Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths.

The dorsomedial nucleus (DMN) of the hypothalamus has been implicated in seasonal control of reproduction. Syrian hamsters with DMN lesions, unlike control hamsters, do not undergo testicular regression after transfer from a long day length (14 h of light per day; LD) to a short day length (8 h of light per day; SD). SDs also markedly reduce hamster locomotor activity (LMA). To assess whether the DMN is a component of the neural circuitry that mediates seasonal variation in LMA, neurologically intact males (controls) and hamsters that had sustained lesions of the DMN (DMNx) were housed in an LD or SD photoperiod for 26 weeks. DMNx that prevented testicular regression counteracted decreases in LMA during 8 to10 weeks of SD treatment; steroid-independent effects of SDs did not override high levels of LMA in DMNx males. As in previous studies, testosterone (T) restoration increased LMA in LD but not SD castrated control males. In the present study, T also failed to increase LMA in SD-DMNx hamsters. The DMN is not necessary to maintain decreased responsiveness of locomotor activity systems to T in SDs, which presumably is mediated by other central nervous system androgen target tissues. Finally, DMNx did not interfere with the spontaneous increase in LMA exhibited by photorefractory hamsters after 26 weeks of SD treatment. We propose that DMN is an essential part of the substrate that mediates seasonal decreases in LMA as day length decreases but is not required to sustain decreased SD responsiveness to T or for development of refractoriness to SDs.

Effects of Pinealectomy and Short Day Lengths on Reproduction and Neuronal RFRP-3, Kisspeptin, and GnRH in Female Turkish Hamsters.

Long days (LDs) stimulate and short days (SDs) inhibit reproduction in photoperiodic rodents by modifying nocturnal pineal melatonin secretion. In LD Turkish hamsters, unlike other rodents, pinealectomy induces reproductive quiescence comparable to that produced by SDs. We assessed whether SDs and pinealectomy induce similar or different patterns of kisspeptin and gonadotropin-inhibitory hormone (also known as RFamide-related peptide-3 [RFRP-3] in mammals) expression, important mediators of seasonal reproductive changes in other species. Brains were harvested from sham-operated female Turkish hamsters maintained in LDs and SDs and LD-pinealectomized (pinx) females, all housed in their respective photoperiods for 12 weeks. Uterine weights were substantially higher in LD-sham than in LD-pinx and SD-sham females. RFRP-3-immunoreactive(-ir) cells in the dorsomedial hypothalamic nucleus were greater in number and size in the reproductively competent LD-sham hamsters than in both reproductively suppressed SD-sham and LD-pinx hamsters. LD-sham hamsters had more kisspeptin-ir cells in the anteroventral periventricular nucleus than did LD-pinx hamsters. Reproductive quiescence, whether induced by short-day lengths or pinealectomy, was generally accompanied by comparable changes in RFRP-3 and kisspeptin, suggesting that long-duration melatonin signaling and withdrawal of melatonin by pinealectomy may act through the same neural substrates to induce gonadal quiescence.

Dorsomedial hypothalamic lesions block Syrian hamster testicular regression in short day lengths without diminishing increased testosterone negative-feedback sensitivity.

The dorsomedial nucleus (DMN) of the hypothalamus, the only site within the mediobasal hypothalamus of Syrian hamsters that both binds melatonin and has abundant concentrations of androgen receptors, has been proposed as a target tissue for induction of seasonal changes in brain sensitivity to steroid negative feedback. We tested whether DMN ablation, which does not interfere with pineal gland secretion of melatonin in short day lengths, prevents testicular regression by altering sensitivity to steroid negative feedback. Hamsters with DMN lesions, unlike control hamsters, failed to undergo testicular regression after transfer from a long (14 h light/day) to a short day length (8 h light/day); however, increased negative-feedback inhibition of follicle-stimulating hormone by testosterone was not compromised by ablation of the DMN, indicating that this tissue is not an essential mediator of seasonal changes in feedback sensitivity. We propose a redundant neural network comprised of multiple structures, each of which contributes to neuroendocrine mechanisms, that determines the effect of short days on gonadal function.

