METABOLIC INTERFACES BETWEEN GROWTH AND REPRODUCTION .5. PULSATILE LUTEINIZING-HORMONE SECRETION IS DEPENDENT ON GLUCOSE AVAILABILITY

To test the hypothesis that mechanisms controlling the secretion of LH are modulated by glucose availability, the acute effects of glucopriv ation were studied. The model was the gonadectomized male lamb raised on a limited diet of artificial milk. The approach was to monitor LH s ecretion before and after the administration of a competitive antagoni st of glucose metabolism, a-deoxyglucose (2DG). We first determined wh ether LH secretion was influenced by glucose availability by administe ring 2DG at several doses. Peripheral administration of the glucose an tagonist (240 and 480 mg/kg 2DG, single iv injection) transiently decr eased LH pulse frequency, but not LH pulse amplitude. By contrast, LH secretion (frequency or amplitude) was not affected by lower doses (60 or 120 mg/kg) of the glucose antagonist. A second study was conducted to determine whether either the pituitary gland or the GnRH neurosecr etory system per se is directly affected by short term glucoprivation. The competency of the pituitary was assessed by administering GnRH du ring the time when LH secretion is suppressed by pharmacological gluco se blockade. Similarly, the function of the GnRH neurosecretory system was assessed by administering a GnRH secretagogue (N-methyl-D,L-aspar tate) under the same glucoprivic conditions. In response to an optimiz ed iv dose of 2DG, LH pulse frequency decreased. However, in lambs tha t received either GnRH or N-methyl-D,L-aspartate during the period of glucoprivation, LH pulse frequency was sustained at levels comparable to those before 2DG was given. To determine whether the effect of gluc oprivation was central in origin, the glucose antagonist was administe red into the lateral cerebral ventricle at 1/100th the doses used peri pherally. Central administration of 2DG, independent of dose, transien tly decreased LH pulse frequency, but not pulse amplitude. However, un like the case with peripheral injection, plasma glucose values did not change after the administration of any dose of 2DG tested centrally. These findings indicate that glucose availability in the developing sh eep influences LH secretion. Moreover, based upon analysis of LH pulse frequency, glucoprivation does not directly impair either the pituita ry gland or the GnRH neurosecretory system. Collectively, these result s suggest that glucose availability affects LK secretion by acting wit hin the central nervous system at a detection site(s) peripheral to th e GnRH neuron.