Angiotensin II and III metabolism and effects on steroid production in the HAC15 human adrenocortical cell line

Endocrinology. 2013 Jan;154(1):214-21. doi: 10.1210/en.2012-1557. Epub 2012 Dec 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 3-Hydroxysteroid Dehydrogenases / genetics
  • Adrenal Cortex / drug effects
  • Adrenal Cortex / metabolism
  • Aldosterone / metabolism
  • Angiotensin II / metabolism*
  • Angiotensin II / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology
  • Angiotensin III / metabolism*
  • Angiotensin III / pharmacology*
  • Cell Line
  • Cytochrome P-450 CYP11B2 / genetics
  • Humans
  • Hydrocortisone / metabolism
  • Losartan / pharmacology
  • Steroid 11-beta-Hydroxylase / genetics
  • Steroid 17-alpha-Hydroxylase / genetics

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin II
  • Angiotensin III
  • Aldosterone
  • 3-Hydroxysteroid Dehydrogenases
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase
  • Losartan
  • Hydrocortisone