Exposure to long summer days affects the human melatonin and cortisol rhythms

Exposure of 8 human subjects in summer to a natural 16 h bright light photoperiod phase advanced the morning salivary melatonin decline and cortisol rise and shortened the nocturnal melatonin signal by 2 h relative to the winter patterns of the same subjects followed under a combined artificial and natural light 16 h photoperiod. The data suggest that summer days experienced from sunrise till sunset and not winter days with a combined artificial and natural light long photoperiod evoke a true long day response of the human circadian system.     

Short-day stimulation of testicular activity and immunoreactivity of the hypothalamic GnRH system in mink following deafferentation of the pineal body by bilateral superior cervical ganglionectomy and melatonin replacement.

The effects of superior cervical ganglionectomy on testicular function (testis volume and plasma testosterone levels) and the immunocytochemical activity of the GnRH hypothalamic system were studied in the mink, a short-day breeder. Animals reared in a natural photoperiod were (i) ganglionectomized at four different times during the period extending from the end of summer to the end of autumn (September 15, October 20, October 28, and December 1), and (ii) reared for 50 days in a short gonadostimulatory photoperiod (4L:20D). Lastly, an attempt was made to overcome the effects of superior cervical ganglion removal by administering melatonin to mink reared in a natural photoperiod. In mink reared in a natural photoperiod, deafferentation of the pineal on September 15 (L = 12.5 h) or October 20 (L = 10.5 h) resulted in consistently low values of testicular volume and plasma testosterone until the end of the experiment (February). When the operation was performed on October 28 (L = 10 h) testicular activity was initiated but only lasted a short time and did not allow maximal gonadal development. When superior cervical ganglionectomy was carried out on December 1 (L = 8.5 h), during the phase of renewed testicular activity, the increases in testicular volume and testosterone levels were not affected by the operation and the subsequent variation of these parameters was identical to that observed in intact animals. Similarly, in mink reared for 50 days in a photoperiod of 4L:20D before superior cervical ganglionectomy, deafferentation of the pineal did not prevent gonadostimulation induced by short days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Triggering of neuroendocrine refractoriness to short-day patterns of melatonin in Siberian hamsters

Short day lengths induce gonadal regression within 6 weeks in Siberian hamsters, but this inhibitory effect eventually wanes and reproductive competence is regained after 4-6 months in short days. These experiments were undertaken to determine whether continuous exposure to short days for several months is necessary to induce neuroendocrine refractoriness, or if a few weeks of short days are sufficient to trigger processes that culminate in refractoriness several months later. Adult male Siberian hamsters transferred from their natal long-day photoperiod of 15L (15 h light/day) to a short-day photoperiod of 10L were pinealectomized (PINx) after 0, 6, 12, 21 or 40 weeks of exposure to 10L. Intact hamsters kept in 10L manifested gonadal regression by week 6 and completed gonadal recrudescence by week 40, at which time they too were PINx. Beginning at week 40 all hamsters were infused s.c. with melatonin for 10 h/day for 6 consecutive weeks. This treatment induces gonadal regression in photosensitive hamsters. At the end of melatonin treatment, maximal gonadal regression was recorded for hamsters PINx at week 0 and those PINx after 40 weeks in long days. Hamsters PINx after 40 week of short day treatment were completely unresponsive to melatonin whereas those PINx after 6 and 12 weeks had intermediate responses. The percentage of hamsters whose reproductive apparatus was refractory to melatonin at week 40 increased with increasing duration of exposure to short days prior to PINx. Refractoriness was induced by relatively few weeks of short days in some hamsters, whereas others required much more extensive exposure. Induction of refractoriness is triggered by a fraction of the short days that hamsters experience in nature but may not be manifested until many weeks later when it coincides with gonadal recrudescence. In nature all hamsters are exposed to short days for at least 25 weeks, ensuring refractoriness in most individuals.     

