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Pathway Description
17-beta Hydroxysteroid Dehydrogenase III Deficiency
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Disease
Created: 2018-09-10
Last Updated: 2019-09-15
17-beta hydroxysteroid dehydrogenase III deficiency, also known as 17-KSR deficiency or male pseudohermaphroditism with gynecomastia (MPH), is as rare inborn error of metabolism (IEM) and autosomal recessive disorder of the androgen and estrogen metabolism pathway. It is caused by a mutation in the HSD17B3 gene, which encodes the enzyme testosterone 17-beta-dehydrogenase 3, which is responsible for catalyzing the reversible formation of androstenedione from testosterone. This leads to an accumulation of androstenedione and dehydroepiandrosterone in the body, as well as a lack of testosterone produced. 17-KSR deficiency is characterized by an absence of testosterone in the testis until puberty, where testosterone is produced outside of the gonads. Symptoms include infertility and external female genitalia until puberty, when secondary male sex characteristics occur, as well as gynecomastia. Due to this, many individuals with this disorder are raised as female despite being genetically male, until puberty. Treatment can include removal of testes before puberty, preventing any masculinization at puberty, as well as surgical treatment of genitalia. However, there is no known treatment for restoring the fertility of affected individuals. It is estimated that 17-KSR deficiency affects 1 in 150,000 individuals in The Netherlands, without much information for the rest of the world.
References
17-beta Hydroxysteroid Dehydrogenase III Deficiency References
Andersson S, Geissler WM, Wu L, Davis DL, Grumbach MM, New MI, Schwarz HP, Blethen SL, Mendonca BB, Bloise W, Witchel SF, Cutler GB Jr, Griffin JE, Wilson JD, Russel DW: Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency. J Clin Endocrinol Metab. 1996 Jan;81(1):130-6. doi: 10.1210/jcem.81.1.8550739.
Pubmed: 8550739
Androgen and Estrogen Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Norman, A.W, and Litwack, G. Hormones (2nd ed.) (1997) San Diego : Academic Press.
Song WC, Moore R, McLachlan JA, Negishi M: Molecular characterization of a testis-specific estrogen sulfotransferase and aberrant liver expression in obese and diabetogenic C57BL/KsJ-db/db mice. Endocrinology. 1995 Jun;136(6):2477-84. doi: 10.1210/endo.136.6.7750469.
Pubmed: 7750469
Kakuta Y, Pedersen LG, Carter CW, Negishi M, Pedersen LC: Crystal structure of estrogen sulphotransferase. Nat Struct Biol. 1997 Nov;4(11):904-8.
Pubmed: 9360604
Kakuta Y, Petrotchenko EV, Pedersen LC, Negishi M: The sulfuryl transfer mechanism. Crystal structure of a vanadate complex of estrogen sulfotransferase and mutational analysis. J Biol Chem. 1998 Oct 16;273(42):27325-30. doi: 10.1074/jbc.273.42.27325.
Pubmed: 9765259
Terashima M, Toda K, Kawamoto T, Kuribayashi I, Ogawa Y, Maeda T, Shizuta Y: Isolation of a full-length cDNA encoding mouse aromatase P450. Arch Biochem Biophys. 1991 Mar;285(2):231-7. doi: 10.1016/0003-9861(91)90354-l.
Pubmed: 1897929
Nokelainen P, Puranen T, Peltoketo H, Orava M, Vihko P, Vihko R: Molecular cloning of mouse 17 beta-hydroxysteroid dehydrogenase type 1 and characterization of enzyme activity. Eur J Biochem. 1996 Mar 1;236(2):482-90. doi: 10.1111/j.1432-1033.1996.00482.x.
Pubmed: 8612620
Kimura T, Owens IS: Mouse UDP glucuronosyltransferase. cDNA and complete amino acid sequence and regulation. Eur J Biochem. 1987 Nov 2;168(3):515-21. doi: 10.1111/j.1432-1033.1987.tb13448.x.
Pubmed: 3117546
Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001.
Pubmed: 21183079
Youngblood GL, Sartorius C, Taylor BA, Payne AH: Isolation, characterization, and chromosomal mapping of mouse P450 17 alpha-hydroxylase/C17-20 lyase. Genomics. 1991 May;10(1):270-5.
Pubmed: 1840559
Carninci P, Hayashizaki Y: High-efficiency full-length cDNA cloning. Methods Enzymol. 1999;303:19-44. doi: 10.1016/s0076-6879(99)03004-9.
Pubmed: 10349636
Carninci P, Shibata Y, Hayatsu N, Sugahara Y, Shibata K, Itoh M, Konno H, Okazaki Y, Muramatsu M, Hayashizaki Y: Normalization and subtraction of cap-trapper-selected cDNAs to prepare full-length cDNA libraries for rapid discovery of new genes. Genome Res. 2000 Oct;10(10):1617-30. doi: 10.1101/gr.145100.
Pubmed: 11042159
Shibata K, Itoh M, Aizawa K, Nagaoka S, Sasaki N, Carninci P, Konno H, Akiyama J, Nishi K, Kitsunai T, Tashiro H, Itoh M, Sumi N, Ishii Y, Nakamura S, Hazama M, Nishine T, Harada A, Yamamoto R, Matsumoto H, Sakaguchi S, Ikegami T, Kashiwagi K, Fujiwake S, Inoue K, Togawa Y: RIKEN integrated sequence analysis (RISA) system--384-format sequencing pipeline with 384 multicapillary sequencer. Genome Res. 2000 Nov;10(11):1757-71. doi: 10.1101/gr.152600.
Pubmed: 11076861
Sakakibara Y, Yanagisawa K, Takami Y, Nakayama T, Suiko M, Liu MC: Molecular cloning, expression, and functional characterization of novel mouse sulfotransferases. Biochem Biophys Res Commun. 1998 Jun 29;247(3):681-6. doi: 10.1006/bbrc.1998.8872.
Pubmed: 9647753
Shimizu C, Fuda H, Yanai H, Strott CA: Conservation of the hydroxysteroid sulfotransferase SULT2B1 gene structure in the mouse: pre- and postnatal expression, kinetic analysis of isoforms, and comparison with prototypical SULT2A1. Endocrinology. 2003 Apr;144(4):1186-93. doi: 10.1210/en.2002-221011.
Pubmed: 12639899
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000356
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