21-hydroxylase, a major autoantigen in idiopathic Addison's disease

Premature Ovarian Failure and Ovarian Autoimmunity

“…However, in the one such patient with St-C-Abs, 17-␣-OH was not recognized (191). To the authors' knowledge, studies have not been published on correlations between the presence and activity of St-C-Abs and autoantibodies to either 17-␣-OH or p450-scc in patients without APGS type 1.…”

“…It has been found that the adrenal cytochrome p450 enzyme 21 hydroxylase (which converts 17-␣-progesterone and progesterone into 11-deoxy- (191,192), either in the form of isolated adrenal failure or associated with hypothyroidism (type II APGS). In type I APGS it is thought that autoantibodies are directed to other members of the cytochrome p450 enzyme family, namely to the p450 side-chain cleavage enzyme (p450-scc) and to 17-␣-hydroxylase (17-␣-OH) (192)(193)(194)(195)(196), and to an ill-defined 51-kDa protein (197).…”

Adrenal and ovarian autoimmunity

“…In the same year screening of a human fetal adrenal cDNA library with the sera from patients with AAD in the context of PGAD type 1 allowed isolation of clones with high homology to steroid 17a-hydroxylase (17a-OH) and this study indicated that 17a-OH was an autoantigen associated with the AAD in the context of PGAD type 1 (53). Reactivity of sera from patients with PGAD type 1 with cytochrome P450 side chain cleavage enzyme (P450scc) was reported soon afterwards (52). Reports on identification of 21-OH as a major adrenal autoantigen were confirmed by studies in several laboratories using different methods, including Western blotting or immunoprecipitation analyses based on native or recombinant 21-OH expressed in bacteria, yeast, mammalian cells or in vitro transcription/translation system (54-57).…”

“…This was followed, in 1992, by the identification, independently in two laboratories, of steroid 21-hydroxylase (21-OH) as a major adrenal autoantigen (50)(51)(52). In the same year screening of a human fetal adrenal cDNA library with the sera from patients with AAD in the context of PGAD type 1 allowed isolation of clones with high homology to steroid 17a-hydroxylase (17a-OH) and this study indicated that 17a-OH was an autoantigen associated with the AAD in the context of PGAD type 1 (53).…”

Ovarian autoimmune disease: clinical concepts and animal models

“…21 More than 80% of patients with autoimmune Addison's disease possess serum antibodies that recognize the adrenal cortex (adrenal cortex antibodies, ACAs). 22 All women identified to date with histological evidence of autoimmune oophoritis possess ACA; paradoxically, the major target of ACA, 21-hydroxylase (CYP21A2), [22][23][24] is not expressed in the ovary. In addition to autoantibodies to CYP21A2, autoantibodies to two other steroidogenic enzymes, P450 side chain cleavage (CYP11A1) and 17a-hydroxylase (CYP17), which convert cholesterol to pregnenolone, and progesterone to 17-hydroxyprogesterone, respectively, are present.…”