title: Further evidence for the role of glucose as a metabolic regulator of hypothalamic gonadotropin-releasing hormone pulse generator activity in goats.
abstract: The present study examined the relative importance of blood glucose vs. free fatty acids as a metabolic signal regulating GnRH release as measured electrophysiologically by multiple-unit activity (MUA) in the arcuate nucleus/median eminence region in ovariectomized, estradiol-treated goats. MUA was recorded before, during, and after: 1) cellular glucoprivation by peripheral infusion of 2-deoxy-d-glucose (2DG; 25, 50, and 75 mg/kg.h, iv); 2) peripheral hypoglycemia in response to various doses (15-195 mU/kg.h, iv) of insulin infusion; and 3) cellular lipoprivation induced by peripheral infusion of sodium mercaptoacetate (MA; 2.4 mg/kg.h alone or combined with 25 mg/kg.h of 2DG, iv), and effects on the interval of characteristic increases in MUA (MUA volleys) were examined. Infusion of the highest dose of 2DG increased the mean interval between MUA volleys, whereas the lower doses of 2DG had no effect on volley interval. The MUA volley intervals lengthened as insulin-induced hypoglycemia became profound. There was a negative correlation between MUA volley intervals and blood glucose concentrations during insulin infusion, and coinfusion of glucose with insulin returned the MUA volley interval to a normal frequency. Infusion of MA alone or MA with 2DG did not increase MUA volley intervals. These findings demonstrate that glucose availability, but not fatty acids, regulates the GnRH pulse generator activity in the ruminant. Glucose is considered a key metabolic regulator that fine-tunes pulsatile GnRH release.
authors.affiliation: Laboratory of Neuroendocrinology, National Institute of Agrobiological Sciences, 2 Ikenodai, Tsukuba 305-8602, Japan. ohkura@affrc.go.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohkura
authors.forename: Toru
authors.initials: T
authors.lastname: Ichimaru
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Itoh
authors.forename: Shuichi
authors.initials: S
authors.lastname: Matsuyama
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamura
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006041:Goats; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D011673:Pulsatile Flow
chemical_list: D000963:Antimetabolites; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone; D003847:Deoxyglucose; D005947:Glucose