Asif AR, Ljubojevic M, Sabolic I, Shnitsar V, Metten M, Anzai N,
Mueller GA, Burckhardt G, Hagos Y.Regulation of steroid
hormone biosynthesis enzymes and organic anion transporters by
forskolin and DHEAS treatment in adrenocortical cells.
Am J Physiol Endocrinol Metab. 2006 Jul 11
Department of Nephrology, Universität Göttingen,
Humboldtallee 23, 37073 Goettingen, Germany.
Several important physiological functions are regulated by
cortisol. Previously, we demonstrated the involvement of human
organic anion transporter 3 (hOAT3) in cortisol release. In the
present study, we investigated the influence of
dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate on
cortisol release in a human adrenocortical cell line (NCI-H295R)
compared with forskolin stimulation. Additionally, we examined
the impact of forskolin and DHEA-S on the expression of key
enzymes in steroid biosynthesis and expression of hOAT3 and -4
in NCI-H295R cells. The cortisol release was increased 10-fold
after 24-h incubation with DHEA-S, but incubation with estrone
sulfate did not show any significant change in cortisol release.
When cells were incubated with DHEA-S in the presence of
forskolin, an additive influence of DHEA-S stimulation of
cortisol was recorded over forskolin alone. The 24-h stimulation
of NCI-H295R cells with forskolin increased the expression of
steroidogenic acute regulatory protein (StAR), CYP17, CYP21A2,
and CYP11A1, whereas only StAR mRNA expression was increased
significantly by incubation with DHEA-S. Immunofluorescence
analyses revealed strongly elevated expression of hOAT3 by
forskolin as well as by DHEA-S stimulation. We conclude that the
increased cortisol release of adrenocortical cells by DHEA-S and
forskolin stimulation is probably due to high expression of the
key enzymes of steroid biosynthesis and hOAT3.
PMID: 16835396 [
|
