DIFFERENTIAL GONADOTROPIN RESPONSES TO N-METHYL-D,L-ASPARTATE IN INTACT AND CASTRATED MALE-RATS

Peripheral administration of N-methyl-D,L-aspartate (NMA), a neuroexci tatory amino acid agonist, probably stimulates 1,H release through an increase in endogenous LHRH secretion. In the present study, NMA and a potent LHRH antagonist were used to determine the degree to which rel ease of FSH is similarly dependent upon the acute secretion of LHRH. A second aim was to compare responsiveness of LHRH neurons to NMA in ca strated and intact male rats. Adult male rats were castrated (n = 10) or sham castrated (n = 11) on the morning of Day 0. After 8 days, rats were fitted with atrial catheters between 0900 and 1200 h; at 2 100 h they received s.c. either oil vehicle or 100 mug of an LHRH antagonis t. Starting at 0900 h on Day 9, 0.5-ml blood samples were collected ev ery 10 min for 3 h. After 1 h of sampling each animal received i.v. 5 mg of NMA in 0.5 ml 0.9% saline. An hour later each rat received i.v. 500 ng of LHRH in 0.5 ml saline. Plasma LH, FSH, and prolactin (PRL) l evels were determined by RIA. In the oil-treated sham castrates, mean plasma LH levels were increased by 110% (p < 0.0 1) within 10 min and remained elevated for 30 min after the injection of NMA. The profile o f this LH secretory response was similar to or slightly more robust th an endogenous LH pulses observed previously. The NMA-induced I.H relea se was completely blocked by pretreatment with LHRH antagonist. In bot h oil- and antagonist-treated sham-castrated rats, NMA administration failed to elicit a concomitant increase in plasma FSH levels. In both castrated groups, neither LH nor FSH release was elevated after admini stration of NMA. Treatment with NMA produced similar PRL increments in sham-castrated and castrated groups. In all animals, the injection of LHRH stimulated robust increases in LH secretion and much smaller inc reases in FSH release. Our data indicate that although a large dose of exogenous LHRH can stimulate FSH release, the amount of endogenously secreted LHRH required to induce a pulse of LH is inadequate to stimul ate a coincident pulse of FSH secretion. Thus, it is hypothesized that FSH secretion is regulated by two or more mechanisms; LHRH maintains, in part, basal secretion of FSH, while pulse-like increments in FSH s ecretion arc either constitutive endocrine events or are driven by a s eparate hypothalamic FSH-releasing factor. On the basis of our second major finding-that NMA-stimulated LH secretion is attenuated in castra ted rats-it is also hypothesized that the readily releasable pool of L HRH is diminished following castration.