title: Apparent double defect in C11 beta and C21-steroid hydroxylation in congenital adrenal hyperplasia.
abstract: Some patients with either fully developed, mild or even hidden forms of congenital adrenal hyperplasia have both 21-deoxycortisol and increased 11-deoxycortisol in their blood and excrete "pregnanetriolone" and "tetrahydro-S" in their urine. The simultaneous presence of these compounds suggests two enzymic deficiencies, which are expressed in C21- and C11 beta-hydroxylases, respectively. However, these deficiencies have been inferred to derive from a single aberration in C11 beta-hydroxylase, whereby the enzyme acquires an affinity towards 21-deoxy precursors (i.e. 17-OH-progesterone) of cortisol and diminishes its activity against its regular 21-hydroxy intermediate 11-deoxycortisol. Depending on the severity of the aberration varying amounts of 21-deoxycortisol (expressing the aberrant 11 beta-hydroxylase) and of 11-deoxycortisol (expressing the normal 11 beta-hydroxylase) will be formed. An apparent two-level inhibition of cortisol biosynthesis will result from: (1) the low activity of normal 21-hydroxylase on the derivative 21-deoxycortisol, produced by the action of the aberrant 11 beta-hydroxylase, and (2) the low supply of 11-deoxycortisol for the regular but decreased (due to the aberration) 11 beta-hydroxylase. Thus a single defect will mimic at one and the same time a 21-hydroxylase and a 11 beta-hydroxylase deficiency.
mesh_terms: D000293:Adolescent; D000302:Adrenal Cortex / Q000378:metabolism; D000312:Adrenal Hyperplasia, Congenital / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone; D000328:Adult; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010053:Ovary / Q000201:enzymology; D013250:Steroid Hydroxylases / Q000172:deficiency*
chemical_list: D005938:Glucocorticoids; D012739:Gonadal Steroid Hormones; D000324:Adrenocorticotropic Hormone; D013250:Steroid Hydroxylases; D006854:Hydrocortisone