Direct effect of propylthiouracil on progesterone release in rat granulosa cells

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

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

Abstract

1. 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 3β-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.

Original languageEnglish
Pages (from-to)1564-1570
Number of pages7
JournalBritish Journal of Pharmacology
Volume139
Issue number8
DOIs
StatePublished - 08 2003

Keywords

  • 3β-HSD activity
  • Calcium
  • Granulosa cells
  • P450scc activity
  • Progesterone
  • Propylthiouracil
  • StAR expression
  • Toxicology

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