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Pathway Description
17-beta Hydroxysteroid Dehydrogenase III Deficiency
Rattus norvegicus
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
Rikke BA, Roy AK: Structural relationships among members of the mammalian sulfotransferase gene family. Biochim Biophys Acta. 1996 Jul 17;1307(3):331-8. doi: 10.1016/0167-4781(96)00065-6.
Pubmed: 8688469
Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871.
Pubmed: 22673903
Hickey GJ, Krasnow JS, Beattie WG, Richards JS: Aromatase cytochrome P450 in rat ovarian granulosa cells before and after luteinization: adenosine 3',5'-monophosphate-dependent and independent regulation. Cloning and sequencing of rat aromatase cDNA and 5' genomic DNA. Mol Endocrinol. 1990 Jan;4(1):3-12. doi: 10.1210/mend-4-1-3.
Pubmed: 2157976
Lephart ED, Peterson KG, Noble JF, George FW, McPhaul MJ: The structure of cDNA clones encoding the aromatase P-450 isolated from a rat Leydig cell tumor line demonstrates differential processing of aromatase mRNA in rat ovary and a neoplastic cell line. Mol Cell Endocrinol. 1990 Mar 26;70(1):31-40. doi: 10.1016/0303-7207(90)90056-e.
Pubmed: 2340950
Ghersevich S, Nokelainen P, Poutanen M, Orava M, Autio-Harmainen H, Rajaniemi H, Vihko R: Rat 17 beta-hydroxysteroid dehydrogenase type 1: primary structure and regulation of enzyme expression in rat ovary by diethylstilbestrol and gonadotropins in vivo. Endocrinology. 1994 Oct;135(4):1477-87. doi: 10.1210/endo.135.4.7925110.
Pubmed: 7925110
Akinola LA, Poutanen M, Vihko R: Cloning of rat 17 beta-hydroxysteroid dehydrogenase type 2 and characterization of tissue distribution and catalytic activity of rat type 1 and type 2 enzymes. Endocrinology. 1996 May;137(5):1572-9. doi: 10.1210/endo.137.5.8612487.
Pubmed: 8612487
Akinola LA, Poutanen M, Peltoketo H, Vihko R, Vihko P: Characterization of rat 17 beta-hydroxysteroid dehydrogenase type 1 gene and mRNA transcripts. Gene. 1998 Feb 27;208(2):229-38. doi: 10.1016/s0378-1119(97)00669-0.
Pubmed: 9524272
Fevold HR, Lorence MC, McCarthy JL, Trant JM, Kagimoto M, Waterman MR, Mason JI: Rat P450(17 alpha) from testis: characterization of a full-length cDNA encoding a unique steroid hydroxylase capable of catalyzing both delta 4- and delta 5-steroid-17,20-lyase reactions. Mol Endocrinol. 1989 Jun;3(6):968-75. doi: 10.1210/mend-3-6-968.
Pubmed: 2786990
Namiki M, Kitamura M, Buczko E, Dufau ML: Rat testis P-450(17)alpha cDNA: the deduced amino acid sequence, expression and secondary structural configuration. Biochem Biophys Res Commun. 1988 Dec 15;157(2):705-12. doi: 10.1016/s0006-291x(88)80307-3.
Pubmed: 3264499
Givens CR, Zhang P, Bair SR, Mellon SH: Transcriptional regulation of rat cytochrome P450c17 expression in mouse Leydig MA-10 and adrenal Y-1 cells: identification of a single protein that mediates both basal and cAMP-induced activities. DNA Cell Biol. 1994 Nov;13(11):1087-98. doi: 10.1089/dna.1994.13.1087.
Pubmed: 7702752
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Pubmed: 15057822
Florea L, Di Francesco V, Miller J, Turner R, Yao A, Harris M, Walenz B, Mobarry C, Merkulov GV, Charlab R, Dew I, Deng Z, Istrail S, Li P, Sutton G: Gene and alternative splicing annotation with AIR. Genome Res. 2005 Jan;15(1):54-66. doi: 10.1101/gr.2889405.
Pubmed: 15632090
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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