Novel signals for the integration of energy balance and reproduction

Although the close link between body weight and fertility has been known for eons, only recently have the peripheral signals and neuroendocrine networks responsible for such a phenomenon begun to be identified. A key event in this field was the cloning of the adipocyte-derived hormone leptin, which has been demonstrated as a pivotal regulator for the integration of energy homeostasis and reproduction. In addition, other metabolic hormones, such as insulin, contribute to this physiological integration. Moreover, compelling experimental evidence implicates hormonal products of the gastrointestinal tract as adjuncts in the complex coordination and regulation of body weight and reproduction. Here, we review recent studies evaluating the reproductive effects and sites of action of ghrelin and PYY3-36, two hormonal signals of gastrointestinal origin involved in the control food intake and energy balance. In addition, we summarize the potential contribution of kisspeptin, the recently characterized gatekeeper of the GnRH system encoded by Kiss1 gene, to integrating reproductive function and energy status. Evidence suggests that besides having direct gonadal effects, ghrelin may participate in the regulation of gonadotropin secretion and it may influence the timing of puberty. Likewise, PYY3-36 modulates GnRH and gonadotropin release. In addition, the hypothalamic KiSS-1 system is sensitive to nutritional status, and its diminished expression during states of negative energy balance might contribute to the suppression of reproductive function in such conditions. We propose that the peripheral hormones, ghrelin and PYY3-36, and the central neuropeptide, kisspeptin, are 'novel' players in the neuroendocrine networks that integrate energy balance and reproduction.