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RAPID REPORT |
1 Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Córdoba, Spain
2 Department of Physiology, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
The awakening of the gonadotrophic axis at puberty is the end-point of a complex cascade of sex developmental events that leads to the attainment of reproductive capacity. Recently, loss-of-function mutations of the gene encoding GPR54, the putative receptor for the KiSS-1-derived peptide metastin, have been linked to hypogonadotrophic hypogonadism, both in rodents and humans. However, the actual role of the KiSS-1/GPR54 system in the timing of puberty onset remains unexplored. We report herein that chronic central administration of KiSS-1 peptide to immature female rats induced the precocious activation of the gonadotrophic axis, as estimated by advanced vaginal opening, elevated uterus weight, and increased serum levels of luteinizing hormone (LH) and oestrogen. The central effect of KiSS-1 upon LH release appeared to be mediated via the hypothalamic LH-releasing hormone. In contrast, despite the well-documented permissive role of body fat stores and the adipocyte-derived hormone leptin in puberty maturation, acute activation of the gonadotrophic axis by KiSS-1 was persistently observed in pubertal animals under food deprivation, after central immunoneutralization of leptin, and in a model of leptin resistance. Overall, the present results, together with our recent data on maximum expression of KiSS-1 and GPR54 genes in the hypothalamus at puberty, provide novel evidence for a role of the KiSS-1 system as a downstream element in the hypothalamic network triggering the onset of puberty.
(Received 20 July 2004;
accepted after revision 14 October 2004;
first published online 14 October 2004)
Corresponding author M. Tena-Sempere: Physiology Section. Department of Cell Biology, Physiology and Immunology. Faculty of Medicine, University of Córdoba, Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain. Email: fi1tesem{at}uco.es
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