佛波酯抑制大鼠颗粒细胞中促黄体生成素刺激孕酮产生的机制。

The mechanisms by which phorbol ester inhibits LH stimulation of progesterone production in rat granulosa cells.

作者信息

Kawai Y, Clark M R

出版信息

Endocr Res. 1986;12(3):211-28. doi: 10.1080/07435808609035438.

Abstract

Tumor-promoting phorbol esters are believed to affect cell functions by activating a Ca+2-and lipid-dependent protein kinase (protein kinase C). 12-0-Tetradecanoyl phorbol-13-acetate (TPA) inhibits LH stimulation of progesterone (P) accumulation in rat granulosa cells. To determine the mechanisms by which TPA inhibits LH stimulation of P accumulation, TPA regulation of various ovarian steroidogenic enzymes was investigated. Cells were obtained from immature (28-29 days old) rats 48 h after injection of 20 IU PMSG and incubated for up to 5 h. TPA decreased the P responses to LH, cholera toxin, and (Bu)2cAMP by 20%, 24%, and 28%, respectively. One locus of inhibition of LH action, therefore, was after cAMP. TPA decreased LH-stimulated 3-beta-hydroxysteroid dehydrogenase activity. Furthermore, TPA stimulated 20-alpha-hydroxysteroid dehydrogenase activity. The combination of TPA and A23187 inhibited LH-stimulated P accumulation to the same extent as TPA alone. These data suggest that TPA-induced decreases in LH-stimulated P production result from both the inhibition of P biosynthesis and the stimulation of P breakdown.

摘要

促肿瘤佛波酯被认为通过激活一种钙和脂质依赖性蛋白激酶（蛋白激酶C）来影响细胞功能。12-0-十四酰佛波醇-13-乙酸酯（TPA）抑制大鼠颗粒细胞中促黄体生成素（LH）刺激的孕酮（P）积累。为了确定TPA抑制LH刺激P积累的机制，研究了TPA对各种卵巢类固醇生成酶的调节作用。从注射20 IU孕马血清促性腺激素（PMSG）48小时后的未成熟（28 - 29日龄）大鼠中获取细胞，并培养长达5小时。TPA分别使P对LH、霍乱毒素和双丁酰环磷腺苷（dBcAMP）的反应降低了20%、24%和28%。因此，LH作用的一个抑制位点在环磷腺苷（cAMP）之后。TPA降低了LH刺激的3-β-羟基类固醇脱氢酶活性。此外，TPA刺激了20-α-羟基类固醇脱氢酶活性。TPA与A23187的组合对LH刺激的P积累的抑制程度与单独使用TPA相同。这些数据表明，TPA诱导的LH刺激的P产生减少是由于P生物合成的抑制和P分解的刺激共同作用的结果。