Daily and seasonal variations in the concentration of melatonin in the human pineal gland

To elucidate whether pineal melatonin secretion is affected by changes in day length, we determined the concentration of melatonin in human pineal glands obtained at autopsy from 66 male subjects, aged 16–84 years over a period of 12 consecutive months. Based on the time of death, a day–night difference in pineal melatonin levels was evident only in the long photoperiod (April–September) with significantly higher melatonin concentrations occurring at night (2200–1000 h). Nighttime values in the long photoperiod were significantly higher than the nighttime values during the short photoperiod (October–March). During the short photoperiod, the data suggested a possible phase-delay in melatonin secretion. Day–night difference was evident in young subjects (30–60 years), but not in elderly subjects (61–84 years). Elderly subjects had lower total melatonin levels (day and night values) although statistically not significant. Therefore, melatonin levels did not decline with age and when the data were analyzed by age there was no significant day–night difference in melatonin levels. These data indicate that the concentration of melatonin in the human pineal is augmented only during the long photoperiod. The results suggest a partial effect of photoperiod on melatonin secretion in humans. This may result from living in an artificial light environment or due to other nonphotic signals involved in generating melatonin rhythm.     

The circadian rhythm of Per1 gene product in the rat suprachiasmatic nucleus and its modulation by seasonal changes in daylength

The suprachiasmatic nucleus (SCN) of rats maintained under a 12-h light, 12-h dark cycle (LD12:12) as well as of those released into darkness exhibited the rhythm of a clock gene Per1 product, PER1 protein, with the maximum late in the subjective day and early night and minimum in the morning. The rhythm was phase delayed by 6-8 h compared with the reported rhythm of Per1 mRNA in the rat SCN [L. Yan et al. Neuroscience 94 (1999) 141]. Under a long, LD16:8, artificial photoperiod, the interval of elevated PER1-immunoreactivity was at least 4 h longer than that under a short, LD 8:16 photoperiod, due mainly to an earlier PER1 day-time rise under the long photoperiod. Under a natural photoperiod, profiles of the PER1 rhythm in summer and in winter resembled those under corresponding artificial photoperiods; therefore, twilight did not affect the rhythm in a substantial way. Under all photoperiods, when PER1 immunoreactivity was elevated, immunopositive cells were localized in the dorsomedial rather than in the ventrolateral part of the SCN. As the Per1 gene is a part of a molecular clockwork and as the rhythm of its product is modulated by the photoperiod, it appears that the whole molecular clockwork in the rat SCN is photoperiod-dependent and thus shaped by the season of the year.     

The Effect of Photoperiod on Plasma Levels of Melanin-Concentrating Hormone in the Trout

The neurohypophysial melanin-concentrating hormone, MCH, plays a role in adaptive colour change in teleost fishes, inducing pallor when the fish is placed in pale-coloured surroundings. The present study shows that its plasma concentration, measured in groups of white-adapted fish, is not uniformly high throughout the day but follows a clear diurnal pattern. Over a 24 h cycle, plasma concentrations rise gradually during the morning to reach peak values around the middle of the photophase, after which they decline significantly before night. Lowest concentrations are observed during the dark period. This pattern was observed under a long photoperiod in summer and a short photoperiod in winter. The peak was shifted within a week of changing the onset of either light or dark. When dawn was delayed by 6 h for fish held on a long photoperiod, the usual morning rise in hormone titres was suppressed but, with the advent of light, hormone concentrations rose more rapidly than usual to reach peak values at about the normal time. If the dawn was advanced by 6 h for fish held under short photoperiod conditions, then peak concentrations were attained 6 h precociously. Fish from a long photoperiod placed in constant light showed a pattern of MCH release which approximated to the normal over the first 24 h period but plasma values then became raised and periodicity was no longer discernible. Plasma hormone concentrations were much reduced in trout kept in black coloured tanks in which nocturnal and daytime values differed, but significant differences during the photophase were not demonstrable. The results suggest that an illuminated white background can initiate the early morning release of MCH, and that an endogenous pacemaker underlies the pattern of MCH secretion.     

