Alternative titles; symbols
HGNC Approved Gene Symbol: HSD3B1
Cytogenetic location: 1p12 Genomic coordinates (GRCh38): 1:119,507,203-119,515,058 (from NCBI)
3-Beta-hydroxysteroid dehydrogenase catalyzes the oxidation and isomerization of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, thus leading to the formation of all classes of steroid hormones. The enzyme also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. HSD3B1 is expressed predominantly in placenta and skin, whereas HSD3B2 (613890) is expressed almost exclusively in adrenals and gonads (summary by Rheaume et al., 1991).
Luu-The et al. (1989) cloned an HSD3B1 cDNA from a human placenta cDNA library. The deduced HSD3B1 protein contains 372 amino acids. The HSD3B1 and HSD3B2 proteins share 93.5% sequence homology (Rheaume et al., 1991).
Doi et al. (2010) found that human HSD3B1 and HSD3B2 have 93.6% sequence identity, including the 5-prime and 3-prime untranslated regions. HSD3B subtype-specific quantitative RT-PCR analysis of mouse adrenal gland tissue revealed that expression of mouse Hsd3b6, which is the functional counterpart of HSD3B1, was considerably enriched in the aldosterone-producing zona glomerulosa cells of the adrenal gland, whereas expression of mouse Hsd3b2, which is the functional counterpart of HSD3B2, was predominantly expressed in zona fasciculata cells.
By in situ hybridization, Berube et al. (1989) demonstrated that a HSD3B gene is located in the chromosome 1p13 band. Also by in situ hybridization, Morrison et al. (1991) refined the localization to 1p13.1. Rheaume et al. (1991) demonstrated a BglII RFLP in the HSD3B1 gene and Rheaume et al. (1992) demonstrated linkage between this RFLP and mutations in the HSD3B2 gene. Thus, the 2 homologous genes, HSD3B1 and HSD3B2, are apparently both on chromosome 1p.
Bain et al. (1993) demonstrated that the genes encoding the gonadal and nongonadal forms of 3-beta-hydroxysteroid dehydrogenase are encoded by closely linked genes on mouse chromosome 3. They are located within a segment that is conserved on human chromosome 1. In fact, Bain et al. (1993) pointed out that 4 isoforms of the enzyme, and presumably 4 genes, have been identified in the mouse. The possibility of additional genes in the human was suggested.
Morissette et al. (1995) demonstrated that the HSD3B1 and HSD3B2 genes are located within a restriction fragment of approximately 290 kb.
Doi et al. (2010) studied Cry (see 601933)-null mice, which lack a functional circadian clock, and observed increased plasma aldosterone concentration and markedly suppressed plasma renin activity. Ex vivo tissue culture analysis showed that aldosterone production in the adrenal gland of Cry-null mice was found to be significantly higher than in wildtype mice. Microarray analysis showed markedly increased signal intensity of a gene probe that hybridizes with isoforms of the Hsd3b gene family; HSD3B subtype-specific quantitative RT-PCR analysis of mouse adrenal gland showed expression of only the Hsd3b1 and Hsd3b6 isoforms. Quantitative RT-PCR showed that the aberrantly expressed gene in Cry-null adrenal glands was Hsd3b6 rather than Hsd3b1 and that Hsd3b6 was constitutively increased across circadian time, in contrast to the lower expression of Hsd3b6 in wildtype mice which was subject to circadian fluctuation. In vitro promoter analysis revealed that transcription of Hsd3b6 is positively controlled by Dbp (124097). In situ hybridization studies confirmed the marked elevation of Hsd3b6 in Cry-null adrenal glands and showed that expression occurs almost exclusively in the aldosterone-producing cells of the zona glomerulosa. Blood pressure levels were similar in wildtype and Cry-null mice; however, the circadian variation in blood pressure characteristic for wildtype mice was completely lost in Cry-null mice, and Cry-null mice became hypertensive on a high-salt diet, whereas blood pressure in wildtype mice was unaffected. Doi et al. (2010) concluded that Hsd3b6 is a key enzyme through which Cry gene inactivation results in abnormally high plasma aldosterone concentration and salt-sensitive hypertension.
