title: 11 beta-Hydroxylase activity in glucocorticoid suppressible hyperaldosteronism: lessons for essential hypertension?
abstract: Corticosteroid 11 beta-hydroxylation is catalysed by 11 beta-hydroxylase and aldosterone synthase. Using plasma steroid ratios, the level of this process in patients with glucocorticoid-suppressible hyperaldosteronism (GSH) was compared with that in unaffected control subjects and in patients with Conn's syndrome. Based on both 11-deoxycortisol:cortisol (S:F) and 11-deoxycorticosterone:corticosterone (DOC:B) ratios, patients with GSH showed impaired resting 11 beta-hydroxylase activity. In GSH, but not in the other groups, the S:F ratio was significantly correlated with basal plasma aldosterone concentration. ACTH infusion increased the S:F ratio in all these patient groups, suggesting a common partial deficiency. The results also indicate that 11 beta-hydroxylation may be rate-limiting in normal subjects. In control subjects and patients with Conn's syndrome, the DOC:B ratio was not affected by ACTH. However, in GSH patients, this ratio fell markedly, indicating an increased efficiency of 11 beta-hydroxylation of DOC (but not S). This may be due to the activation by ACTH of the zona fasciculata chimaeric aldosterone synthase characteristic of this disease. Plasma aldosterone, corticosterone and DOC concentrations, appeared to be more sensitive to ACTH in GSH than the other groups. The defect in 11 beta-hydroxylation in GSH accounts for the increased levels of DOC reported in the condition, and may contribute to the phenotypic variability.
authors.affiliation: Medical Research Council Blood Pressure Group, Therapeutics Western Infirmary, Glasgow, Scotland.
authors.forename: J M
authors.initials: JM
authors.lastname: Connell
authors.forename: A J
authors.initials: AJ
authors.lastname: Jamieson
authors.forename: E
authors.initials: E
authors.lastname: Davies
authors.forename: M
authors.initials: M
authors.lastname: Ingram
authors.forename: A
authors.initials: A
authors.lastname: Soro
authors.forename: R
authors.initials: R
authors.lastname: Fraser
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D002678:Chimera; D003345:Corticosterone / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D003900:Desoxycorticosterone / Q000097:blood; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006929:Hyperaldosteronism / Q000097:blood / Q000188:drug therapy / Q000201:enzymology*; D006973:Hypertension / Q000201:enzymology*; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D015383:Zona Fasciculata / Q000201:enzymology
chemical_list: D005938:Glucocorticoids; D003900:Desoxycorticosterone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase; D003345:Corticosterone; D003350:Cortodoxone; D006854:Hydrocortisone