Evidence for RGS4 modulation of melatonin and thyrotrophin signalling pathways in the pars tuberalis

In mammals, the pineal hormone melatonin is secreted nocturnally and acts in the pars tuberalis (PT) of the anterior pituitary to control seasonal neuroendocrine function. Melatonin signals through the type 1 Gi-protein coupled melatonin receptor (MT1), inhibiting adenylate cyclase (AC) activity and thereby reducing intracellular concentrations of the second messenger, cAMP. Because melatonin action ceases by the end of the night, this allows a daily rise in cAMP levels, which plays a key part in the photoperiodic response mechanism in the PT. In addition, melatonin receptor desensitisation and sensitisation of AC by melatonin itself appear to fine-tune this process. Opposing the actions of melatonin, thyroid-stimulating hormone (TSH), produced by PT cells, signals through its cognate Gs-protein coupled receptor (TSH-R), leading to increased cAMP production. This effect may contribute to increased TSH production by the PT during spring and summer, and is of considerable interest because TSH plays a pivotal role in seasonal neuroendocrine function. Because cAMP stands at the crossroads between melatonin and TSH signalling pathways, any protein modulating cAMP production has the potential to impact on photoperiodic readout. In the present study, we show that the regulator of G-protein signalling RGS4 is a melatonin-responsive gene, whose expression in the PT increases some 2.5-fold after melatonin treatment. Correspondingly, RGS4 expression is acutely sensitive to changing day length. In sheep acclimated to short days (SP, 8 h light/day), RGS4 expression increases sharply following dark onset, peaking in the middle of the night before declining to basal levels by dawn. Extending the day length to 16 h (LP) by an acute 8-h delay in lights off causes a corresponding delay in the evening rise of RGS4 expression, and the return to basal levels is delayed some 4 h into the next morning. To test the hypothesis that RGS4 expression modulates interactions between melatonin- and TSH-dependent cAMP signalling pathways, we used transient transfections of MT1, TSH-R and RGS4 in COS7 cells along with a cAMP-response element luciferase reporter (CRE-luc). RGS4 attenuated MT1-mediated inhibition of TSH-stimulated CRE-luc activation. We propose that RGS4 contributes to photoperiodic sensitivity in the morning induction of cAMP-dependent gene expression in the PT.     

Melatonin directly resets the rat suprachiasmatic circadian clock in vitro.

The environmental photoperiod regulates the synthesis of melatonin by the pineal gland, which in turn induces daily and seasonal adjustments in behavioral and physiological state. The mechanisms by which melatonin mediates these effects are not known, but accumulating data suggest that melatonin modulates a circadian biological clock, either directly or indirectly via neural inputs. The hypothesis that melatonin acts directly at the level of the suprachiasmatic nucleus (SCN), a central mammalian circadian pacemaker, was tested in a rat brain slice preparation maintained in vitro for 2-3 days. Exposure of the SCN to melatonin for 1 h late in the subjective day or early subjective night induced a significant advance in the SCN electrical activity rhythm; at other times melatonin was without apparent effect. These results demonstrate that melatonin can directly reset this circadian clock during the period surrounding the day-night transition.     

A melatonin agonist and N-acetyl-N2-formyl-5-methoxykynurenamine accelerate the reentrainment of the melatonin rhythm following a phase advance of the light-dark cycle

The rate of entrainment of the urinary 6-sulphatoxymelatonin rhythm to a phase-advanced photoperiod and the influence of a melatonin agonist and melatonin analogues and metabolites on the entrainment were investigated in male rats. Following an 8-h advance of a 14:10 light-dark photoperiod, the 6-sulphatoxymelatonin rhythm was disrupted completely for two days and became entrained after 5-6 days. Subcutaneous injection of the melatonin agonist, 6-chloromelatonin (0.5 mg/kg) and the brain metabolite, N-acetyl-N2-formyl-5-methoxykynurenamine (aFoMK, 10 mg/kg) two hours after dark onset on the day after the phase advance accelerated the entrainment to the new photoperiod. N-acetyl-5-methoxykynurenamine, 6-chloro-2,3-dihydromelatonin, 1,3-dihydro-5-(ethylacetamide)-7-methoxy-2H-1,4-benzodiazepin++ +-2-one and N-formylkynurenine were all without effect at a dose of 10 mg/kg. Treatment of rats with aFoMK on the day of the phase advance (day 0) together with treatment on day +1 accelerated the entrainment to the photoperiod whereas a single injection on day +2 or injections on day +1 and day +2 were without effect at a dose of 10 mg/kg. These results: (a) demonstrate the usefulness of monitoring urinary 6-sulphatoxymelatonin rhythms for pineal studies; (b) show that melatonin can indirectly influence its own secretion, presumably by interactions with the suprachiasmatic nucleus; and (c) provide further evidence for the biological activity of the brain metabolite of melatonin, N-acetyl-N2-formyl-5-methoxykynurenamine.     

