Ghrelin, the endogenous ligand of the GH secretagogue receptor (GHS-R), has been recently demonstrated as a pleiotropic regulator involved in a large array of endocrine and non-endocrine functions, including food intake and energy balance (see newsletter # 27). However, the potential reproductive role of this newly discovered molecule has remained largely neglected. Several lines of evidence strongly suggest the involvement of ghrelin in the control of some aspects of gonadal function.

Expression of ghrelin has been demonstrated in mature Leydid cells of rat and human testes, as well as in steroidogenically active lacteal and interstitial hilus cells of the ovary. In addition, expression of the functional ghrelin receptor, the GHS-R type 1a, has been shown in Sertoli and Leydig cells of the testes, and in follicular, luteal, surface epithelial and interstitial hilus cells of the ovary. In terms of function, ghrelin has been proven to dose-dependently inhibit testicular testosterone secretion in vitro, and to modulate Leydig cell proliferation in vivo, as well as the expression of relevant testicular genes, such as that encoding stem cell factor.

Moreover, extragonadal actions of ghrelin upon the reproductive axis have been reported. Ghrelin was able to suppress LH secretion in vivo, and to decrease LH responsiveness to GnRH in vitro. In summary, the data so far available strongly suggest that through local and/ or systemic actions, ghrelin operates as a novel regulator of gonadal function that may contribute to the integrated control of energy balance and reproduction.

Tena-Sempere, M. Growth Hormone & IGF-I Research 15 (2005) 83-88.

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