Kisspeptin Mediates the Photoperiodic Control of Reproduction in Hamsters

Abstract

The KiSS-1 gene encodes kisspeptin, the endogenous ligand of the G-protein-coupled receptor GPR54. Recent data indicate that the KiSS-1/GPR54 system is critical for the regulation of reproduction and is required for puberty onset. In seasonal breeders, reproduction is tightly controlled by photoperiod (i.e., day length). The Syrian hamster is a seasonal model in which reproductive activity is promoted by long summer days (LD) and inhibited by short winter days (SD). Using in situ hybridization and immunohistochemistry, we show that KiSS-1 is expressed in the arcuate nucleus of LD hamsters. Importantly, the KiSS-1 mRNA level was lower in SD animals but not in SD-refractory animals, which spontaneously reactivated their sexual activity after several months in SD. These changes of expression are not secondary to the photoperiodic variations of gonadal steroids. In contrast, melatonin appears to be necessary for these seasonal changes because pineal-gland ablation prevented the SD-induced downregulation of KiSS-1 expression. Remarkably, a chronic administration of kisspeptin-10 restored the testicular activity of 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 photoperiod, via melatonin, modulates KiSS-1 signaling to drive the reproductive axis.

Suppression of kisspeptin expression and gonadotropic axis sensitivity following exposure to inhibitory day lengths in female Siberian hamsters

“…These results, as well as those from the present study, suggest the possibility that kisspeptin responds to levels of sex steroids rather than drives reproductive system involution. However, recent findings in Syrian hamsters (Mesocricetus auratus) indicate that photoperiod drives changes in kisspeptin directly rather than through changes in gonadal steroids (Revel et al, 2006). More specifically, Kiss-1 mRNA in short-day hamsters given testosterone replacement does not differ from short-day controls (Revel et al, 2006).…”

“…However, recent findings in Syrian hamsters (Mesocricetus auratus) indicate that photoperiod drives changes in kisspeptin directly rather than through changes in gonadal steroids (Revel et al, 2006). More specifically, Kiss-1 mRNA in short-day hamsters given testosterone replacement does not differ from short-day controls (Revel et al, 2006). Whether or not photoperiod-induced changes in kisspeptin expression in female hamsters are also independent of gonadal steroids requires further study.…”

Gene structures, biochemical characterization and distribution of rat melatonin receptors

“…GnRH neurons are central regulators of the reproductive axis. Several lines of evidence suggest that melatonin regulates GnRH neuronal activity and GnRH secretion through afferent neurons modulating the GnRH neuronal system [25][26][27]. However, direct regulatory actions of melatonin on GnRH neurons are still unknown.…”

Kisspeptin signaling in the brain: Recent developments and future challenges

“…These may include, among others, melatonin, neuropeptide Y and IGF-1 [33][34][35], although their roles in the physiologic control of the KISS1 system in different conditions (from changes in photoperiod to metabolic stress) have not been conclusively defined and merit further investigation. Intriguingly, recent work in sheep has revealed that Kiss1 neurons at the ARC co-express dynorphin (Dyn) and neurokinin-B (NKB) [36], which might operate as A c c e p t e d M a n u s c r i p t Kisspeptin signaling in the brain 7 auto-regulatory signals for kisspeptin neurons in the mouse also.…”