Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells.
Article Details
- CitationCopy to clipboard
Chen JJ, Wang PS, Chien EJ, Wang SW
Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells.
Br J Pharmacol. 2001 Apr;132(8):1761-8.
- PubMed ID
- 11309248 [ View in PubMed]
- Abstract
Digoxin (10(-7) - 10(-5) M) or digitoxin (10(-7) - 10(-5) M) decreased the basal and human chorionic gonadotropin (hCG)-stimulated release of progesterone from rat granulosa cells. Digoxin (10(-5) M) or digitoxin (10(-5) M) attenuated the stimulatory effects of forskolin and 8-bromo-cyclic 3' : 5'-adenosine monophosphate (8-Br-cAMP) on progesterone release from rat granulosa cells. Digoxin (10(-5) M) or digitoxin (10(-5) M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450(scc)) activity (conversion of 25-hydroxyl cholesterol to pregnenolone) in rat granulosa cells but did not influence the activity of 3beta-hydroxysteroid dehydrogenase (3beta-HSD). Neither progesterone production nor P450scc activity in rat granulosa cells was altered by the administration of ouabain. Digoxin (10(-5) M) or digitoxin (10(-5) M), but not ouabain, decreased the expression of P450scc and steroidogenic acute regulatory (StAR) protein in rat granulosa cells. The present results suggest that digoxin and digitoxin decrease the progesterone release by granulosa cells via a Na(+),K(+)-ATPase-independent mechanism involving the inhibition of post-cyclic AMP pathway, cytochrome P450scc and StAR protein functions.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Digitoxin Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans YesInhibitorDetails Digoxin Sodium/potassium-transporting ATPase subunit alpha-1 Protein Humans YesInhibitorDetails - Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Digoxin Cholesterol side-chain cleavage enzyme, mitochondrial Protein Humans UnknownInhibitorDetails