light in the latter half of the night pineal melatonin levels drop precipitously but can be restimulated by isoproterenol administration. As the interval of light exposure continues, however, the pineal sensitivity to isoproterenol decreases.     

Development of rhythmic melatonin secretion from the pineal gland of embryonic mummichog (Fundulus heteroclitus)

The pineal gland of vertebrates produces and secretes the hormone melatonin in response to changes in the light-dark cycle, with high production at night and low production during the day. Melatonin is thought to play an important role in synchronizing daily and/or seasonal physiological, behavioral, and developmental rhythms in vertebrates. In this study, the functional development of the pineal melatonin-generating system was examined in the mummichog, Fundulus heteroclitus, an euryhaline teleost. In this species, the pineal gland contains an endogenous oscillator, ultimately responsible for timing the melatonin rhythm. Oocytes from gravid females were collected and fertilized in vitro from sperm collected from mature males. Skull caps containing attached pineal glands were obtained from F. heteroclitus embryos at different embryonic stages and placed in static or perfusion culture under various photoperiodic regimes. Rhythmic melatonin secretion from pineal glands of embryonic F. heteroclitus embryos exposed to a 12L:12D cycle in static culture was observed at five days post-fertilization. The ontogeny of circadian-controlled melatonin production from F. heteroclitus pineal glands exposed to constant darkness for five days was also seen at day five post-fertilization. These data show that early development of the pineal melatonin-generating system in this teleost occurs prior to hatching. Pre-hatching development of the melatonin-generating system may confer some selective advantage in this species in its interactions with the environment.     

Ability of tryptophan derivatives to mimic melatonin's action upon the Syrian hamster reproductive system

The ability of 18 different tryptophan derivatives to induce gonadal regression in Syrian hamsters when injected daily at either midday or late evening has been examined. The compounds chosen have either been identified within mammalian pineal glands or are thought to be possible metabolic derivatives of melatonin. Of the compounds tested, only melatonin and 5-methoxytryptamine were found to possess antigonadotropic activity. 5-Methoxytryptamine's potency, however, was 1/10th that of melatonin and, like melatonin, 5-methoxytryptamine was effective when injected in the evening but not when injected during midday. In addition to the general survey of tryptophan derivatives for antigonadal capability when injected, 5-methoxytryptamine, melatonin, and 5-methoxytryptophol were compared relative to their abilities to prevent photo-induced gonadal regression when administered within beeswax implants. Again 5-methoxytryptamine and melatonin, but not 5-methoxytryptophol, were effective with 5-methoxytryptamine's potency being less than that of melatonin. These results indirectly support the contention that melatonin is the pineal product which mediates photoperiodic effects upon the Syrian hamster reproductive system.     

The circadian system of ruin lizards: a seasonally changing neuroendocrine loop?

Previous studies have shown that the amplitude of daily melatonin production in cultured ruin lizard pineal organs explanted in the summer is significantly higher than that from organs explanted in the winter. To test whether seasonal photoperiodic changes are decoded autonomously by the pineal gland, pineals explanted in summer were cultured in vitro and exposed to changes between winter and summer photoperiods. The changes in photoperiod duration did not affect the daily profiles of in vitro melatonin production. The discrepancy between the present in vitro results and those from lizards exposed to winter or summer photoperiods before pineal explantation supports the view that circadian information entering the pineal gland via its innervation is involved in determining seasonal changes of melatonin production in ruin lizards. We further examined whether a central component of the circadian system of ruin lizards, specifically the retinae of the lateral eyes, expresses similar seasonal changes in function as does the pineal gland. We did not find any difference between summer and autumn-winter in the effectiveness of either bilateral retinalectomy or optic nerve lesion-at the level of the optic chiasm-in altering circadian locomotor behavior in constant conditions. Both surgical procedures mostly induced a shortening of the free-running period of the locomotor rhythm of similar magnitude in all seasons. Thus, the retinae do not appear to participate in the seasonal reorganization of the circadian system in ruin lizards.     

The Circadian System of Ruin Lizards: A Seasonally Changing Neuroendocrine Loop?

Previous studies have shown that the amplitude of daily melatonin production in cultured ruin lizard pineal organs explanted in the summer is significantly higher than that from organs explanted in the winter. To test whether seasonal photoperiodic changes are decoded autonomously by the pineal gland, pineals explanted in summer were cultured in vitro and exposed to changes between winter and summer photoperiods. The changes in photoperiod duration did not affect the daily profiles of in vitro melatonin production. The discrepancy between the present in vitro results and those from lizards exposed to winter or summer photoperiods before pineal explantation supports the view that circadian information entering the pineal gland via its innervation is involved in determining seasonal changes of melatonin production in ruin lizards. We further examined whether a central component of the circadian system of ruin lizards, specifically the retinae of the lateral eyes, expresses similar seasonal changes in function as does the pineal gland. We did not find any difference between summer and autumn‐winter in the effectiveness of either bilateral retinalectomy or optic nerve lesion—at the level of the optic chiasm—in altering circadian locomotor behavior in constant conditions. Both surgical procedures mostly induced a shortening of the free‐running period of the locomotor rhythm of similar magnitude in all seasons. Thus, the retinae do not appear to participate in the seasonal reorganization of the circadian system in ruin lizards.     

