Angiotensin II and III Metabolism and Effects on Steroid Production in the HAC15 Human Adrenocortical Cell Line
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- Kenji Oki
- Research and Medicine Services (K.O., M.L.L., C.E.G.-S., E.P.G.-S.), University of Mississippi Medical Center, Jackson, Mississippi 39216
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- Phillip G. Kopf
- Department of Pharmacology and Toxicology (P.G.K., W.B.C.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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- William B. Campbell
- Department of Pharmacology and Toxicology (P.G.K., W.B.C.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226
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- Milay Luis Lam
- Research and Medicine Services (K.O., M.L.L., C.E.G.-S., E.P.G.-S.), University of Mississippi Medical Center, Jackson, Mississippi 39216
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- Takeshi Yamazaki
- Graduate School of Integrated Arts and Sciences (T.Y.), Hiroshima University, Higashi-Hiroshima 739-8521, Japan
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- Celso E. Gomez-Sanchez
- Research and Medicine Services (K.O., M.L.L., C.E.G.-S., E.P.G.-S.), University of Mississippi Medical Center, Jackson, Mississippi 39216
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- Elise P. Gomez-Sanchez
- Research and Medicine Services (K.O., M.L.L., C.E.G.-S., E.P.G.-S.), University of Mississippi Medical Center, Jackson, Mississippi 39216
Abstract
<jats:p>Aldosterone is synthesized in the zona glomerulosa of the adrenal cortex under primary regulation by the renin-angiotensin system. Angiotensin II (A-II) acts through the angiotensin types 1 and 2 receptors (AT1R and AT2R). A-II is metabolized in different tissues by various enzymes to generate two heptapeptides A-III and angiotensin 1-7, which can then be catabolized into smaller peptides. A-II was more potent than A-III in stimulating aldosterone secretion in the adrenocortical cell line HAC15, and A-II, but not A-III, stimulated cortisol secretion. A-II stimulated mRNA expression of steroidogenic acute regulatory protein, 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2, whereas A-III stimulated 3β-hydroxysteroid dehydrogenase, CYP11B1, and CYP11B2 but decreased the expression of CYP17A1 required for cortisol synthesis. The stimulation of aldosterone secretion by A-II and A-III was blocked by the AT1R receptor blocker, losartan, but not by an AT2R blocker. A-II was rapidly metabolized by the HAC15 cells to mainly to angiotensin 1-7, but not to A-III, and disappeared from the supernatant within 6 h. A-III was metabolized rapidly and disappeared within 1 h. In conclusion, A-II was not converted to A-III in the HAC15 cell and is the more potent stimulator of aldosterone secretion and cortisol of the two. A-III stimulated aldosterone secretion but not cortisol secretion.</jats:p>
Journal
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- Endocrinology
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Endocrinology 154 (1), 214-221, 2013-01-01
The Endocrine Society
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Keywords
Details 詳細情報について
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- CRID
- 1360848661868057088
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- ISSN
- 19457170
- 00137227
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- Data Source
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- Crossref
- KAKEN