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Submitted on November 3, 2005
Accepted on February 17, 2006
Department of Cell Biology, Physiology and Immunology, University of Córdoba, 14004 Córdoba, Spain; and Departments of Physiology and Medicine, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
* To whom correspondence should be addressed. E-mail: fi1tesem{at}uco.es.
The ability of kisspeptins, ligands of the G protein-coupled receptor GPR54, to potently elicit LH secretion is now undisputed. Yet, most of the pharmacological characterization of their gonadotropin-releasing effects has been conducted after intracerebral administration. In contrast, the effects of peripheral injection of kisspeptin remains much scarcely defined. In this study, dynamic LH secretory responses to intravenous (i.v.) administration of kisspeptin-10 in different experimental settings are presented, and compared with those evoked by kisspeptin-52, using a protocol of serial blood sampling in conscious, freely-moving male rats. LH responsiveness to peripheral administration of kisspeptin appeared extremely sensitive, as doses as low as 0.3 nmol/kg (0.1 µg/rat) evoked robust LH bursts, whose magnitude was dose-dependent and apparently maximal in response to 3.0 and 30 nmol/kg kisspeptin-10. The ability of kisspeptin-10 to stimulate LH release was fully preserved, and even doubled in terms of relative increases, after short-term fasting despite suppression of prevailing LH levels. Repeated injections of kisspeptin-10 (4 boluses, at 75-min intervals) evoked associated LH secretory pulses, whose magnitude remained constant along the study-period. Moreover, in this setting, in vivo LH responses to a terminal injection of GnRH were preserved, while basal and depolarization-induced GnRH release ex vivo was significantly enhanced. Finally, i.v. administration of kisspeptin-52 elicited dynamic LH responses analogous to that of kisspeptin-10; yet, their net magnitude and duration was slightly greater. In summary, we present herein a series of experiments on the effects of systemic (i.v.) injection of single or repeated doses of kisspeptin upon dynamic LH secretion in conscious male rats. Besides potential physiologic relevance, our present data might contribute to set the basis for the rational therapeutic use of kisspeptin analogs in the pharmacological manipulation of the gonadotropic axis.
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