Assessment of 11beta-hydroxylase activity with plasma corticosterone, deoxycorticosterone, cortisol, and deoxycortisol: role of ACTH and angiotensin.
In this study we evaluated the role of ACTH and angiotensin on regulation of activities of 11beta-hydroxylases of the adrenal cortex. The ratio of the plasma concentrations of 11 deoxycorticosterone (DOC) to plasma corticosterone (B) reflected the activity of the enzyme of the B and/or aldosterone pathways, and the ratio of plasma 11-deoxycortisol (S) to plasma cortisol (F) as the activity of the enzyme in the F pathway. In normal subjects, both ratios were significantly lower at 0800-0900 h (Doc to B, .01+/-.004, mean+/-SE, n=10; and S to F, .01+/-.003) than at 2000 h (DOC to B, .028+/-.024 and S to F, .015+/-.005). The plasma levels of DOC, B, S and F were all significantly lower at 2000-2100 h than at 0800-0900 h. In contrast 9 patients with Cushing's syndrome exhibited no diurnal change in the ratios. The ratios increased substantially following dexamethasone or metyrapone administration. A high or low salt diet and an angiotensin infusion produced no significant effect on the ratios. The plasma concentration of all four steroids was increased by more than 50% by an infusion of angiotensin. Four hours after administration of 80 mg of Lasix at 0800 h to 10 normal subjects, the ratios of DOC to B and S to F increased significantly (P less than .02), an effect possibly related to a decreased secretion of ACTH.


CONCLUSIONS
1) 11beta-hydroxylase activity of the B and/or aldosterone and F pathways appears to change in parallel with ACTH secretion, and 2) although angiotensin stimulates steroidogenesis of the pathways, it has no apparent effect on 11beta-hydroxylase activity.
D015065:17-Hydroxycorticosteroids / Q000097:blood*; D000302:Adrenal Cortex / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D002940:Circadian Rhythm; D003345:Corticosterone / Q000097:blood*; D003350:Cortodoxone / Q000097:blood*; D003480:Cushing Syndrome / Q000097:blood; D003900:Desoxycorticosterone / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D005665:Furosemide / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008797:Metyrapone / Q000494:pharmacology; D011187:Posture; D012083:Renin / Q000502:physiology; D013250:Steroid Hydroxylases / Q000378:metabolism*
D015065:17-Hydroxycorticosteroids; D000804:Angiotensin II; D003900:Desoxycorticosterone; D000450:Aldosterone; D005665:Furosemide; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D012083:Renin; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone; D008797:Metyrapone