Effect of adrenocorticotropin stimulation on the synthesis of 19-noraldosterone in man.

ABSTRACT

The hormone, 19-noraldosterone, which was recently shown to be synthesized and produced in the human adrenal gland, exhibits potent mineralocorticoid and hypertensinogenic activities. This hormone is controlled in part by the renin-angiotensin system. We studied the effects of ACTH stimulation on the synthesis of 19-noraldosterone in vitro and in six normal men. 19-Noraldosterone was measured by a specific RIA after the urine extract or incubation medium was purified by high performance liquid chromatography. The 24-h urinary excretion of 19-noraldosterone increased approximately 4-fold during the administration of ACTH (40 U, injected im twice daily for 3 days). Virtually identical responses were observed with aldosterone, 18-hydroxycorticosterone, 18,19-dihydroxycorticosterone, and 18-hydroxy-19-norcorticosterone. Glomerulosa cells isolated from human adrenals were incubated with angiotensin II (10(-7), 10(-8), and 10(-9) mol/L) or ACTH (10(-8), 10(-9), and 10(-10) mol/L). Angiotensin II and ACTH increased the production of 19-noraldosterone dose-dependently from isolated glomerulosa cells. The secretion of aldosterone, 18-hydroxycorticosterone, 18,19-dihydroxycorticosterone, and 18-hydroxy-19-norcorticosterone in response to angiotensin II and ACTH was identical to that of 19-noraldosterone. These observations suggest that 19-noraldosterone is stimulated by the renin-angiotensin system as well as ACTH.