title: Angiotensin II and III metabolism and effects on steroid production in the HAC15 human adrenocortical cell line.
abstract: 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.
authors.affiliation: Research and Medicine Services, Montgomery Veterans Affairs Medical Center, 1500 East Woodrow Wilson Drive, Jackson, MS 39216, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Oki
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Kopf
authors.forename: William B
authors.initials: WB
authors.lastname: Campbell
authors.forename: Milay
authors.initials: M
authors.lastname: Luis Lam
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Celso E
authors.initials: CE
authors.lastname: Gomez-Sanchez
authors.forename: Elise P
authors.initials: EP
authors.lastname: Gomez-Sanchez
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism* / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000805:Angiotensin III / Q000378:metabolism* / Q000494:pharmacology*; D002460:Cell Line; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000804:Angiotensin II; D000805:Angiotensin III; D000450:Aldosterone; D015096:3-Hydroxysteroid Dehydrogenases; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D019808:Losartan; D006854:Hydrocortisone