Connecting metabolism and gonadal function: Novel central neuropeptide pathways involved in the metabolic control of puberty and fertility

Albeit essential for perpetuation of species, reproduction is an energy-demanding function that can be adjusted to body metabolic status. Reproductive maturation and function can be suppressed in conditions of energy deficit, but can be altered also in situations of persistent energy excess, e.g., morbid obesity. This metabolic-reproductive integration, of considerable pathophysiological relevance to explain different forms of perturbed puberty and sub/infertility, is implemented by the concerted action of numerous central and peripheral regulators, which impinge at different levels of the hypothalamic-pituitary-gonadal (HPG) axis, permitting a tight fit between nutritional/energy status and gonadal function. We summarize here the major physiological mechanisms whereby nutritional and metabolic cues modulate the maturation and function of the HPG axis. We will focus on recent progress on the major central neuropeptide pathways, including kisspeptins, neurokinin B and the products of POMC and NPY neurons, which convey metabolic information to GnRH neurons, as major hierarchical hub of our reproductive brain.