Premium
Direct inhibitory effect of digitalis on progesterone release from rat granulosa cells
Author(s) -
Chen JiannJong,
Wang Paulus S,
Chien EileenJea,
Wang ShyiWu
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703974
Subject(s) - digitoxin , medicine , endocrinology , cholesterol side chain cleavage enzyme , ouabain , quinidine , corpus luteum , digoxin , granulosa cell , luteal phase , chemistry , pregnenolone , forskolin , steroidogenic acute regulatory protein , human chorionic gonadotropin , cytochrome p450 , biology , metabolism , ovary , steroid , stimulation , biochemistry , gene expression , follicular phase , hormone , heart failure , organic chemistry , gene , sodium
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 3β‐hydroxysteroid dehydrogenase (3β‐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.British Journal of Pharmacology (2001) 132 , 1761–1768; doi: 10.1038/sj.bjp.0703974