Frequency coding of melatonin signals sufficient to induce testicular growth in photoregressed Siberian hamsters

Integration of melatonin signals over the course of several weeks was studied in male Siberian hamsters maintained in a short day length (10 h light/day) from birth (d 0). On d 35, hamsters with undeveloped testes were housed in constant light and received 5 h s.c. infusions of melatonin (MEL; 100 ng/infusion) or saline (SAL) over the next 30 days. Infusions were provided either every day (30 MEL), every other day (1 MEL/1 OFF), for 2 consecutive days followed by 2 days with no infusion (2 MEL/2 OFF), for 5 consecutive days followed by 5 days with no infusion (5 MEL/5 OFF), for 15 consecutive days followed by 15 days with no infusion (15 MEL/15 OFF), or saline every day (30 SAL). On d 65 testes weights of 30 MEL hamsters were greater than those from 30 SAL, 1 MEL/1 OFF, or 2 MEL/2 OFF groups, but did not differ significantly from those of 5 MEL/5 OFF and 15 MEL/15 OFF animals. Serum FSH concentrations of 30 MEL hamsters exceeded those of all other groups which did not differ among each other. Between 15 and 30 consecutive daily melatonin signals are necessary and sufficient to initiate and sustain maximal gonadotropic activity in juvenile male hamsters kept in constant light. The neuroendocrine system responsive to melatonin does not bridge intervals of more than a day in any of several combinations and apparently is frequency-coded for maximal responsiveness to daily signals.     

Urinary 6-sulphatoxymelatonin excretory rhythms in laboratory rats: effects of photoperiod and light

The excretion rhythm of the melatonin metabolite, 6-sulphatoxymelatonin, was determined in rats maintained on contrasting14h L: 10h D and10h L: 14h D photoperiods. The novel use of a high protein liquid diet together with an automatic urine collection system facilitated the monitoring of the onset, offset and total production of metabolite before, during and after a 57.5% reduction in the dark period (5.75 h and 8 h delay in lights off). In14L: 10D, melatonin metabolite excretion increased2.7±0.2h after lights off, whereas in10L: 14D, the onset occurred5.1±0.2h after lights off. Duration of melatonin metabolite excretion was not different between the two photoperiods. Reduction of the dark period by 57.5% delayed the appearance of melatonin metabolite excretion until2.15±0.4h and2.9±0.4h after darkness in both long and short photoperiods. Upon restoration of the original photoperiod on the third day, the onset of metabolite excretion was significantly delayed by1.4±0.4h(P < 0.05) in long day animals and2.2±0.2h(P < 0.05) in short day-length compared to the forst day. This study highlights the utility of urinary 6-sulphatoxymelatonin determinations in rats and provides new information on the acute effects of extended evening light on pineal melatonin secretion.     

Disruption of Reproductive Rhythms and Patterns of Melatonin and Prolactin Secretion Following Bilateral Lesions of the Suprachiasmatic Nuclei in the Ewe

