To determine whether some patients with idiopathic hypospadias (146450) have a mutation in the HSD3B2 gene, Codner et al. (2004) conducted a prospective endocrine and molecular study in 90 patients with hypospadias and 101 healthy fertile male controls. They did not observe a clear steroidogenic pattern suggestive of 3-beta-HSD deficiency in any patient. Two patients had heterozygous missense mutations in the HSD3B2 gene; in another 3 patients, the authors observed heterozygous nucleotide variants in exon 4 that did not produce a change in amino acids. The authors concluded that subtle molecular abnormalities in the HSD3B2 gene may be observed in some patients with apparent idiopathic hypospadias but that this finding is uncommon.
The mineralocorticoid pathway starts with 21-hydroxylation of progesterone to form deoxycorticosterone (DOC). The enzyme in this reaction, 21-hydroxylase, is encoded by the CYP21 gene. 11 , 12 Deoxycorticosterone is then converted to corticosterone through the action of 11β-hydroxylase. There are two distinct 11β-hydroxylase isoenzymes, both of which are encoded by two genes, CYP11B1 and CYP11B2 . 13 Corticosterone is hydroxylated at carbon 18 to form 18-hydroxycorticosterone, which is transformed to aldosterone by removal of two hydrogens (oxidation) at carbon 18. These two reactions are catalyzed by 18-hydroxylase and 18-hydroxysteroid dehydrogenase, respectively, which are encoded by the same gene, CYP11B2 . Transcription of CYP11B1 is regulated primarily by ACTH, whereas angiotensin II regulates CYP11B2 transcription. 14 , 15 Similarly, the glucocorticoid pathway begins with 17α-hydroxyprogesterone, which is converted to deoxycortisol and subsequently to cortisol by 21-hydroxylase and 11β-hydroxylase, respectively, in the same manner as the conversion of progesterone to corticosterone. A deficiency of 21-hydroxylase, 11β-hydroxylase, or 3β-HSD in the adrenals may result in congenital adrenal hyperplasia and female pseudohermaphroditism, manifested as a masculinized female fetus.
HSD11B1 (Hydroxysteroid 11-Beta Dehydrogenase 1) is a Protein Coding gene. Diseases associated with HSD11B1 include Cortisone Reductase Deficiency 2 and Hyperandrogenism Due To Cortisone Reductase Deficiency . Among its related pathways are Metabolism and Steroid hormone biosynthesis . Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and 11-beta-hydroxysteroid dehydrogenase (NADP+) activity . An important paralog of this gene is HSD11B1L .