Effect of adrenocorticotropin stimulation on the synthesis of 19-noraldosterone in man.
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.
Takeda
Y
Y
Second Department of Internal Medicine, Kanazawa University School of Medicine, Japan.
Miyamori
I
I
Yoneda
T
T
Furukawa
K
K
Hatakeyama
H
H
Inaba
S
S
Ito
Y
Y
Takeda
R
R
Mabuchi
H
H
D015069:18-Hydroxycorticosterone / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000450:Aldosterone / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism / Q000652:urine; D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D008875:Middle Aged; D015384:Zona Glomerulosa / Q000378:metabolism
D000804:Angiotensin II; C051358:18-hydroxy-19-norcorticosterone; C051957:18,19-dihydroxycorticosterone; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; C027514:19-noraldosterone; D000324:Adrenocorticotropic Hormone