At the Cutting Edge

KiSS-1 and Reproduction: Focus on Its Role in the Metabolic Regulation of Fertility
Manuel Tena-Sempere

Department of Cell Biology, Physiology and Immunology, Physiology Section, University of Córdoba, Córdoba, Spain

Address of Corresponding Author

Neuroendocrinology 2006;83:275-281 (DOI: 10.1159/000095549)

  Key Words

• KiSS-1
• Kisspeptins
• GPR54
• Gonadotropin-releasing hormone
• Gonadotropins
• Energy balance
• Puberty
• Undernutrition
• Diabetes
• Hypogonadism

  Abstract

Unraveling of the master role of kisspeptins, the products of the KiSS-1 gene, and their receptor, GPR54, in the control of reproduction has been a major breakthrough in contemporary neuroendocrinology. Indeed, since the disclosure of their reproductive dimension in late 2003, an ever-growing number of genetic, molecular, physiologic and pharmacological studies have defined the crucial role of KiSS-1 neurons as central processors for the dynamic regulation of the gonadotropic axis and its full activation at puberty. Yet, the potential role of the hypothalamic KiSS-1 system as an intermediary factor for the well-known interplay between energy status and reproduction initially received little attention. Recent data, however, strongly suggest a prominent role of KiSS-1 in the metabolic control of fertility, as expression of KiSS-1 gene at the hypothalamus is down-regulated in conditions of negative energy balance and kisspeptin administration is capable of overcoming the hypogonadotropic state observed in undernutrition and disturbed metabolic conditions. Leptin, the adipocyte hormone signaling the size of body energy stores, is likely to play a pivotal role in the metabolic control of the KiSS-1 system, since kisspeptin neurons express leptin receptors and leptin is able to normalize defective KiSS-1 gene expression in models of impaired gonadotropin secretion linked to hypoleptinemia, such as the ob/ob mouse and streptozotocin-induced diabetic rat. In sum, these data provide strong evidence for a central role of kisspeptins and GPR54 as molecular conduits for the metabolic regulation of reproductive function - a phenomenon with potential physiopathologic and therapeutic implications.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Manuel Tena-Sempere
Department of Cell Biology, Physiology and Immunology
Physiology Section, Faculty of Medicine, University of Córdoba
Avda. Menéndez Pidal s/n, ES-14004 Córdoba (Spain)
Tel. +34 957 218 280, Fax +34 957 218 288, E-Mail fi1tesem@uco.es

  Article Information

Received: July 25, 2006
Accepted: July 27, 2006
Published online: August 29, 2006
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 0, Number of References : 36