Fasting-Induced Suppression of LH Secretion Does Not Require Activation of ATP-Sensitive Potassium (KATP) Channels

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 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, were infused into the lateral cerebroventricle in ovariectomized mice that were either fed or fasted for 48 hours. Tolbutamide infusion resulted in a two-fold increase in LH concentrations in both fed and fasted mice compared to both fed and fasted vehicle-treated mice. However, tolbutamide did not reverse the suppression of LH in the majority of fasted animals. In SUR1 null mutant mice (SUR1), which are deficient in KATP channels, and their wild type (WT) littermates, a 48hr fast was found to reduce serum LH concentrations in both WT and SURmice. 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 GnRH release, but are not obligatory for mediating the effects of fasting on GnRH/LH secretion. Thus, it is unlikely that the modulation of KATP 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.