We have studied the effects of various anesthetics on the spontaneous release of gonadotropin-releasing hormone (GnRH) into hypophysial portal vessel blood and used the techniques of prolonged electrical stimulation of the hypothalamus and iv infusion of GnRH to determine more precisely the relationships between GnRH and LH release and between stored hormone and the amount released. A surge of GnRH (measured by RIA) occurred at the expected time of the spontaneous surge of plasma LH in rats anesthetized on proestrus with Althesin (alphaxalone and alphadolone acetate) but not in rats anesthetized with α-chloralose, ketamine hydrochloride, or urethane. The average amount of GnRH released into portal blood during the surge (128 pg) was relatively small compared to the amount stored in the hypothalamus (6-8 ng). Electrical stimulation of the medial preoptic area in rats anesthetized with urethane produced a surge of LH that was similar to the spontaneous LH surge. This induced surge of LH was preceded by a relatively small increase in the GnRH output (proportional to current strength) but was not accompanied by a significant change in the hypothalamic GnRH content or the pituitary LH content. The iv infusion of GnRH in rats anesthetized with urethane at a rate that produced peripheral plasma concentrations of GnRH similar to those in portal blood during the spontaneous surge in Althesin-treated rats evoked a surge of LH with a height similar to that of the spontaneous LH surge. These results show that 1) the amount of GnRH that needs to be released to evoke a surge of LH at proestrus is very small relative to the amount stored in the hypothalamus (∼ 2%), 2) the timing and duration of the LH surge are determined by the timing and duration of the GnRH surge, and 3) chloralose, ketamine hydrochloride, and urethane block spontaneous GnRH release.
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