To determine whether the photoperiodic responses of reproductive and prolactin (PRL) rhythms in the ewe requires an intact suprachiasmatic nucleus (SCN) driving the pineal rhythm of melatonin secretion, four groups of ovary-intact ewes over a 6-year period were subjected to bilateral (n = 40) or sham lesions (n = 15) of the SCN. Animals were exposed to an alternating 90–120 day photoregimen of 9L:15D and 16L: 8D photoperiods. Blood samples taken twice weekly were assayed for prolactin and for progesterone to monitor oestrous cycles. On several occasions blood samples also were taken at hourly intervals for 24 h and analyzed for melatonin. Melatonin concentrations in sham lesioned ewes were basal during the lights-on period and rose robustly during darkness. Those sheep bearing unilateral lesions of the SCN (n = 13) or where the lesion spared the SCN entirely (n = 8) had patterns of melatonin secretion similar to sham ewes. The remaining ewes, having complete (n = 9) or incomplete bilateral (n = 8) destruction of the SCN, with one exception, had disrupted patterns of melatonin secretion. The nature of this disruption varied from complete suppression to continuously elevated levels. In lesioned ewes where melatonin secretion was not affected the onset and cessation of ovarian cycles were similar to sham ewes; stimulation of oestrous cycles under 9L:15D and cessation of oestrous cycles under 16L:8D. In contrast, 13 of 17 ewes with disrupted melatonin secretion also exhibited disrupted patterns of ovarian activity. In these animals oestrous cycles were no longer entrained by photoperiod but still occurred in distinct clusters, that is, groups of cycles began and ended spontaneously. Sheep with normal melatonin patterns showed low levels of PRL secretion during short days and elevated PRL levels during long days. However, 8 of 13 ewes with disrupted melatonin showed patterns of PRL secretion that were no longer entrained by photoperiod. A minority of ewes with disrupted melatonin patterns still showed reproductive (n = 4) and PRL (n = 5) responses similar to those of sham-lesioned ewes. These results show that bilateral destruction of the SCN in the ewe disrupts the circadian pattern of melatonin secretion and that this disruption usually, but not always, is associated with altered photoperiodic responses. These results strongly suggest that the SCN are important neural elements within the photoperiod time–keeping system in this species. A role for the SCN in the generation of endogenous transitions in reproductive activity (refractoriness) and prolactin secretion is not supported.     

Circadian rhythms of melatonin of patients with severe traumatic brain injury

The study was performed on a group of 5 patients with severe traumatic brain injury and in 2 healthy volunteers as the controls. The examination began 2-5 days after injury. The management of the patients and controls did not affect the natural melatonin circadian rhythm. The first result obtained was the characteristic nocturnal increase of the melatonin level in the healthy subjects. In a group of 5 patients with the severe traumatic brain injury the differences between the day and night time were insignificant. The results of the present study indicate that the severe brain injury gives rise to serious disturbances of the melatonin secretion in the acute posttraumatic period. These disturbances are characterized by the absence of the natural melatonin circadian rhythm. Despite the small number of patients, the obtained results justify further studies.     

Effects of Photoperiod on Kisspeptin Neuronal Populations of the Ewe Diencephalon in Connection with Reproductive Function

Kisspeptin (Kiss) is a key regulator of reproductive function in both prepubertal and adult mammals. Its expression appears to vary throughout the year in seasonal species. We aimed to determine the impact of a change of photoperiod on the size of Kiss neuronal populations found in the preoptic area (POA) and arcuate nucleus (ARC) of the ewe brain. Using immunocytochemistry, we first examined the proportion of neurones expressing Kiss, using HuC/D as a neuronal marker, at different time-points after transition from long days (LD; 16 : 8 h light/dark cycle) to short days (SD; 8 : 16 h light/dark cycle). Luteinising hormone (LH) secretion was measured in ovariectomised oestradiol replaced ewes from the month preceding the transition to SD until the sacrifice of the animals at days 0, 45 and 112 from this photoperiodic transition. High LH levels were only observed in animals killed at day 112. The number of Kiss neurones/mm² doubled in the caudal ARC at day 112. The percentage of neurones showing Kiss immunoreactivity increased significantly in both the POA and ARC in the day 112 group. In a second experiment, ewes kept in LD received an i.c.v. injection of colchicine 20 h before sacrifice. Colchicine treatment increased the number and the percentage of neurones with Kiss in both the POA and caudal ARC. The data obtained suggest that the increase in Kiss neurones detected in the POA and caudal ARC after transition to SD stemmed from an increase in Kiss synthesis. This up-regulation of Kiss content under the shorter day condition appears to be a late event within the cascade activated by a longer secretion of melatonin, which is a critical factor in switching gonadotrophin-releasing hormone secretion to a breeding season profile.     

Potential animal models of seasonal affective disorder

Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions.     

