丙硫氧嘧啶对大鼠颗粒细胞孕酮释放的直接作用。

Direct effect of propylthiouracil on progesterone release in rat granulosa cells.

Chen Jiann-Jong, Wang Shyi-Wu, Chien Eileen-Jea, Wang Paulus S

Department of Nursing, Cardinal Tien College of Nursing, Taipei 23148, Republic of China.

Br J Pharmacol. 2003 Aug;139(8):1564-70. doi: 10.1038/sj.bjp.0705392.

Abstract

The present study was to investigate the direct effect and action mechanism of propylthiouracil (PTU), an antithyroid drug, on the production of progesterone in rat granulosa cells. 2. PTU (3-12 mM) decreased the basal and human chorionic gonadotropin (hCG)-stimulated release of progesterone from rat granulosa cells. 3. PTU (3-12 mM) attenuated the stimulatory effects of forskolin and 8-bromo-cyclic 3':5'-adenosine monophosphate on progesterone release from rat granulosa cells. 4. PTU (12 mM) inhibited the activities of both the cytochrome P450 side-chain cleavage enzyme (P450scc, conversion of 25-hydroxyl cholesterol to pregnenolone) and the 3beta-hydroxysteroid dehydrogenase (conversion of pregnenolone to progesterone) in rat granulosa cells. PTU decreased the V(max) but increased the K(m) of P450scc. 5. PTU (12 mM) decreased the hCG-increased amount of steroidogenic acute regulatory (StAR) protein in rat granulosa cells. 6. The present results suggest that PTU decreases the progesterone release by granulosa cells via a thyroid-independent mechanism involving the inhibition of post-cAMP pathway, and the activities of intracellular calcium, steroidogenic enzyme, and StAR protein functions.

摘要

本研究旨在探讨抗甲状腺药物丙硫氧嘧啶（PTU）对大鼠颗粒细胞孕酮生成的直接作用及其作用机制。2. PTU（3 - 12 mM）可降低大鼠颗粒细胞基础状态下以及人绒毛膜促性腺激素（hCG）刺激下的孕酮释放。3. PTU（3 - 12 mM）可减弱福斯高林和8 - 溴环磷酸腺苷对大鼠颗粒细胞孕酮释放的刺激作用。4. PTU（12 mM）可抑制大鼠颗粒细胞中细胞色素P450侧链裂解酶（P450scc，将25 - 羟基胆固醇转化为孕烯醇酮）和3β - 羟基类固醇脱氢酶（将孕烯醇酮转化为孕酮）的活性。PTU降低了P450scc的V(max)但增加了其K(m)。5. PTU（12 mM）可降低大鼠颗粒细胞中hCG增加的类固醇生成急性调节蛋白（StAR）的量。6. 目前的结果表明，PTU通过一种不依赖甲状腺的机制降低颗粒细胞孕酮释放，该机制涉及抑制cAMP下游途径以及细胞内钙、类固醇生成酶和StAR蛋白功能。