title: Direct effect of propylthiouracil on progesterone release in rat granulosa cells.
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 3beta-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.
authors.affiliation: Department of Nursing, Cardinal Tien College of Nursing, Taipei 23148, Republic of China.
authors.forename: Jiann-Jong
authors.initials: JJ
authors.lastname: Chen
authors.forename: Shyi-Wu
authors.initials: SW
authors.lastname: Wang
authors.forename: Eileen-Jea
authors.initials: EJ
authors.lastname: Chien
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D015153:Blotting, Western; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis; D011374:Progesterone / Q000378:metabolism*; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D013956:Antithyroid Agents; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D000001:Calcimycin; D011374:Progesterone; D008713:Methimazole; D011441:Propylthiouracil; D003577:Cytochrome P-450 Enzyme System; D015096:3-Hydroxysteroid Dehydrogenases; D002118:Calcium