The expression of steroidogenic enzyme genes in human vascular cells.
Recently, we demonstrated that aldosterone is produced by human vascular cells, and that vascular aldosterone is linked to angiotensin II-induced hypertrophy of vascular smooth muscle cells. We therefore examined whether genes encoding steroidogenic enzymes responsible for aldosterone biosynthesis from cholesterol are expressed in vascular cells. Using polymerase chain reaction after reverse transcription, type I and II 3 beta-HSD (3 beta-hydroxysteroid dehydrogenase), P-450c21 (21-hydroxylase), and P-450c18 (18-hydroxylase/oxidase) genes were found to be expressed both in endothelial cells and smooth muscle cells cultivated from human pulmonary arteries. However, P-450scc (cholesterol side chain cleavage enzyme) and P-45011 beta (11 beta-hydroxylase) mRNAs could not be detected. These findings suggest that the enzyme system responsible for aldosterone production in human vascular cells is different from that found in the adrenal cortex and that vascular aldosterone may be synthesized from metabolic intermediates which originate from the circulation. Extra-adrenal 3 beta-HSD and steroid 21-hydroxylase occur in a wide variety of tissues. Thus, human vascular cells can retain the ability to produce aldosterone by expressing the P-450c18 gene.
Second Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
H
H
Hatakeyama
I
I
Miyamori
Y
Y
Takeda
H
H
Yamamoto
H
H
Mabuchi
D015096:3-Hydroxysteroid Dehydrogenases / Q000187:drug effects / Q000235:genetics*; D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D013255:Steroid 21-Hydroxylase
D012333:RNA, Messenger; D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003577:Cytochrome P-450 Enzyme System; D015096:3-Hydroxysteroid Dehydrogenases; D013255:Steroid 21-Hydroxylase