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Pathway Description
3-beta-Hydroxysteroid Dehydrogenase Deficiency
Homo sapiens
Disease Pathway
3-beta-hydroxysteroid dehydrogenase (HSD) deficiency is an extremely rare inborn error of metabolism (IEM) and autosomal recessive disorder of the steroidogenesis pathway. It is caused by an defect in the HSD3B2 gene which encodes for the 3 beta-hydroxysteroid dehydrogenase enzyme, which is responsible for forming cortisol from 11b,17a,21-trihydroxypregnenolone. When the enzyme is not correctly produced, cortisol levels in the cell are lowered, and as cortisol is used in the production of other steroids, it may affect their levels as well. 3-beta-HSD deficiency is characterized by low levels of cortisol produced in the adrenal glands. Symptoms include abnormal genitalia for both males and females, as well as infertility. There is also a more severe salt-wasting form of this deficiency, characterized by dehydration. Treatment for 3-beta-HSD deficiency includes steroid replacement, as well as sex hormone replacement during puberty to allow proper development. Surgery can also be used to correct any genital abnormalities that may occur. It is estimated that 3-beta-HSD deficiency affects less than 1 in 1,000,000 individuals, with around 60 cases reported.
References
3-beta-Hydroxysteroid Dehydrogenase Deficiency References
Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F: Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency. J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):127-38.
Pubmed: 7626445
Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S: Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency. J Clin Endocrinol Metab. 2002 Jun;87(6):2611-22. doi: 10.1210/jcem.87.6.8615.
Pubmed: 12050224
Pan Y, Zhong S, Hu RM, Gong W: Mutation of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) at the 3'-untranslated region is associated with adrenocortical insufficiency. Mol Med Rep. 2012 Dec;6(6):1305-8. doi: 10.3892/mmr.2012.1107. Epub 2012 Sep 28.
Pubmed: 23026940
Steroidogenesis References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Norman, A.W, and Litwack, G. Hormones (2nd ed.) (1997) San Diego : Academic Press.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Miller WL: Molecular biology of steroid hormone synthesis. Endocr Rev. 1988 Aug;9(3):295-318. doi: 10.1210/edrv-9-3-295.
Pubmed: 3061784
HECHTER O, SOLOMON MM, ZAFFARONI A, PINCUS G: Transformation of cholesterol and acetate to adrenal cortical hormones. Arch Biochem Biophys. 1953 Sep;46(1):201-14. doi: 10.1016/0003-9861(53)90182-9.
Pubmed: 13092959
Luu-The V: Assessment of steroidogenesis and steroidogenic enzyme functions. J Steroid Biochem Mol Biol. 2013 Sep;137:176-82. doi: 10.1016/j.jsbmb.2013.05.017. Epub 2013 Jun 13.
Pubmed: 23770321
George FW, Russell DW, Wilson JD: Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8044-7. doi: 10.1073/pnas.88.18.8044.
Pubmed: 1654556
Andersson S, Berman DM, Jenkins EP, Russell DW: Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature. 1991 Nov 14;354(6349):159-61. doi: 10.1038/354159a0.
Pubmed: 1944596
Emanuelsson I, Almokhtar M, Wikvall K, Gronbladh A, Nylander E, Svensson AL, Fex Svenningsen A, Norlin M: Expression and regulation of CYP17A1 and 3beta-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis. Neurochem Int. 2018 Feb;113:46-55. doi: 10.1016/j.neuint.2017.11.007. Epub 2017 Nov 21.
Pubmed: 29162485
Kimoto T, Asou H, Ohta Y, Mukai H, Chernogolov AA, Kawato S: Digital fluorescence imaging of elementary steps of neurosteroid synthesis in rat brain glial cells. J Pharm Biomed Anal. 1997 Jun;15(9-10):1231-40.
Pubmed: 9226548
Verschoor-Klootwyk AH, Verschoor L, Azhar S, Reaven GM: Role of exogenous cholesterol in regulation of adrenal steroidogenesis in the rat. J Biol Chem. 1982 Jul 10;257(13):7666-71.
Pubmed: 6282849
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