Role of leptin and ghrelin in the regulation of gonadal function

Abstract

Gonadal development and function is sustained by the complex interaction of an array of regulatory signals that operate directly on the gonads and/or indirectly via modulation of gonadotropin secretion. During the last decade, different factors primarily involved in the control of food intake and energy balance have been demonstrated as putative modulators of different elements of the reproductive axis, including the gonads, thus helping to define the neuroendocrine basis for the link between body energy stores and fertility. These factors include not only the adipocyte-derived hormone leptin, which is indispensable for proper energy balance and reproduction, but also a number of neuropeptides and hormones of central and peripheral origin. In the latter, growing evidence strongly suggests the involvement of the stomach-secreted peptide ghrelin in the control of several aspects of gonadal function. Interestingly, leptin and ghrelin have been proposed as reciprocally related regulators of energy homeostasis; however, their potential interplay in the control of reproduction remains ill defined. This work will summarize the most salient findings concerning the potential roles of leptin and ghrelin in the functional control of the gonads. In addition, open issues regarding the reproductive facets of these metabolic signals will be highlighted. Overall, the authors propose that through complementary or antagonistic actions, leptin and ghrelin may jointly cooperate to modulate a wide set of reproductive functions, thereby contributing to the physiologic integration of energy balance and reproduction.

Keywords::

• energy balance
• ghrelin
• gonadotropin-releasing hormone
• gonadotropins
• G protein-coupled receptor 54
• growth hormone-secretagog receptor
• KiSS-1
• leptin
• ovary
• testis

Acknowledgement

The authors are indebted to Gaytan F, Aguilar E and Pinilla L for helpful discussion during the preparation of this manuscript. The experimental work conducted in the authors’ laboratory was supported by grants BFI 2002–00176 and BFI 2005–07446 from Ministerio de Educacion y Ciencia (Spain), funds from Instituto de Salud Carlos III (Project PI042082, CP04/00158, PI030947, PI042251, PI050319 and PI050798), Xunta de Galicia (PGIDIT05BTF20802PR) and EU research contract EDEN QLK4–CT–2002–00603. The financial support of CIBER–03 (Physiopathology of Obesity and Nutrition) is also acknowledged.