Inhibitory effect of valproic acid on ovarian androgen biosynthesis in rat theca-interstitial cells

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• 作者：Senait Fisseha (1) (2)
  Roberto Towns (1) (2)
  Miyuki Harada (1) (2)
  Helle Peegel (1) (2)
  K. M. J. Menon (1) (2) (3)
  
• 关键词：Theca ; interstitial cells ; Androgen synthesis ; hCG ; Steroidogenesis ; Androstenedione ; Valproic acid ; PCOS
• 刊名：Endocrine
• 出版年：2010
• 出版时间：February 2010
• 年：2010
• 卷：37
• 期：1
• 页码：187-193
• 全文大小：340KB
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• 作者单位：Senait Fisseha (1) (2)
  Roberto Towns (1) (2)
  Miyuki Harada (1) (2)
  Helle Peegel (1) (2)
  K. M. J. Menon (1) (2) (3)
  
  1. Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
  2. Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, 48109, USA
  3. University of Michigan Medical School, 6428, Medical Science I, 1150 W. Medical Center Drive, Ann Arbor, MI, 48109, USA
  

文摘

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.