Direct effect of propylthiouracil on progesterone release in rat granulosa cells.
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.
Chen
Jiann-Jong
JJ
Department of Nursing, Cardinal Tien College of Nursing, Taipei 23148, Republic of China.
Wang
Shyi-Wu
SW
Chien
Eileen-Jea
EJ
Wang
Paulus S
PS
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
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