Fasting-induced suppression of LH secretion does not require activation of ATP-sensitive potassium 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 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.
Huang
Wenyu
W
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois, USA.
Acosta-Martínez
Maricedes
M
Horton
Teresa H
TH
Levine
Jon E
JE
D018528:ATP-Binding Cassette Transporters / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D004435:Eating / Q000502:physiology; D005215:Fasting / Q000502:physiology*; D005260:Female; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D007276:Injections, Intraventricular; D007328:Insulin / Q000378:metabolism; D054086:KATP Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D011955:Receptors, Drug / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D064233:Sulfonylurea Receptors; D014044:Tolbutamide / Q000008:administration & dosage / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; C577508:Abcc8 protein, mouse; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D007986:Luteinizing Hormone; D014044:Tolbutamide