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Research on the Control Mechanism of the Secretion of Ovarian Steroid Hormones

卵巢类固醇激素分泌控制机制的研究

基本信息

批准号：
63570799
负责人：
ARAI Kiyoshi
金额：
$ 1.47万
依托单位：
Teikyo University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1990
项目状态：
已结题

项目摘要

1) The gonadotropin secretion from the rat anterior pituitary was suppressed by progestin. RU486 (anti progestin drug) inhibited this suppression. We confirmed this both in vivo and in vitro. Desogestrel (DG) had no effect by itself, but 3 keto-DG (the metabolite of DG) decre ased the gonadotropin rease.2) We investigated the effect of synthetic steroids on ovarian enzymes. In conclusion, 3beta-HSD was inhibited by gestrinone, 3 keto-DG and 17,20 lyase was inhibited by danazol and DG. This experiment indicated that DG inhibited the synthesis of ovarian steroids directy.3) There is an EGF receptor in the ovary of pregnant rat. We cocultured luteal cells with EGF for two days and EGF counteracted the tropic effect of gonadotropins without any effect on basal levels of P_4, 20alpha-OH-P_4 and cAMP.4) There are receptors of insulin and IGFs in the ovary of pregnant rats. We cultured luteal cells with insulin or IGFs. When IBMX was used with these peptides, they increased the levels of P_4, 20alpha-OH-P_4 and cAMP. Without IBMX, these peptides had little effect because they stimu lated the activity of cAMP phosphodiesterase.5) RU486 had luteolytic effect on cultured luteal cells, but it had a weak effect on serum P_4 level of the hypophysectomized PMS-hCG treated rat. Therefore the strong luteolytic effect of RU486 observed in vivo was exerted mainly through the pituitary.

1)孕激素抑制大鼠垂体前叶的促性腺激素分泌。 RU486（抗孕激素药物）可以抑制这种抑制。我们在体内和体外都证实了这一点。去氧孕烯(DG)本身没有作用，但3酮-DG(DG的代谢物)可降低促性腺激素的释放。2)我们研究了合成类固醇对卵巢酶的影响。总之，3β-HSD 被孕三烯酮抑制，3 酮-DG 被抑制，17,20 裂解酶被达那唑和 DG 抑制。本实验表明DG直接抑制卵巢类固醇的合成。3)妊娠大鼠卵巢中存在EGF受体。我们将黄体细胞与EGF共培养两天，EGF抵消了促性腺激素的促性作用，但对P_4、20α-OH-P_4和cAMP的基础水平没有任何影响。4）妊娠大鼠的卵巢中存在胰岛素和IGF受体。我们用胰岛素或 IGF 培养黄体细胞。当 IBMX 与这些肽一起使用时，它们增加了 P_4、20α-OH-P_4 和 cAMP 的水平。如果没有IBMX，这些肽几乎没有作用，因为它们刺激cAMP磷酸二酯酶的活性。5)RU486对培养的黄体细胞具有溶黄体作用，但对垂体切除的PMS-hCG处理的大鼠的血清P_4水平作用较弱。因此，体内观察到的RU486的强黄体分解作用主要是通过垂体发挥的。