EFFECT OF ACUTE GLUCOSE ANTAGONISM ON HYPOPHYSEAL HORMONES AND CONCENTRATIONS OF INSULIN-LIKE GROWTH-FACTOR (IGF)-I AND IGF-BINDING PROTEINS IN SERUM, ANTERIOR-PITUITARY, AND HYPOTHALAMUS OF EWES

The objectives of this study were to determine whether 2-deoxy-D-gluco se (2DG), a metabolic inhibitor of glucose, 1) differentially affected release of LH, growth hormone (GH) and prolactin (PRL); 2) decreased anterior pituitary response to GnRH; and 3) altered concentrations of insulin-like growth factor I (IGF-I) and intensity of I-125-IGF-I bind ing to proteins (IGFBPs) in serum, anterior pituitary (AP) and hypotha lamus (preoptic area [POA], medial basal hypothalamus [MBH], and stalk median eminence [SME]). In trial 1, mature, ovariectomized, crossbred ewes were treated with a single s.c. injection of either saline (n = 5) or 2DG (n = 5: 0.1 g/kg BW). Administration of 2DG suppressed (p < 0.05) concentrations of LH but did not affect (p > 0.05) serum concent rations of GH or PRL. In trial 2, ovariectomized ewes received injecti ons of saline or 2DG, and each group was subdivided to receive either saline or GnRH analog (5 mu g; Des-Gly(10)-[D-Ala(6)]) 2 h later. Admi nistration of 2DG suppressed (p < 0.05) serum concentrations of LH bef ore administration of GnRH; however, release of LH in response to exog enous GnRH was greater (p < 0.05) in ewes that received 2DG. Treatment with 2DG did not affect (p > 0.05) concentrations of FSH before or af ter administration of GnRH. In trial 3, 10 ovariectomized ewes were sl aughtered 2 h after treatment with saline (n = 5) or 2DG (n = 5). Seru m and tissues collected at slaughter (AP, MBH, SME, and POA) were anal yzed for concentrations of IGF-I by RIA and intensity of I-125-IGF-I b inding to proteins by ligand blotting. Concentrations of IGF-I in seru m and tissues were not affected (p > 0.05) by treatment with 2DG. IGFB Ps were detected in serum, AP, and SME of all ewes, but intensity of I -125-IGF-I binding to proteins was not affected (p > 0.05) by treatmen t with 2DG. In summary, treatment with 2DG decreased release of LH. Th e suppression of LH did not appear to be caused by direct actions of 2 DG on the AP, because response to exogenous GnRH was enhanced in ewes treated with 2D)G. Concentrations of IGF-I and IGF-I binding activity in the AP, MBH, POA, or SME were not altered 2 h after treatment with 2DG. This research demonstrates that depletion of glucose availability in ewes suppresses release of LH, presumably by actions at the hypoth alamus or higher neural centers.