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

Wenyu Huang, Maricedes Acosta-Martínez, Teresa H. Horton, Jon E. Levine

Research output: Contribution to journalArticle

10 Scopus citations


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 (KATP) 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 KATP 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 KATP 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 KATP 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 KATP 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.

Original languageEnglish (US)
Pages (from-to)E1439-E1446
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6
StatePublished - Dec 1 2008


  • Gonadotropin-releasing hormone
  • Luteinizing hormone
  • Metabolic signals
  • Sulfonylurea

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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