Maternal transfer of photoperiodic information in Siberian hamsters. III. Melatonin injections program postnatal reproductive development expressed in constant light

In Siberian hamsters, transference of photoperiodic information from dam to fetus influences pubertal testicular development of the young when reared either in constant light (LL) or postnatal photoperiods of intermediate length (i.e. 14L:10D). The effects of short photoperiods during gestation can be mimicked by administering melatonin to pregnant females. This experiment examined whether there exists a daily pattern of sensitivity to melatonin when it is administered to pineal-intact pregnant females housed on a long photoperiod. Groups of pregnant and lactating females received melatonin at each hour of the day. The young were not treated with exogenous melatonin. At the approximate time of maturation of their endogenous pineal melatonin rhythm (Day 15), the young were placed in LL to suppress pineal melatonin secretion. Young males were killed at 28 days of age. Afternoon (1200 h-2000 h) and late night (0400 h) injections of melatonin into females caused their male young to develop as though gestation occurred on a short photoperiod. Melatonin injections at other times were ineffective. The daily pattern of effectiveness of exogenous melatonin administration to pregnant females resembles that observed in adult males of this and other hamster species and is consistent with the hypothesis that a daily rhythm in sensitivity to melatonin is involved in the transduction of photoperiodic signals.     

Daily rhythm in serum melatonin and leptin levels in the Syrian hamster (Mesocricetus auratus)

Melatonin is produced and secreted by the pineal gland in a rhythmic manner; circulating levels are high at night and low in the day. Leptin is a hormone secreted by adipocytes as a product of the obese gene and plays an important role in regulating body energy homeostasis and reproductive function in rodents and humans. The present study was conducted to examine daily fluctuations in serum levels of melatonin and leptin in Syrian hamster. We measured serum leptin and melatonin levels by ELISA in (a) intact and pinealectomized (pinx) male hamsters kept under long daylight conditions [14 h of light (14L)]; (b) intact and pinx hamsters under short daylight (10L); and (c) intact hamsters in constant light (24L). Blood samples were obtained every 2 h throughout a 24-h period. Statistically significant circadian variations were found in both melatonin and leptin profiles. Their relationship was inverse, i.e. when melatonin was high in the serum, leptin was comparably low. These results suggest that there is a rhythm in leptin levels in the adult male Syrian hamster and this rhythm is pineal gland (melatonin) and/or photoperiod dependent.     

Effects of short-term cold exposure on pineal biosynthetic function in rats

In light of recent studies demonstrating stress-induced changes in pineal indoleamine metabolism, we tested the effect of acute cold stress on pineal biosynthetic function. Adult male rats were subjected to 30, 60, or 120 min of cold exposure (Ta = 2 degrees C) during either the light or dark phase of the daily photoperiodic cycle. Controls were kept at room temperature (22 +/- 2 degrees C). Animals were killed by decapitation and pineals were analyzed by radioimmunoassay for melatonin content and by radioenzymeassay for the activity of N-acetyltransferase (NAT). Cold exposure during the day elicited no significant changes in pineal indoleamine metabolism. Exposure to cold for 1 hr during the second hour after lights off slightly increased pineal melatonin content, without a concomitant change in NAT activity. Rats exposed to 2 hr of cold beginning 2 hr after lights off, however, displayed a 50% reduction in NAT activity, whereas pineal melatonin content remained unchanged. The paradoxical response of pineal NAT activity and melatonin content are not uncommon when rats are exposed to adverse stimuli.     

Hormonal modulation of pineal melatonin synthesis in rats and Syrian hamsters: effects of streptozotocin-induced diabetes and insulin injections

Pineal levels of tryptophan, 5-hydroxytryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and the enzyme activities of N-acetyltransferase and hydroxyindole-O-methyltransferase were determined in male albino rats and Syrian hamsters that were injected with insulin twice daily for three days, or injected with streptozotocin to induce diabetes. Neither insulin injections nor streptozotocin diabetes had any effect on pineal melatonin production in rats. In hamsters, diabetes reduced the nocturnal peak of pineal melatonin content by approximately one half, while insulin injections had no effect on pineal melatonin levels; however, insulin injections did cause a slight increase in pineal N-acetyltransferase activity. These findings indicate that the pineal gland of the hamster may be more sensitive to alterations in plasma insulin levels than the same organ in rats.     

