Kisspeptin and the seasonal control of reproduction in hamsters

Abstract

Reproduction is a complex and energy demanding function. When internal and external conditions might impair reproductive success (negative energy balance, stress, harsh season) reproductive activity has to be repressed. Recent evidence suggests that these inhibitory mechanisms operate on Kiss1-expressing neurons, which were recently shown to be implicated in the regulation of GnRH release. Hamsters are seasonal rodents which are sexually active in long photoperiod and quiescent in short photoperiod. The photoperiodic information is transmitted to the reproductive system by melatonin, a pineal hormone whose secretion is adjusted to night length. The photoperiodic variation in circulating melatonin has been shown to synchronize reproductive activity with seasons, but the mechanisms involved in this effect of melatonin were so far unknown. Recently we have observed that Kiss1 mRNA level in the arcuate nucleus of the Syrian hamster is lower in short photoperiod, when animals are sexually quiescent. Notably, intracerebroventricular infusion of Kiss1 gene product, kisspeptin, in hamsters kept in short photoperiod is able to override the inhibitory photoperiod and to reactivate sexual activity. The inhibition of Kiss1 expression in short photoperiod is driven by melatonin because pinealectomy prevents decrease in Kiss1 mRNA level in short photoperiod and melatonin injection in long photoperiod down regulates Kiss1 expression. Whether melatonin acts directly on arcuate Kiss1 expressing neurons or mediates its action via interneurons is the subject of the current investigations.

Introduction

Anticipation and adaptation to the upcoming daily and seasonal variations of the environment are a prerequisite for individual and species survival. Light, the intensity of which changes reliably throughout the day and the year, is the major environmental cue used to synchronize daily and seasonal functions.

Using classical genetic models, major advances have been made in recent years to understand the molecular processes underpinning daily/circadian rhythmicity and its synchronization by light [25]. In contrast, much less is known about the molecular mechanisms operating on a seasonal time-scale and regulating functions such as reproduction, body weight regulation, hibernation, migration. This is mostly due to our lack of knowledge on the genetic background of available seasonal models and to the absence of an identified anatomical locus sustaining seasonal rhythms (equivalent of the suprachiasmatic nucleus).

In recent years, however, comprehensive genetic and comparative analyses in seasonal species have led to the discovery of distinct hypothalamic genes that are differently expressed in response to photoperiod [1], [2], [42], [43], [44], [45], [46], [53], [56].

One of these photoperiod-regulated genes, Kiss1, appears essential to seasonal breeding, because it was recently discovered to be critical for the neuroendocrine regulation of reproduction [41]. The present paper therefore reviews the current data and hypotheses on how photoperiod may synchronize seasonal reproduction through regulation of Kiss1 gene expression.