Metabolic influences on neuroendocrine regulation of reproduction

Reproduction is a tightly regulated function in which many mechanisms contribute to ensure the survival of the species. Among those, due to the elevated energy requirements of reproduction, metabolic factors exert a pivotal role in the control of hypothalamic-pituitary-gonadal axis. Although this control may occur at multiple levels of the axis, the majority of interactions between metabolic and reproductive systems take place in the hypothalamus. In this article, we present an overview of the state-of-the-art knowledge regarding the metabolic regulation of reproduction at the central level. We aim to identify the neuroanatomical location where both functions interconnect by discussing the likelihood of each component of the neuronal hierarchical network controlling gonadotropin-releasing hormone (GnRH) release to be first-order responders to metabolic cues, especially the peripheral metabolic signals leptin, insulin, and ghrelin.

Latest evidence suggests that the primary action of leptin, insulin, and ghrelin to regulate reproduction is located upstream of the main central elicitors of gonadotropin release, Kiss1 and GnRH neurons, and neuroanatomically separated from their metabolic action.

The study of the neuronal interactions between the mechanisms governing metabolism and reproduction offers the platform to overcome or treat a number of prevailing metabolic and/or reproductive conditions.