Ghrelin, the gonadal axis and the onset of puberty.

Puberty onset and reproduction are metabolically gated; conditions of energy insufficiency are associated to perturbations in the timing of puberty and subfertility. The neuroendocrine basis for this phenomenon relies on the regulatory actions of a diversity of nutritional and metabolic cues as well as hormones controlling energy homeostasis at different levels of the reproductive axis. Among these, experimental evidence from different species, including rodents and primates, has accumulated in recent years to strongly suggest that the gut hormone, ghrelin, which operates as signal of energy insufficiency and functional antagonist of leptin, may play a physiological, and eventual pathophysiological role in the regulation of puberty onset and gonadal function. Such a 'reproductive' dimension of ghrelin is likely to include, among others, its ability to modulate gonadotropin secretion, to influence the timing of puberty and to directly regulate gonadal (both testicular and ovarian) functions. In keeping with its proposed role as signal for energy deficit, most of the reported actions of ghrelin upon the reproductive axis appear to be inhibitory, thus suggesting that ghrelin may convey at least part of the suppressive effects of low body fuel stores and energy insufficiency on puberty and fertility.