HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/E1439    most recent 90615.2008v2 90615.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Huang, W. Articles by Levine, J. E. Search for Related Content PubMed PubMed Citation Articles by Huang, W. Articles by Levine, J. E.

Fasting-induced suppression of LH secretion does not require activation of ATP-sensitive potassium channels

Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois

Submitted 21 July 2008 ; accepted in final form 3 October 2008

Reproductive hormone secretions are inhibited by fasting and restored by feeding. Metabolic signals mediating these effects include fluctuations in serum glucose, insulin, and leptin. Because ATP-sensitive potassium (K_ATP) channels mediate glucose sensing and many actions of insulin and leptin in neurons, we assessed their role in suppressing LH secretion during food restriction. Vehicle or a K_ATP channel blocker, tolbutamide, was infused into the lateral cerebroventricle in ovariectomized mice that were either fed or fasted for 48 h. Tolbutamide infusion resulted in a twofold increase in LH concentrations in both fed and fasted mice compared with both fed and fasted vehicle-treated mice. However, tolbutamide did not reverse the suppression of LH in the majority of fasted animals. In sulfonylurea (SUR)1-null mutant (SUR1^–/–) mice, which are deficient in K_ATP channels, and their wild-type (WT) littermates, a 48-h fast was found to reduce serum LH concentrations in both WT and SUR^–/– mice. The present study demonstrates that 1) blockade of K_ATP channels elevates LH secretion regardless of energy balance and 2) acute fasting suppresses LH secretion in both SUR1^–/– and WT mice. These findings support the hypothesis that K_ATP channels are linked to the regulation of gonadotropin-releasing hormone (GnRH) release but are not obligatory for mediating the effects of fasting on GnRH/LH secretion. Thus it is unlikely that the modulation of K_ATP channels either as part of the classical glucose-sensing mechanism or as a component of insulin or leptin signaling plays a major role in the suppression of GnRH and LH secretion during food restriction.

sulfonylurea; luteinizing hormone; gonadotropin-releasing hormone; metabolic signals