Sustained intermittent release of gonadotropin-releasing hormone in the prepubertal male rhesus monkey induced by N-methyl-DL-aspartic acid.
The purpose of the present study was to determine whether gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus of the prepubertal monkey may be prematurely provoked into producing a sustained train of intermittent GnRH release N-methyl-DL-aspartic acid (NMA), an analog of the putative excitatory neurotransmitter aspartate, was used to stimulate the hypothalamus. In order to utilize pituitary luteinizing hormone (LH) secretion as a bioassay of hypothalamic GnRH release, juvenile males were castrated and the responsiveness of their gonadotrophs to GnRH was enhanced prior to the study with a chronic intermittent intravenous infusion of the synthetic decapeptide (0.1 microgram/min for 3 min every hour). Treatment with this regimen of GnRH, which appears to provide the pituitary gonadotrophs with a hypophysiotropic stimulus similar to that produced by the hypothalamus of castrated adults, elicited a pattern of pulsatile LH secretion in prepubertal animals similar to that observed in the open-loop situation in adults. This episodic pattern of LH release was sustained without decrement following termination of GnRH priming and initiation of an intermittent intravenous infusion of NMA (4.5-6.5 mg NMA/kg body weight/pulse, administered over 1 min) delivered at a frequency of 1 pulse/1 h for 50 h. In contrast, an intermittent infusion of the vehicle employed to administer NMA (saline) failed to maintain LH secretion. Administration of the same dose of NMA at a slower frequency of 1 pulse/2 h for 52 h, while also sustaining LH secretion without decrement, resulted in an exaggeration in the LH response.(ABSTRACT TRUNCATED AT 250 WORDS)
Gay
V L
VL
Department of Physiology, University of Pittsburgh School of Medicine, Pa.
Plant
T M
TM
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D016202:N-Methylaspartate; D009919:Orchiectomy; D010507:Periodicity; D012741:Sexual Maturation
D001224:Aspartic Acid; D007987:Gonadotropin-Releasing Hormone; D016202:N-Methylaspartate; D007986:Luteinizing Hormone