Reinitiation of Ovulatory Cycles in Pituitary Stalk-Sectioned Rhesus Monkeys: Evidence for a Specific Hypothalamic Message for the Preovulatory Release of Luteinizing Hormone*

Abstract
Female rhesus monkeys received intermittently infused GnRH after their pituitary stalks had been sectioned and either a Teflon or a Silastic barrier had been placed between the cut ends of the stalk. This mode of GnRH infusion (1 μg/ min for 6 min each hour) caused follicular development and an increase in serum 17β-estradiol (E2) levels to between 200–300 pg/ml, but did not result in ovulation in animals with Teflon barriers. Basal serum LH and FSH levels in these animals were comparable to those observed in intact cycling monkeys. In three animals with Silastic barriers (0.13 or 0.65 mm thick), the identical GnRH treatment resulted in follicular growth and ovulation. To determine if Silastic membranes could serve as a barrier against GnRH, we constructed Silastic capsules (wall thickness, 0.65 mm), filled them with GnRH, and implanted them sc into ovariectomized hamsters primed with E2. There was an increase (P < 0.05) in serum GnRH in animals treated with GnRH capsules, and serum LH was greater (P < 0.05) in animals with GnRH capsules than in those with empty capsules. The elevation in LH was maintained for at least 2 h. Additional in vitro experiments showed that somatostatin and gastrin, but not β-endorphin, can also diffuse through Silastic membranes. Since we had shown that Silastic membranes do not provide an effective barrier against small hypothalamic peptides that can influence pituitary secretion, and since we suspected that the message for ovulatory LH release was increased GnRH release, two additional stalk-sectioned monkeys with Teflon barriers received episodically infused GnRH and, in addition, were given 24 h of continuous GnRH when serum E2 had been elevated to 150 pg/ml for 2 consecutive days. Both animals showed a LH surge and ovulated in response to continuous GnRH infusion. All stalk-sectioned monkeys, regardless of the type of barrier used to separate the pituitary from the hypothalamus, showed hyperprolactinemia. The data are consistent with the hypothesis that increased serum E2 elicits increased GnRH release from the hypothalamus, which then acts on an E2-primed pituitary to cause the preovulatory release of LH.