Testicular and somatic growth in Siberian hamsters depend on the melatonin-free interval between twice daily melatonin signals

In Siberian hamsters, day length is encoded by the duration of the nocturnal melatonin signal; short and long melatonin signals over the course of several weeks stimulate and inhibit somatic and gonadal development, respectively, in prepubertal males. We sought to determine whether juvenile male Siberian hamsters respond to multiple melatonin signals each day and the manner in which the sequence of melatonin signals and the duration of the melatonin-free interval between signals affects development. Twenty-one day old male Siberian hamsters, gestated and maintained in a short-day photoperiod of 10 h light/day (10 L), were transferred to constant light to suppress endogenous melatonin secretion and received s.c. infusions of melatonin or saline for 12 days. Hamsters infused with saline retained small testes, whereas one short melatonin infusion each day resulted in significant testicular growth. Other hamsters were provided with two melatonin signals each day, one long (9 h) and one short (4 or 5 h); the order in which these signals was administered and the duration of the melatonin-free interval after each signal varied between groups. In asymmetrical melatonin infusions, the first and second daily infusions were followed by 3-h and 7-h melatonin-free intervals, respectively, whereas in symmetrical infusions, each melatonin signal was followed by a 5-h melatonin-free interval. In the asymmetrical sequence, the melatonin signal that immediately preceded the longer melatonin-free interval determined the rate gonadal growth. Equal melatonin-free intervals after each of the long and short daily melatonin infusions produced intermediate increases in gonadal and somatic development. The hypothalamic-pituitary-gonadal axis of Siberian hamsters can respond to multiple melatonin signals each day, with the rate of testicular growth determined primarily by the duration of the melatonin-free interval following each infusion.     

Gonadotropin responses to naloxone may depend upon spontaneous activity in noradrenergic neurons at the time of treatment

The opiate system is thought to modulate gonadotropin secretion by its effect on catecholamine secretion. This action may be produced by opiates regulating the amount of catecholamine released from presynaptic terminals at a given frequency of depolarization and/or by increasing the rate of impulse traffic within catecholamine neurons. We examined the effects of naloxone, an opiate receptor antagonist, on luteinizing hormone (LH) and prolactin (Prl) secretion in 3 sex steroid-treated, gonadectomized rat models in which we have considerable information on the rates of turnover of norepinephrine (NE) and dopamine (DA) in the hypothalamus. In 7 day ovariectomized rats treated for 2 days with estradiol (E2), the injection of naloxone (10 mg/kg) at 09.15 h produced a small 3-fold rise in LH and a short-lived decline in Prl. In contrast, naloxone, given at 12.15 h, markedly amplified (10-fold) and advanced the time of the LH surge but did not affect afternoon Prl surges. Hypothalamic NE turnovers are low in the morning and high in the afternoon for such animals. Other ovariectomized (OVX) rats received E2 for 2 days and progesterone (P4) on day 2. Such treatment extinguishes the LH surges which normally occur the next day (day 3) but does not affect phasic Prl secretion. Naloxone, given at 09.15 h to E2P4-treated rats on day 3, did not affect basal LH levels but serum Prl declined for about 1 h. When given at 12.15 h, naloxone produced a small 3-fold rise in LH but did not affect phasic Prl release.(ABSTRACT TRUNCATED AT 250 WORDS)     

Seasonal variations of clock gene expression in the suprachiasmatic nuclei and pars tuberalis of the European hamster (Cricetus cricetus)

In mammals, day length (photoperiod) is read and encoded in the main circadian clock, the suprachiasmatic nuclei (SCN). In turn, the SCN control the seasonal rhythmicity of various physiological processes, in particular the secretion pattern of the pineal hormone melatonin. This hormone then operates as an essential mediator for the control of seasonal physiological functions on some tissues, especially the pars tuberalis (PT). In the European hamster, both hormonal (melatonin) and behavioral (locomotor activity) rhythms are strongly affected by season, making this species an interesting model to investigate the impact of the seasonal variations of the environment. The direct (on SCN) and indirect (via melatonin on PT) effect of natural short and long photoperiod was investigated on the daily expression of clock genes, these being expressed in both tissues. In the SCN, photoperiod altered the expression of all clock genes studied. In short photoperiod, whereas Clock mRNA levels were reduced, Bmal1 expression became arrhythmic, probably resulting in the observed dramatic reduction in the rhythm of Avp expression. In the PT, Per1 and Rev-erbalpha expressions were anchored to dawn in both photoperiods. The daily profiles of Cry1 mRNA were not concordant with the daily variations in plasma melatonin although we confirmed that Cry1 expression is regulated by an acute melatonin injection in the hamster PT. The putative role of such seasonal-dependent changes in clock gene expression on the control of seasonal functions is discussed.