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This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/E1351    most recent 00653.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Asif, A. R. Articles by Hagos, Y. Search for Related Content PubMed PubMed Citation Articles by Asif, A. R. Articles by Hagos, Y.

Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells

Departments of ¹Nephrology and Rheumatology, ²Clinical and Experimental Endocrinology, and ³Vegetative Physiology and Pathophysiology, Universität Göttingen, Gottingen, Germany; ⁴Unit of Molecular Toxicology, Institute for Medical Research and Occupational Health, Zagreb, Croatia; and ⁵Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan

Submitted 29 December 2005 ; accepted in final form 29 June 2006

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.

cortisol; NCI-H295R cells; organic anion transporter 3; organic anion transporter 4; adrenal gland; human adrenocortical cells; SLC22A8; SLC22A11; forskolin; dehydroepiandrosterone sulfate