The role of the pineal gland in the photoperiodic control of bird song frequency and repertoire in the house sparrow, Passer domesticus

Temperate zone birds are highly seasonal in many aspects of their physiology. In mammals, but not in birds, the pineal gland is an important component regulating seasonal patterns of primary gonadal functions. Pineal melatonin in birds instead affects seasonal changes in brain song control structures, suggesting the pineal gland regulates seasonal song behavior. The present study tests the hypothesis that the pineal gland transduces photoperiodic information to the control of seasonal song behavior to synchronize this important behavior to the appropriate phenology. House sparrows, Passer domesticus, expressed a rich array of vocalizations ranging from calls to multisyllabic songs and motifs of songs that varied under a regimen of different photoperiodic conditions that were simulated at different times of year. Control (SHAM) birds exhibited increases in song behavior when they were experimentally transferred from short days, simulating winter, to equinoctial and long days, simulating summer, and decreased vocalization when they were transferred back to short days. When maintained in long days for longer periods, the birds became reproductively photorefractory as measured by the yellowing of the birds' bills; however, song behavior persisted in the SHAM birds, suggesting a dissociation of reproduction from the song functions. Pinealectomized (PINX) birds expressed larger, more rapid increases in daily vocal rate and song repertoire size than did the SHAM birds during the long summer days. These increases gradually declined upon the extension of the long days and did not respond to the transfer to short days as was observed in the SHAM birds, suggesting that the pineal gland conveys photoperiodic information to the vocal control system, which in turn regulates song behavior.     

Parameters of the circadian rhythm of pineal melatonin secretion affecting reproductive responses in Siberian hamsters

The major function of the mammalian pineal gland appears to be its central role in photoperiodism. The pineal hormone, melatonin, is synthesized and secreted primarily at night, under the control of a circadian oscillator that is entrained to the light-dark cycle. Both the circadian phase and the duration of the nocturnal peak of melatonin secretion are established primarily by interactions between the endogenous circadian oscillator and the daily photic cycle. The duration of the melatonin peak varies inversely with day length, and this relationship between day length and the duration of each circadian melatonin peak appears to be an integral part of the photoperiodic mechanism. When pinealectomized animals are given daily melatonin infusions of long duration, they exhibit physiologic responses that normally are observed during exposure to short day photoperiods; when administered short-duration melatonin infusions, the animals display long photoperiod-type responses. In addition to the importance of the duration of each melatonin peak, certain other parameters appear to be significant. If a long-duration infusion of melatonin is interrupted by a period of 2 hours or more without melatonin (i.e., to produce two short duration infusions), the responses are those typical for long day-exposed animals. Thus, to elicit short day-type responses, each long-duration melatonin peak must be relatively continuous; responses are not determined simply by the total time of exposure to melatonin in each circadian cycle. Also, long-duration melatonin peaks may not be effective to elicit photoperiod-type responses unless they are present at frequencies of nearly once every 24 hours or more.     

Vitamin A deficiency reduces the responsiveness of pineal gland to light in Japanese quail (Coturnix japonica)

Synthesis of melatonin in pineal gland is under the control of light environment. The recent finding of the presence of rhodopsin-like photopigment (pinopsin) and retinal in the avian pinealocytes has led to a hypothesis that vitamin A is involved in photoresponses of the pineal gland. We have thus analyzed the effect of vitamin A deficiency on the regulatory system of melatonin synthesis in the pineal gland of Japanese quail. Depletion of vitamin A from Japanese quails was attained by feeding them with a vitamin A-free diet supplemented with retinoic acid. In the vitamin A-deficient birds, diurnal rhythm in melatonin production persisted such that the phase of the wave was similar to that seen in the control birds. However, the amplitude of the nighttime surge of pineal melatonin was damped by vitamin A deficiency. When the control birds were briefly exposed to light at night, pineal melatonin dropped to the daytime level. In contrast, only slight decrease was observed in the vitamin A-deficient quails. The light responsiveness was restored after feeding the vitamin A-deficient quails with the control diet for 1 week. These results indicate that vitamin A plays essential roles in maintaining sufficient responsiveness of the avian pineal gland to photic input.     

Role of the pineal and its hormone melatonin in the termination of photorefractoriness in golden hamsters

Continuous exposure of male hamsters to short day lengths induces testicular regression. This is followed many weeks later by spontaneous recrudescence of the testes with reinitiation of spermatogenesis and function of the accessory sexual glands. Hamsters at this stage of the annual reproductive cycle are refractory to short photoperiods--even continuous darkness will not induce another bout of testicular regression. Animals refractory to short days are also refractory to the pineal hormone melatonin and a number of investigators attribute spontaneous recrudescence and photo and melatonin refractoriness to a developed target cell insensitivity to endogenous melatonin from the pineal. Refractoriness is terminated by exposure to long days for at least 11 weeks. The pineal gland is reported to be essential for this process. We report here the effects of pinealectomy, daily melatonin injections, and constant-release melatonin implants on the ability of male hamsters to recover from the refractory state. In the absence of the pineal gland, refractory male hamsters did not discriminate (count?) 15 weeks of long days to terminate refractoriness. Daily melatonin injections at 1900 h, but not at 1200 h (lights 0600-2000 h) during the 15 weeks of long-day exposure blocked the recovery from refractoriness. Constant-release melatonin implants abolished the animals ability to measure 12 and 15 weeks of long days to terminate refractoriness. These results demonstrate that general target tissue insensitivity to melatonin cannot account for the refractory state in hamsters, that a multiplicity of target tissues may exist for melatonin to account for its varied roles throughout the annual reproductive cycle in hamsters, and that the pineal gland is intimately involved in the animals' ability to measure a prescribed duration of long days to terminate refractoriness.