Effect of N-Methyl-d, 1-Aspartate on Luteinizing Hormone Secretion in Ovariectomized Ewes in the Absence and Presence of Estradiol1

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Abstract
N-methyl-d,l-aspartate (NMA), a potent agonist of the neuroexcitatory amino acids aspartate and glutamate, stimulates release of luteinizing hormone (LH) in rats and nonhuman primates. The objective of the experiments described here was to determine the effect of NMA on LH secretion in ovariectomized ewes, in both the absence and presence of estradiol. In Experiment 1, blood samples were collected from 16 ewes every 12 min for 4 h. At Hour 2, ewes received i.v. injections of either 0, 6, 12, or 24 mg NMA/kg body weight dissolved in 0.9% saline (n = 4 per treatment). Mean LH concentrations were unaltered by any dose of NMA (p greater than 0.3). Immediately after completion of Experiment 1, each ewe received an s.c. Silastic implant designed to maintain circulating concentrations of estradiol of approximately 1 pg/ml. Three weeks later, Experiment 2 was conducted, using the same blood sampling regimen and doses of NMA as Experiment 1. The estradiol implants decreased serum LH concentrations in all animals. Treatment with saline failed to alter mean LH concentrations (p greater than 0.3). In contrast, 6, 12, and 24 mg NMA/kg body weight increased mean LH concentrations by 326% (p less than 0.03), 1125% (p less than 0.02), and 441% (p less than 0.0001), respectively. These results demonstrate that exogenous estradiol suppresses LH release in sheep in a manner antagonized by NMA.