Figure 3.

Working model indicating how the photo-inhibitory melatonergic message in short day conditions is integrated in the hypothalamus to further regulate the gonadotropic axis of the male Syrian hamster. GnRH neurons located in the preoptic area (POA) project at the median eminence to release GnRH which stimulates the release of pituitary gonadotropins downstream. GnRH neuron activity is regulated upstream by two populations of peptidergic neurons, the kisspeptin neurons located in the anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, and the RFRP neurons located in the dorsomedial hypothalamus (DMH). Kisspeptin expression is up-regulated in the AVPV and down-regulated in the ARC by sex steroids. Of note, female AVPV contains a much higher number of kisspeptin neurons which are critical for the LH surge. ARC kisspeptin is regulated by metabolic factors and inhibited indirectly by melatonin. Kisspeptin is released at the level of GnRH cell bodies and nerve endings to induce GnRH secretion. RFRP neurons project to the GnRH neurons and possibly toward the ARC kisspeptin neurons. Although usually described as a gonadotropic inhibitor in other species, RFRP-3 induces a clear increase in GnRH neuron activity, kisspeptin expression, and testosterone production in the male Syrian hamster. In short days, the larger production of melatonin inhibits RFRP expression in a sex steroid-independent manner. This in turn reduces ARC kisspeptin expression and decreases gonadotropin secretion. Thus, RFRP neurons appear pivotal for the melatoninergic regulation of reproductive activity in seasonal rodents, although the pineal hormone may not act directly on RFRP neurons.