Gonadal function is primarily driven by the tropic actions of pituitary gonadotropins (LH and FSH), whose secretion is in turn regulated by the hypothalamic decapeptide GnRH. This neuro-hormonal axis (namely, the HPG axis) is under the modulation of a wide diversity of regulatory signals, which include metabolic cues and factors controlling energy homeostasis. Among those, a dominant role of leptin, the adipose hormone signaling energy sufficiency, in the control of gonadal function has been substantiated in the last decade; leptin being a major effector for the metabolic regulation of fertility, at different levels of the HPG axis. Recent experimental data suggest that the gut hormone ghrelin, as signal of energy insufficiency and functional antagonist of leptin, may operate also as pleiotropic modulator of gonadal function and the reproductive axis. Such regulatory actions appear to be multi-faceted, as i) ghrelin has been shown to inhibit luteinizing hormone (LH) secretion in rodents and other mammals (including humans); ii) ghrelin operates a negative modifier of puberty onset in (male) rats; iii) ghrelin and its canonical receptor (the GHS-R1a) are expressed (and regulated) in the gonads; and iv) ghrelin is able to conduct direct gonadal actions; testicular effects of ghrelin include inhibition of testosterone secretion, Leydig cell proliferation and expression of relevant Sertoli cell genes. Thus, through direct and indirect actions, ghrelin has recently emerged as putative modulator of gonadal function, with predominant inhibitory effects in line with its proposed role as signal of energy insufficiency. Overall, it is tempting to propose that, in addition to classical metabolic regulators (such as leptin), the gut hormone, ghrelin, is a novel player in the dynamic regulation of gonadal function, which might contribute to the integration of energy balance and reproduction.
03 - 07 May 2008
European Society of Endocrinology