Bain, P. A., Meisler, M. H., Taylor, B. A., Payne, A. H. The genes encoding gonadal and nongonadal forms of 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase are closely linked on mouse chromosome 3. Genomics 16: 219-223, 1993. [PubMed: 8486361] [Full Text: https://doi.org/10.1006/geno.1993.1162]
Berube, D., Luu The, V., Lachance, Y., Gagne, R., Labrie, F. Assignment of the human 3 beta-hydroxysteroid dehydrogenase gene (HSDB3) to the p13 band of chromosome 1. Cytogenet. Cell Genet. 52: 199-200, 1989. [PubMed: 2630193] [Full Text: https://doi.org/10.1159/000132878]
Doi, M., Takahashi, Y., Komatsu, R., Yamazaki, F., Yamada, H., Haraguchi, S., Emoto, N., Okuno, Y., Tsujimoto, G., Kanematsu, A., Ogawa, O., Todo, T., Tsutsui, K., van der Horst, G. T. J., Okamura, H. Salt-sensitive hypertension in circadian clock-deficient Cry-null mice involves dysregulated adrenal Hsd3b6. Nature Med. 16: 67-74, 2010. [PubMed: 20023637] [Full Text: https://doi.org/10.1038/nm.2061]
Luu-The, V., Lachance, Y., Labrie, C., Leblanc, G., Thomas, J. L., Strickler, R. C., Labrie, F. Full-length cDNA structure and deduced amino acid sequence of human 3-beta-hydroxy-5-ene steroid dehydrogenase. Molec. Endocr. 3: 1310-1312, 1989. [PubMed: 2779585] [Full Text: https://doi.org/10.1210/mend-3-8-1310]
Morissette, J., Rheaume, E., Leblanc, J.-F., Luu-The, V., Labrie, F., Simard, J. Genetic linkage mapping of HSD3B1 and HSD3B2 encoding human types I and II 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4-isomerase close to D1S514 and the centromeric D1Z5 locus. Cytogenet. Cell Genet. 69: 59-62, 1995. [PubMed: 7835088] [Full Text: https://doi.org/10.1159/000133938]
Morrison, N., Nickson, D. A., McBride, M. W., Mueller, U. W., Boyd, E., Sutcliffe, R. G. Regional chromosomal assignment of human 3-beta-hydroxy-5-ene steroid dehydrogenase to 1p13.1 by non-isotopic in situ hybridisation. Hum. Genet. 87: 223-225, 1991. [PubMed: 2066113] [Full Text: https://doi.org/10.1007/BF00204189]
Rheaume, E., Lachance, Y., Zhao, H. F., Breton, N., Dumont, M., de Launoit, Y., Trudel, C., Luu-The, V., Simard, J., Labrie, F. Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads. Molec. Endocr. 5: 1147-1157, 1991. [PubMed: 1944309] [Full Text: https://doi.org/10.1210/mend-5-8-1147]
Rheaume, E., Leblanc, J. F., Lachance, Y., Labrie, F., Simard, J. Detection of frequent BglII polymorphism by polymerase chain reaction and TaqI restriction fragment length polymorphism for 3-beta-hydroxysteroid dehydrogenase/delta-5-delta-4 isomerase at the human HSDB3 locus (1p11-p13). Hum. Genet. 87: 753-754, 1991. [PubMed: 1682237] [Full Text: https://doi.org/10.1007/BF00201743]
Rheaume, E., Simard, J., Morel, Y., Mebarki, F., Zachmann, M., Forest, M. G., New, M. I., Labrie, F. Congenital adrenal hyperplasia due to point mutations in the type II 3-beta-hydroxysteroid dehydrogenase gene. Nature Genet. 1: 239-245, 1992. [PubMed: 1363812] [Full Text: https://doi.org/10.1038/ng0792-239]