INHIBITION OF UTERINE CONTRACTILITY BY PROGESTERONE AND PROGESTERONE METABOLITES - MEDIATION BY PROGESTERONE AND GAMMA-AMINO BUTYRIC ACID(A) RECEPTOR SYSTEMS
INHIBITION OF UTERINE CONTRACTILITY BY PROGESTERONE AND PROGESTERONE METABOLITES - MEDIATION BY PROGESTERONE AND GAMMA-AMINO BUTYRIC ACID(A) RECEPTOR SYSTEMS
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DOI：
10.1095/biolreprod45.2.266
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发表时间：
1991-08-01
影响因子：
3.6
通讯作者：
MAHESH, VB
中科院分区：
文献类型：
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作者：
PUTNAM, CD;BRANN, DW;MAHESH, VB
孕酮和几种孕酮代谢物能够抑制子宫收缩力。 一些孕酮代谢物对孕酮受体表现出很小的亲和力或没有亲和力，但已发现它们是GABA（A）受体系统的有效调节剂。 本研究探讨孕酮及其代谢产物对子宫收缩的抑制作用是孕酮受体介导的还是γ-氨基丁酸（A）（GABA（A））受体介导的。 在固定张力为1克的条件下，测量了2号间情期大鼠5毫米长的子宫组织环的子宫收缩。试验的类固醇是3-β-羟基-5-β-葡聚糖-20-酮（6 μ g/ml）、5-β-胆甾烷-3，20-二酮（10 μ g/ml）、3-α-羟基-5-α-胆甾烷-20-酮（3-α，5-α-THP，27.5 μ g/ml）和孕酮（40 μ g/ml）。 与对照组相比，所有化合物均显著抑制自发性子宫收缩。 当单独给药时，16 μ g/ml孕酮拮抗剂RU 486或32 μ g/ml GABA（A）拮抗剂苦味酸毒素均未观察到作用。 然而，当子宫组织暴露于类固醇和拮抗剂的组合时，3-β-羟基-5-β-葡聚糖-20-酮和3-α，5-α-THP的作用被印防己毒素阻断，但不被RU 486阻断，表明这些类固醇的作用是通过GABA（A）系统介导的。 RU 486可有效阻断5-β-甾烷-3，20-二酮和孕酮的作用，但印防己毒素不能阻断，表明它们的作用是通过孕酮受体系统介导的。 这些结果表明，在子宫中存在多种机制，通过孕酮及其代谢产物抑制子宫收缩力。
Progesterone and several progesterone metabolites are capable of inhibiting uterine contractility. Some progesterone metabolites have shown little or no affinity for the progesterone receptor but have been found to be potent modulators of the GABA(A) receptor system. This study examined whether the inhibition of uterine contraction by progesterone and its metabolites was progesterone receptor-mediated or gamma amino butyric acid(A) (GABA(A)) receptor-mediated. Uterine contractions were measured in annular rings of uterine tissue, 5 mm in length, from diestrous II rats, under a fixed tension of 1 gram. The steroids tested were 3-beta-hydroxy-5-beta-pregnan-20-one (6-mu-g/ml), 5-beta-pregnane-3,20-dione (10-mu-g/ml), 3-alpha-hydroxy-5-alpha-pregnan-20-one (3-alpha,5-alpha-THP, 27.5-mu-g/ml), and progesterone (40-mu-g/ml). All compounds significantly inhibited spontaneous uterine contractions when compared to controls. No effect was seen by either 16-mu-g/ml of the progesterone antagonist, RU486, or 32-mu-g/ml of the GABA(A) antagonist, pictrotoxin, when administered alone. However, when uterine tissues were exposed to a combination of the steroid and the antagonist, the effect of 3-beta-hydroxy-5-beta-pregnan-20-one and 3-alpha,5-alpha-THP was blocked by picrotoxin but not by RU486, indicating that the action of these steroids was mediated through the GABA(A) system. The effect of 5-beta-pregnane-3,20-dione and progesterone was effectively blocked by RU486 but not by picrotoxin, suggesting that their actions were mediated through the progesterone receptor system. These results indicate that multiple mechanisms exist in the uterus for inhibiting uterine contractility by progesterone and its metabolites.