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Am J Physiol Endocrinol Metab (April 15, 2008). doi:10.1152/ajpendo.90240.2008
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Submitted on February 18, 2008
Revised on March 31, 2008
Accepted on April 10, 2008

Desensitization of Gonadotropin Responses to Kisspeptin in the Female Rat: Analyses of LH and FSH Secretion at Different Developmental and Metabolic States

Juan Roa1, Eva Vigo, David Garcia-Galiano1, Juan Manuel Castellano2, Victor Manuel Navarro2, Rafael Pineda, Carlos Dieguez MD3, Enrique Aguilar, Leonor Pinilla, and Manuel Tena-Sempere2*

1 University of Cordoba, Spain
2 University of Cordoba
3 U. Santiago de Compostela

* To whom correspondence should be addressed. E-mail: fi1tesem{at}uco.es.

Kisspeptins have emerged as potent elicitors of gonadotropin secretion, and so, putative targets for pharmacological intervention. In this context, desensitization of gonadotropin responses to continuous administration of kisspeptins has begun to be characterized, but information so far available is mostly restricted to LH responses in males, whereas the similar phenomenon in females, of obvious therapeutic interest, remains virtually unexplored. We report herein LH and FSH responses to continuous intracerebral administration of kisspeptin in female rats, at different developmental and metabolic states. Infusion of kisspeptin-10 to adult female rats induced a transient elevation in serum LH concentrations, followed by a precipitous drop and normalization of LH levels thereafter. Elevation of LH after kisspeptin infusion was prolonged in underfed animals; a phenomenon mimicked by leptin administration. Conversely, FSH levels were persistently heightened along continuous kisspeptin infusion, but duration of this response was shortened by undernutrition. In pubertal females, LH and FSH levels remained elevated at the end of 7-d infusion of kisspeptin; responses whose magnitude was augmented by subnutrition but not mimicked by leptin. In all settings, terminal GnRH responses were fully preserved, suggesting that eventual desensitization must occur up-stream the pituitary. In sum, our current data document the pharmacological consequences of continuous administration of kisspeptin to female rats, with remarkable differences being detected between LH and FSH responses, in different developmental and metabolic states. These observations, of potential pharmacological interest, might help also to delineate the physiological roles of kisspeptins in the dynamic regulation of gonadotropin secretion in the female.







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