Ghrelin as a pleotrophic modulator of gonadal function and reproduction

Reproductive maturation and function are under the influence of a wide variety of regulatory signals, which include nutritional and metabolic cues, as well as hormones that control energy homeostasis. Evidence is mounting that the gut hormone ghrelin - a putative signal of energy insufficiency and a functional antagonist of leptin - operates as a pleotrophic modulator of gonadal function and reproduction. This Review aims to summarize our current knowledge of the possible reproductive functions of ghrelin, such as the ability to modulate gonadotropin secretion, to influence puberty onset, and to directly regulate gonadal physiology. Notably, most of the actions of ghrelin upon the reproductive axis reported to date are inhibitory. This observation suggests that ghrelin might mediate at least part of the well-known suppressive effect of energy deficit on the onset of puberty, gonadal function and fertility. The reproductive actions of ghrelin have been described in a range of species, including humans, and expression of ghrelin and its canonical receptor has been detected in the gonads. As a consequence, it is tempting to speculate that ghrelin is an integral player in the dynamic regulation of gonadal function, and that through a multifaceted mode of action this hormone contributes to the integration of energy balance and reproduction.