Effect of activin A on dehydroepiandrosterone and testosterone secretion by primary immature porcine Leydig cells.
Effect of activin A on dehydroepiandrosterone and testosterone secretion by primary immature porcine Leydig cells.
复制标题
激活素 A 对原代未成熟猪 Leydig 细胞脱氢表雄酮和睾酮分泌的影响。
作者：
C. Mauduit;M. Chauvin;E. de Peretti;A. Morera;M. Benahmed
在本研究中，我们评估了同二聚体激活素A对原代培养的未成熟猪Leydig细胞功能的影响。激活素A（0.5-100 ng/ml）以剂量和时间依赖性方式减少hCG刺激的脱氢表雄酮（DHEA）蓄积，在20 ng/ml（8 x 10（-10）M）时具有最大抑制作用（减少58%）。激活素A被发现不控制类固醇生成，无论是通过调节促性腺激素LH/hCG结合或低密度脂蛋白胆固醇结合和内化。然而，激活素A显著降低了双烯醇酮，（p <0.002）和DHEA（p小于0.001）形成（在存在10（-5）M WIN 24540（3 β-羟基类固醇脱氢酶/异构酶[3 β-HSDI]活性抑制剂）的情况下进行评价）（3 ng/ml，3 h）或在22 R-羟基胆固醇存在下孵育（5 μ g/ml，2 h）。这些结果表明，激活素A可能对胆固醇侧链裂解细胞色素P450（P450 SCC）活性产生部分抑制作用。另一方面，激活素A显著（p小于0.001）增强了外源性双烯醇酮和DHEA（500 ng/ml）转化为睾酮，但不增强孕酮和雄烯二酮（500 ng/ml）转化为睾酮，表明激活素A潜在地增强了Leydig细胞中的3 β-HSDI活性。发现激活素A对3 β-HSDI活性的作用与转化生长因子-β 1（TGF β 1）的作用密切相关，因为激活素A（20 ng/ml）和TGF β 1（2 ng/ml）均诱导3 β-HSDI活性的相当的和非累加的增加。（250字处删节）
In the present study, we evaluated the effect of the homodimer activin A on immature porcine Leydig cell functions in primary culture. Activin A (0.5-100 ng/ml) reduced hCG-stimulated dehydroepiandrosterone (DHEA) accumulation in a dose- and time-dependent manner, with a maximal inhibitory effect (58% decrease) at 20 ng/ml (8 x 10(-10) M). Activin A was found not to control steroidogenesis, either through a modulation of the gonadotropin LH/hCG binding or low-density lipoprotein cholesterol binding and internalization. However, activin A significantly decreased pregnenolone (p less than 0.002) and DHEA (p less than 0.001) formation (evaluated in the presence of 10(-5) M of WIN 24540, an inhibitor of 3 beta-hydroxysteroid dehydrogenase/isomerase [3 beta-HSDI]activity) in Leydig cells maximally stimulated with hCG (3 ng/ml, 3 h) or incubated in the presence of 22R-hydroxycholesterol (5 micrograms/ml, 2 h). These findings indicate that activin A probably exerts a partial inhibitory effect on cholesterol side-chain cleavage cytochrome P450 (P450scc) activity. On the other hand, activin A significantly (p less than 0.001) enhanced the conversion of exogenous pregnenolone and DHEA (500 ng/ml) but not of progesterone and androstenedione (500 ng/ml) into testosterone, suggesting that activin A potentially enhances 3 beta-HSDI activity in Leydig cells. Activin A action on 3 beta-HSDI activity was found to be closely related to that of transforming growth factor-beta 1 (TGF beta 1), since both activin A (20 ng/ml) and TGF beta 1 (2 ng/ml) induced a comparable and non-additive increase in 3 beta-HSDI activity.(ABSTRACT TRUNCATED AT 250 WORDS)