Differential gonadotropin responses to N-methyl-D,L-aspartate in intact and castrated male rats

F. J. Strobl, U. Luderer, L. Besecke, A. Wolfe, N. B. Schwartz, J. E. Levine

Research output: Contribution to journalArticlepeer-review

Abstract

Peripheral administration of N-methyl-D,L-aspartate (NMA), a neuroexcitatory amino acid agonist, probably stimulates LH 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 release of FSH is similarly dependent upon the acute secretion of LHRH. A second aim was to compare responsiveness of LHRH neurons to NMA in castrated 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 2100 h they received s.c. either oil vehicle or 100 μg of an LHRH antagonist. Starting at 0900 h on Day 9, 0.5-ml blood samples were collected every 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) levels were determined by RIA. In the oil-treated sham castrates, mean plasma LH levels were increased by 110% (p < 0.01) within 10 min and remained elevated for 30 min after the injection of NMA. The profile of this LH secretory response was similar to or slightly more robust than endogenous LH pulses observed previously. The NMA-induced LH release was completely blocked by pretreatment with LHRH antagonist. In both 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 administration 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 increases 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 stimulate 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 secretion are either constitutive endocrine events or are driven by a separate hypothalamic FSH-releasing factor. On the basis of our second major finding - that NMA-stimulated LH secretion is attenuated in castrated rats - it is also hypothesized that the readily releasable pool of LHRH is diminished following castration.

Original languageEnglish (US)
Pages (from-to)867-873
Number of pages7
JournalBiology of reproduction
Volume48
Issue number4
DOIs
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

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