Winter day lengths counteract stimulatory effects of apomorphine and yohimbine on sexual behavior of male Syrian hamsters.

Yohimbine and apomorphine selectively act on noradrenergic and dopaminergic neural substrates to augment male sexual behavior (MSB) in several rodent species. The present study assessed whether these drugs can overcome the suppressive effects of short winter-like day lengths on MSB. Yohimbine treatments that markedly increase copulatory behavior of male hamsters in long days were completely ineffective in facilitating MSB when injected after gonadal regression induced by 16 wks of short day lengths and after complete gonadal recrudescence after 32 wks of short days; apomorphine was similarly ineffective. The brain circuit that mediates MSB either may be less responsive to yohimbine and apomorphine in short than long days, or these drugs may not produce equivalent neurotransmitter changes in the two day lengths. After 32 wks of short-day treatment, all males had undergone testicular recrudescence and successfully ejaculated on initial tests with sexually receptive females after a hiatus of at least 4 mo during which they were denied mating opportunities. This suggests that overwintering males in the field are in a state of reproductive readiness at the outset of spring conditions favorable for survival of offspring.

Elimination of short-day melatonin signaling accelerates gonadal recrudescence but does not break refractoriness in male Turkish hamsters.

Long days stimulate and short days (SDs) inhibit the reproductive axis of photoperiodic rodents. In long-day Turkish hamsters, unlike most other rodents, elimination of pineal melatonin secretion by constant light or pinealectomy initiates a cycle of gonadal involution and recrudescence outwardly similar to that induced by short days. The present study assessed whether short days and constant light induce the seasonal reproductive cycle via common or different interval timing mechanisms. Male hamsters that had undergone gonadal involution in SDs for 8 or 14 weeks were treated with LL for 14 and 8 weeks, respectively. If SDs and LL act via independent mechanisms, then gonadal quiescence of SD-regressed males, which normally lasts 10 weeks, might be extended by LL treatment; alternatively, if SDs and LL act on the same timer, or the timer cannot be retriggered, then LL will not extend the duration of reproductive quiescence. Neither of these outcomes materialized. Instead, male hamsters exposed to LL while reproductively quiescent exhibited accelerated gonadal recrudescence. Extended LL treatment did not restore responsiveness to SDs in photorefractory hamsters. In Turkish hamsters, photoperiodic history determines whether constant light inhibits or stimulates the hypothalamic-pituitary-testicular axis.

Circadian control of kisspeptin and a gated GnRH response mediate the preovulatory luteinizing hormone surge.

In spontaneously ovulating rodents, the preovulatory LH surge is initiated on the day of proestrus by a timed, stimulatory signal originating from the circadian clock in the suprachiasmatic nucleus (SCN). The present studies explored whether kisspeptin is part of the essential neural circuit linking the SCN to the GnRH system to stimulate ovulation in Syrian hamsters (Mesocricetus auratus). Kisspeptin neurons exhibit an estrogen-dependent, daily pattern of cellular activity consistent with a role in the circadian control of the LH surge. The SCN targets kisspeptin neurons via vasopressinergic (AVP), but not vasoactive intestinal polypeptide-ergic, projections. Because AVP administration can only stimulate the LH surge during a restricted time of day, we examined the possibility that the response to AVP is gated at the level of kisspeptin and/or GnRH neurons. Kisspeptin and GnRH activation were assessed after the administration of AVP during the morning (when AVP is incapable of initiating the LH surge) and the afternoon (when AVP injections stimulate the LH surge). Kisspeptin, but not GnRH, cellular activity was up-regulated after morning injections of AVP, suggesting that time-dependent sensitivity to SCN signaling is gated within GnRH but not kisspeptin neurons. In support of this possibility, we found that the GnRH system exhibits pronounced daily changes in sensitivity to kisspeptin stimulation, with maximal sensitivity in the afternoon. Together these studies reveal a novel mechanism of ovulatory control with interactions among the circadian system, kisspeptin signaling, and a GnRH gating mechanism of control.