Gonadotropin-releasing hormone fibers contact POMC neurons in the hypothalamic arcuate nucleus.

The metabolic state has long been shown to affect reproduction. Peripheral signals and hormones from the reproductive organs are also known to regulate energy metabolism and feeding and energy expenditure. Much attention has been paid to determine the signaling flow from key hypothalamic neuronal populations, including those producing the anorexigenic proopiomelanocortin (POMC) derivate, α-melanocyte stimulating hormone (α-MSH), to the medial preoptic area gonadotropin-releasing hormone (GnRH) neurons, cells that are the drivers of ovulation and reproduction in general. In this study, the authors explored whether a reverse signaling modality may also exist. Specifically, the authors analyzed GnRH efferents in the arcuate nucleus with particular emphasis on their anatomical proximity to arcuate nucleus melanocortin perikarya. Using correlated light and electron microscopy, the authors observed direct apposition between GnRH-containing axon terminals and POMC cell bodies. These data provide the first experimental evidence to suggest that GnRH may have a direct influence on feeding, energy expenditure, and glucose homeostasis, independent of the activity of the gonadal axis.