Steroid biosynthesis is initiated with transportation of
cholesterol along with
steroidogenic acute regulatory protein (StAR) into the mitchondria and is achieved with several steroidogenic
enzymes. It has been reported that Ca(2+) channel blockers (CCBs), such as
azelnidipine,
efonidipine and
nifedipine, suppress the biosynthesis of
aldosterone and
cortisol, but the overall effects of CCBs on
steroid biosynthesis remain to be clarified. The present study was designed to evaluate the effects of CCBs on the expression of steroidogenic
enzymes and the production of adrenal
androgen,
dehydroepiandrosterone sulfate (
DHEA-S) that has anti-atherosclerotic actions. NCI-H295R human
adrenocortical carcinoma cells and HepG2 human
hepatoma cells were cultured for 24 hours with or without a CCB (
amlodipine,
efonidipine,
nifedipine,
azelnidipine R(-)-
efonidipine,
verapamil or
diltiazem). HepG2
hepatoma cells were used to confirm the effects of CCBs on the expression of StAR. In fact,
efonidipine and
nifedipine increased the expression of StAR in HepG2 cells.
Efonidipine and
nifedipine, but not other examined CCBs, also increased the N(6), 2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (
dbcAMP)-induced StAR
mRNA, which reflects the action of
adrenocorticotropic hormone, and
efonidipine and R(-)-
efonidipine enhanced the
dbcAMP-induced
DHEA-S production in NCI-H295R
adrenocortical carcinoma cells. Therefore,
efonidipine and
nifedipine might increase the expression of StAR and, in turn,
efonidipine enhanced the
dbcAMP-induced
DHEA-S production, independent of Ca(2+) channel blockade. These results indicate that such effects are not associated with Ca(2+) influx. Moreover, only
efonidipine enhanced the
angiotensin II-induced expression of StAR
mRNA (P < 0.01 vs.
angiotensin II alone). In conclusion,
efonidipine might exert an additional action beyond
anti-hypertensive actions.