Stimulation of gonadotropin secretion in prepubertal monkeys after hypothalamic excitation with aspartate and glutamate.

Abstract

To test the hypothesis that aspartate (Asp) and glutamate (Glu) can be used to probe the functional integrity of the GnRH neuron, the dose-response relationships between i.v. administered, endogenously occurring amino acids (Asp and Glu) and GnRH release were determined in the prepubertal male monkey. GnRH release was assessed indirectly by monitoring the LH response by the pituitary, the sensitivity of which had been heightened by prior exposure to pulsatile GnRH. Four of these animals received an i.v. bolus of 0, 1.5, 4.8, 15, 48 and 150 mg/kg BW of each of the amino acids. Plasma gonadotropin and amino acid concentrations were measured immediately before and for 3 hours after administration of Asp and Glu. The 150 mg/kg dose of both amino acids resulted in a dramatic rise in plasma LH concentrations that peaked at 10 min after injection. At this dose plasma Asp and Glu levels increased 200-fold and 50-fold, respectively. No significant LH release was seen with any of the lower doses. These results indicate that i.v. administration of these acidic amino acids in prepubertal monkeys stimulates GnRH release. Based upon this observation, we hypothesize that Asp or Glu could be used to develop a clinical test of GnRH neuronal function.