Among the 15 steroids in the panel, 11-deoxycortisol and 11-deoxycorticosterone
were the only 2 that were consistently higher (P < 0.0001) in all subtypes ofCS than in groups without CS.
Knockdown of Dicer1 significantly increased secreted levels of cortisol (1.33 [+ or -] 0.11fold; p = 0.01), corticosterone (1.32 [+ or -] 0.13-fold; p = 0.03), 11-deoxycorticosterone
(1.53 [+ or -] 0.09-fold; p <0.001), 18- hydroxycorticosterone (1.29 [+ or -] 0.10-fold; p = 0.04), and aldosterone (1.47 [+ or -] 0.11-fold; p <0.01) relative to scrambled siRNA transfected cells.
Purified CYP11B2 catalyzed the multi-hydroxylation reactions of the substrate (11-deoxycorticosterone
) giving corticosterone, 18-hydroxydeoxycorticosterone, 18-hydroxycorticosterone, and significant amount of aldosterone as products, while purified CYP11B1 catalyzed only 11[beta]- and 18-hydroxylations of the same substrate to yield corticosterone and 18-hydroxydeoxycorticosterone, respectively (refer to Fig.
All core clinical biochemistry and hormonal tests were performed at Royal Hospital, Oman, using Architect 8000c and Architect 2000i, respectively, with Automated Processing System (Abbott, USA); and 17[alpha]-hydroxyprogesterone, renin and aldosterone were performed by ELISA (DRG, USA); while 11-deoxycortisol, 11-deoxycorticosterone
, corticosterone, androstenedione and ACTH were performed at Laboratoroire Cerba (France).
As measured by HPLC, corticosterone and 11-deoxycorticosterone
secretion to the medium increased linearly for at least 24 hr.
We have tentatively identified 11-deoxycorticosterone
, androstadienedione, and androstenedione in the effluent.
Androstenedione, cortisone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone
, pregnenolone, 17-hydroxyprogesterone, and 17-hydroxypregenenolone were from Steraloids.
Compared to normal female individuals, female carriers for 21-OHD frequently demonstrate an increased secretion of the 21-OH precursors 17-hydroxyprogesterone (17-OHP) and progesterone (P4) [35-43] and lower levels of 11-deoxycorticosterone
 as expected.
Beginning from 11-deoxycorticosterone
in the zona glomerulosa of the adrenal cortex, aldosterone synthase catalyzes the sequential activities of 11[beta]-hydroxylase, 18-hydroxylase, and, finally, 18-methyl oxidase, the final three steps in aldosterone synthesis (1,2).
We measured 15 adrenal steroids simultaneously by LCMS/MS, including aldosterone, cortisol, 18-oxocortisol, 18-hydroxycortisol, cortisone, 11-deoxycortisol, 21deoxycortisol, corticosterone, 11-deoxycorticosterone
, progesterone, 17-hydroxyprogesterone, pregnenolone, androstenedione, dehydroepiandrosterone (DHEA), and DHEA-sulfate (DHEA-S).
The accumulation of 11-deoxycorticosterone
and its metabolites causes hypertension in about two-thirds of these patients.
Deficiency of 21-hydroxylase prevents the conversion of 17-hydroxyprogesterone to 11-deoxycorticosterone
, leading to excessive production of androgens, which ultimately affects several stages of growth and development (4).