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  • Title: [Mechanism of LH release with synthetic LH-RH (author's transl)].
    Author: Koyama T.
    Journal: Nihon Naibunpi Gakkai Zasshi; 1976 Sep 20; 52(9):881-97. PubMed ID: 828583.
    Abstract:
    The purpose of this study is to examine the effect of LH-RH on LH release in the baboon. Fifteen female baboons having the normal menstrual cycle were used for this study. On hundred mug of synthetic LH-RH was injected subcutaneously in both the early follicular phase and the early luteal phase. For control purposes, 1 ml of saline was injected subcutaneously in the luteal phase. Blood samples were collected by femoral vein puncture with light anesthesia under prearranged schedule and were assayed for LH-RH, LH, estrogen and progestin. The plasma level of LH-RH reached a maximum within 4 minutes after s.c. injection of 100 mug LH-RH, decreased sharply at first, and then slowly later. Fast and slow disappearance components (t1/2 = 4.7 min., 37.1 min. respectively) were observed. In the baboon given LH-RH during the luteal phase, peaks in plasma levels of LH were observed within 30 minutes and within 90 to 150 minutes after injection. A lesser pituitary response to LH-RH for LH release occurred during the follicular phase. The first peak of LH was well-correlated with the peak of plasma LH-RH but the later elevations of LH (observed within 90 to 150 minutes after LH-RH injection) were not necessarily related to the plasma level of immunoassayable LH-RH. Elevation of plasma levels of estrogen and progestin was observed wtihin 45 minutes after LH-RH injection. In saline control, the plasma level of LH was not elevated; however, plasma levels of estrogen and progestin were increased within 45 minutes after saline injection. Later elevation of plasma LH observed between 90 and 150 minutes after LH-RH injection may be due to administered LH-RH in cooperation with elevated levels of plasma estrogen and progestin. To pursue this problem, injections of estrogen and/or progesterone were performed during the early follicular phase. Injection of 600 mug of estrodiol benzoate (EB) for 3 days caused an elevation of plasma level of LH and enhanced pituitary LH responsiveness to LH-RH for LH release; however, injection of 100 mug EB for 3 days showed less effect on LH release. Injection of 10 mg of progesterone for 3 days also caused an elevation of plasma level of LH and enhanced the pituitary responsiveness to LH-RH release. Injection of both 600 mug EB and 10 mg progesterone for 3 days did not elevate plasma level of LH and showed no significant effect of LH-RH on LH release as compared to control. These results suggest that elevated levels of circulating estrogen and progestin may determine LH release and exposure of the pituitary to LH-RH is necessary for LH release. In dose and time schedule used in this study, it is inferred that estrogen and progesterone may exert their direct effect to hypothalamus on endogenous LH-RH secretion and also may exert their effect on pituitary gonadotrophs to change the sensitivity to LH-RH, i.e. these steroid hormones may be major factors in the control of gonadotropin release in the baboon. In a 2-part study, 15 female baboons were injected with 100 mcg luteinizing hormone-releasing hormone (LH-RH) sc in the early follicular and early luteal phases to examine the mechanism of LH release. Assays of blood samples after the luteal-phase injection showed a peak plasma level of LH-RH at 4 minutes with a sharp then slow decline. LH peaked within 30 minutes and again at 90 and 150 minutes, the latter 2 peaks not apparently related to the LH-RH injection. There was a lesser LH release after the follicular-phase injection. Since elevations of plasma estrogen and progestin were observed within 45 minutes in both treated animals and controls, it was hypothesized that the later LH peaks might be due to enhancement of the response to LH-RH by the estrogen and progestin. Injections of 600 mcg estradiol benzoate or 10 mg progesterone for 3 days enhanced pituitary LH responsiveness, but the injection of both together showed no significant effect. It is suggested that estrogen and progesterone may exert both a direct effect on the hypothalamus to control LH-RH secretion and an effect on the pituitary gonadotropins to alter the sensitivity to this LH-RH secretion.
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