title: Central, but not peripheral, glucose-sensing mechanisms mediate glucoprivic suppression of pulsatile luteinizing hormone secretion in the sheep.
abstract: Changes in glucose availability are proposed to modulate pulsatile GnRH secretion, and at least two anatomical sites, the liver and hindbrain, may serve as glucose sensors. The present study determined the relative importance of these putative glucose-sensing areas in regulating pulsatile LH secretion in the sheep. Our approach was to administer the antimetabolic glucose analog, 2-deoxy-D-glucose (2DG) into either the hepatic portal vein or the fourth ventricle in gonadectomized females in which LH pulse frequency was high. In the first study, a catheter was placed in the ileocolic vein to determine the effects of local injection of 2DG into the hepatic portal system on the release of LH. After monitoring the pattern of LH secretion for 4 h, 2DG (250 mg/kg) was infused (500 microl/min) into the liver for 2 h. For comparison, animals were also given the same dose of 2DG into a jugular vein for 2 h. Administration of 2DG into either the hepatic portal or jugular vein reduced LH pulse frequency to the same extent. Infusion of the lower dose (50 mg/kg) locally into the hepatic portal vein did not affect plasma LH profiles. Collectively, these results are interpreted to indicate that the liver does not contain special glucose-sensing mechanisms for the glucoprivic suppression of LH pulses. In the second study, 2DG (5 mg/kg) was infused (50 l/min) for 30 min into the fourth ventricle or lateral ventricle. During the subsequent 4-h sampling period, pulsatile LH secretion was significantly suppressed, but there was no significant difference in LH pulse frequency between sites of infusion. Peripheral 2DG concentrations were not detectable after either fourth or lateral ventricle infusions, indicating that the 2DG had acted centrally to suppress LH pulses. Plasma cortisol concentrations increased more in animals infused with 2DG into the fourth ventricle than in those infused into the lateral ventricle, suggesting that 2DG infused into lateral ventricle is transported caudally into the fourth ventricle and acts within the area surrounding the fourth ventricle. Overall, these findings suggest that an important glucose-sensing mechanism is located circumventricularly in the fourth ventricle. Moreover, the liver does not appear to play an important role in detecting glucoprivic action of 2DG to suppress pulsatile LH secretion.
authors: Primate Research Institute, Kyoto University, Aichi, Japan.
authors: S
authors: S
authors: Ohkura
authors: T
authors: T
authors: Tanaka
authors: S
authors: S
authors: Nagatani
authors: D C
authors: DC
authors: Bucholtz
authors: H
authors: H
authors: Tsukamura
authors: K
authors: K
authors: Maeda
authors: D L
authors: DL
authors: Foster
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000502:physiology; D003847:Deoxyglucose / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D005260:Female; D006706:Homeostasis; D006854:Hydrocortisone / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007601:Jugular Veins; D008099:Liver / Q000187:drug effects / Q000502:physiology; D007986:Luteinizing Hormone / Q000378:metabolism*; D010052:Ovariectomy; D010507:Periodicity; D011169:Portal Vein; D012756:Sheep / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007986:Luteinizing Hormone; D003847:Deoxyglucose; D006854:Hydrocortisone