Abstract
In several species, IV or SC administration of NMA, a neuroexcitatory analog of aspartate, elicits a pulse of LH secretion. In prepubertal monkeys, chronic intermittent administration of NMA induces pubertal development through a putative hypothalamic action (Plant TM et al, Endocrine Soc, Meeting, 1987, Abst. 65). In order to get a direct insight into this mechanism, GnRH releast from the rat hypothalamus was studied in vitro in the presence of NMA. Concentrations ≤ 0.74 mg/ml were not effective. Incubation with NMA 1.47 mg/ml for 7.5 min resulted in an increase of GnRH release from 11.5 ± 4.3 to 36.2 ± 14.1 pg/0.5 ml (mean ± SD, n= 12). The effect of NMA in vivo was evaluated by studying rats sacrificed at different times after SC injection of 30 mg/kg of NMA. One, 3, 5, 7.5 and 10 min after NMA injection, mean serum LH rose progressively (32.0, 38.0, 70.0, 71.0 and 87.5 ng/ml, respectively). The hypothalami of these rats were immediately dissected and studied in vitro. One, 3, 5, 7.5 and 10 min after NMA injectior in vivo, mean GnRH release in vitro showed a marked increase (20.0, 32.0, 46.3, 115.5 and 41.8 pg/0.5 ml, respectively), indicating that CnRH is likely the neuroendocrine mediator of NMA-induced LH secretion. The study of GnRH release by NMA in vitro provides a means to further elucidate the mechanisms of the hypothalamic pulse generator and its role in the initiation of puberty.
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