Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
3-beta-Hydroxysteroid Dehydrogenase Deficiency
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2022-12-19
Last Updated: 2023-10-25
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. doi: 10.1016/0960-0760(95)00043-y.
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
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
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
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. doi: 10.1016/s0731-7085(96)01987-5.
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
Qin KN, New MI, Cheng KC: Molecular cloning of multiple cDNAs encoding human enzymes structurally related to 3 alpha-hydroxysteroid dehydrogenase. J Steroid Biochem Mol Biol. 1993 Dec;46(6):673-9.
Pubmed: 8274401
Khanna M, Qin KN, Wang RW, Cheng KC: Substrate specificity, gene structure, and tissue-specific distribution of multiple human 3 alpha-hydroxysteroid dehydrogenases. J Biol Chem. 1995 Aug 25;270(34):20162-8. doi: 10.1074/jbc.270.34.20162.
Pubmed: 7650035
Khanna M, Qin KN, Cheng KC: Distribution of 3 alpha-hydroxysteroid dehydrogenase in rat brain and molecular cloning of multiple cDNAs encoding structurally related proteins in humans. J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):41-6.
Pubmed: 7626489
Drury JE, Mindnich R, Penning TM: Characterization of disease-related 5beta-reductase (AKR1D1) mutations reveals their potential to cause bile acid deficiency. J Biol Chem. 2010 Aug 6;285(32):24529-37. doi: 10.1074/jbc.M110.127779. Epub 2010 Jun 3.
Pubmed: 20522910
Di Costanzo L, Drury JE, Penning TM, Christianson DW: Crystal structure of human liver Delta4-3-ketosteroid 5beta-reductase (AKR1D1) and implications for substrate binding and catalysis. J Biol Chem. 2008 Jun 13;283(24):16830-9. doi: 10.1074/jbc.M801778200. Epub 2008 Apr 11.
Pubmed: 18407998
Di Costanzo L, Drury JE, Christianson DW, Penning TM: Structure and catalytic mechanism of human steroid 5beta-reductase (AKR1D1). Mol Cell Endocrinol. 2009 Mar 25;301(1-2):191-8. doi: 10.1016/j.mce.2008.09.013. Epub 2008 Sep 19.
Pubmed: 18848863
Pascoe L, Curnow KM, Slutsker L, Rosler A, White PC: Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):4996-5000. doi: 10.1073/pnas.89.11.4996.
Pubmed: 1594605
Mitsuuchi Y, Kawamoto T, Naiki Y, Miyahara K, Toda K, Kuribayashi I, Orii T, Yasuda K, Miura K, Nakao K, et al.: Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients. Biochem Biophys Res Commun. 1992 Jan 31;182(2):974-9. doi: 10.1016/0006-291x(92)91827-d.
Pubmed: 1346492
Mitsuuchi Y, Kawamoto T, Miyahara K, Ulick S, Morton DH, Naiki Y, Kuribayashi I, Toda K, Hara T, Orii T, et al.: Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients. Biochem Biophys Res Commun. 1993 Feb 15;190(3):864-9. doi: 10.1006/bbrc.1993.1128.
Pubmed: 8439335
Naiki Y, Kawamoto T, Mitsuuchi Y, Miyahara K, Toda K, Orii T, Imura H, Shizuta Y: A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency. J Clin Endocrinol Metab. 1993 Dec;77(6):1677-82. doi: 10.1210/jcem.77.6.7903314.
Pubmed: 7903314
White PC, Dupont J, New MI, Leiberman E, Hochberg Z, Rosler A: A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin. J Clin Invest. 1991 May;87(5):1664-7. doi: 10.1172/JCI115182.
Pubmed: 2022736
Joehrer K, Geley S, Strasser-Wozak EM, Azziz R, Wollmann HA, Schmitt K, Kofler R, White PC: CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Hum Mol Genet. 1997 Oct;6(11):1829-34. doi: 10.1093/hmg/6.11.1829.
Pubmed: 9302260
Tannin GM, Agarwal AK, Monder C, New MI, White PC: The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. J Biol Chem. 1991 Sep 5;266(25):16653-8.
Pubmed: 1885595
Draper N, Echwald SM, Lavery GG, Walker EA, Fraser R, Davies E, Sorensen TI, Astrup A, Adamski J, Hewison M, Connell JM, Pedersen O, Stewart PM: Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism. J Clin Endocrinol Metab. 2002 Nov;87(11):4984-90. doi: 10.1210/jc.2001-011375.
Pubmed: 12414862
Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. doi: 10.1038/ng1285. Epub 2003 Dec 21.
Pubmed: 14702039
Higashi Y, Yoshioka H, Yamane M, Gotoh O, Fujii-Kuriyama Y: Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene. Proc Natl Acad Sci U S A. 1986 May;83(9):2841-5. doi: 10.1073/pnas.83.9.2841.
Pubmed: 3486422
White PC, New MI, Dupont B: Structure of human steroid 21-hydroxylase genes. Proc Natl Acad Sci U S A. 1986 Jul;83(14):5111-5. doi: 10.1073/pnas.83.14.5111.
Pubmed: 3487786
Rodrigues NR, Dunham I, Yu CY, Carroll MC, Porter RR, Campbell RD: Molecular characterization of the HLA-linked steroid 21-hydroxylase B gene from an individual with congenital adrenal hyperplasia. EMBO J. 1987 Jun;6(6):1653-61.
Pubmed: 3038528
Chung BC, Picado-Leonard J, Haniu M, Bienkowski M, Hall PF, Shively JE, Miller WL: Cytochrome P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues. Proc Natl Acad Sci U S A. 1987 Jan;84(2):407-11. doi: 10.1073/pnas.84.2.407.
Pubmed: 3025870
Picado-Leonard J, Miller WL: Cloning and sequence of the human gene for P450c17 (steroid 17 alpha-hydroxylase/17,20 lyase): similarity with the gene for P450c21. DNA. 1987 Oct;6(5):439-48. doi: 10.1089/dna.1987.6.439.
Pubmed: 3500022
Bradshaw KD, Waterman MR, Couch RT, Simpson ER, Zuber MX: Characterization of complementary deoxyribonucleic acid for human adrenocortical 17 alpha-hydroxylase: a probe for analysis of 17 alpha-hydroxylase deficiency. Mol Endocrinol. 1987 May;1(5):348-54. doi: 10.1210/mend-1-5-348.
Pubmed: 3274893
Highlighted elements will appear in red.
Highlight Compounds
Highlight Proteins
Enter relative concentration values (without units). Elements will be highlighted in a color gradient where red = lowest concentration and green = highest concentration. For the best results, view the pathway in Black and White.
Visualize Compound Data
Visualize Protein Data
Downloads
Settings