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 journalArticlepeer-review

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 2008


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

ASJC Scopus subject areas

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


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