Angiotensin II and III metabolism and effects on steroid production in the HAC15 human adrenocortical cell line. Endocrinology 2013 Jan;154(1):214-21
Date
12/12/2012Pubmed ID
23221601Pubmed Central ID
PMC3529373DOI
10.1210/en.2012-1557Scopus ID
2-s2.0-84871708442 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
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.
Author List
Oki K, Kopf PG, Campbell WB, Luis Lam M, Yamazaki T, Gomez-Sanchez CE, Gomez-Sanchez EPAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
3-Hydroxysteroid DehydrogenasesAdrenal Cortex
Aldosterone
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Angiotensin III
Cell Line
Cytochrome P-450 CYP11B2
Humans
Hydrocortisone
Losartan
Steroid 11-beta-Hydroxylase
Steroid 17-alpha-Hydroxylase