Ghrelin: novel regulator of gonadal function.

Ghrelin, the endogenous ligand of the GH secretagogue receptor (GHS-R), has been recently involved in the regulation of a large array of endocrine and non-endocrine functions, including the control of GH secretion, food intake and energy balance. However, despite the proven link between energy homeostasis and fertility, and the clear-cut reproductive effects of other regulators of energy homeostasis and growth, the potential role of ghrelin in the control of gonadal function has so far received little attention. We review herein our recent work on the characterization of the expression and biological actions of ghrelin in rat and human gonads. Expression of ghrelin was demonstrated in mature Leydig cells of rat and human testis, as well as in steroidogenically active luteal and interstitial hilus cells of the ovary. Gonadal expression of the functional ghrelin receptor, the GHS-R type 1a, was also shown in Sertoli and Leydig cells of the testis and in follicular, luteal, surface epithelial and interstitial hilus cells of the ovary. In terms of function, ghrelin inhibited in a dose-dependent manner, stimulated testicular testosterone secretion in vitro and modulated Leydig cell proliferation in vivo as well as the expression of relevant testicular genes, such as that encoding stem cell factor. Additional reproductive effects of ghrelin have been recently substantiated, as ghrelin was able to both suppress LH secretion in vivo and decrease LH responsiveness to GnRH in vitro. Overall, it is proposed that, through systemic and local actions, ghrelin may cooperate with other key regulatory signals, such as leptin, in the integrated control of energy balance and gonadal function.