Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Endocrine. 2010 Feb;37(1):187-93. doi: 10.1007/s12020-009-9287-7. Epub 2009 Dec 15.
The objective of the study was to evaluate the effect of valproic acid (VPA) on ovarian androgen biosynthesis in primary cultures of theca-interstitial (T-I) cells isolated from rat ovaries. Ovarian T-I cells were cultured with VPA in the presence or absence of hCG. VPA did not increase basal or hCG-stimulated androgen synthesis when added to primary cultures of T-I cells. However, the addition of VPA caused a marked concentration-dependent inhibitory effect on hCG-stimulated androstendione synthesis. Treatment of T-I cells with 8-Bromo-cAMP resulted in a marked increase in the production of androstenedione, and VPA inhibited this stimulatory effect, suggesting that the mechanism of VPA's inhibitory effect on androstenedione production occurs at a step after second messenger activation. Treatment of T-I cells with hCG resulted in a significant increase in the mRNA expression of steroidogenic enzymes CYP17A1 and 17β-hydroxysteroid dehydrogenase. Addition of VPA sharply blunted the stimulatory effect of hCG, reducing the mRNA expression of the steroidogenic enzymes to basal levels. In conclusion, VPA exerts an inhibitory effect on hCG-stimulated androgen synthesis in rat T-I cells.
本研究旨在评估丙戊酸（VPA）对大鼠卵巢间质-间质（T-I）细胞原代培养中卵巢雄激素生物合成的影响。在存在或不存在 hCG 的情况下，将卵巢 T-I 细胞与 VPA 一起培养。当添加到 T-I 细胞的原代培养物中时，VPA 不会增加基础或 hCG 刺激的雄激素合成。然而，VPA 的添加对 hCG 刺激的雄烯二酮合成表现出明显的浓度依赖性抑制作用。用 8-Bromo-cAMP 处理 T-I 细胞会导致雄烯二酮的产生明显增加，而 VPA 抑制这种刺激作用，表明 VPA 对雄烯二酮产生的抑制作用发生在第二信使激活后的一个步骤。用 hCG 处理 T-I 细胞会导致类固醇生成酶 CYP17A1 和 17β-羟甾体脱氢酶的 mRNA 表达显著增加。添加 VPA 会明显削弱 hCG 的刺激作用，将类固醇生成酶的 mRNA 表达降低到基础水平。总之，VPA 对大鼠 T-I 细胞中 hCG 刺激的雄激素合成具有抑制作用。
