Loading Pathway...
Error: Pathway image not found.
Hide
Pathway Description
Metabolism and Physiological Effects of Androsterone sulfate
Homo sapiens
Metabolic Pathway
Created: 2023-09-07
Last Updated: 2023-11-27
Androsterone sulfate (Andros-S) is the most abundant 5-alpha-reduced androgen metabolite in serum. Androsterone sulfate is clinically recognized as one of the major androgen metabolites found in urine. It is a cognate substrate for human dehydroepiandrosterone sulfotransferase, which catalyzes the transfer of the sulfonate group from 3'-phosphoadenosine-5'-phosphosulfate to dehydroepiandrosterone (DHEA). Androsterone sulfate has been identified in the human placenta. Testosterone is the primary male sex hormone and anabolic steroid in males. Like other steroid hormones, testosterone is derived from cholesterol. The largest amounts of testosterone (>95%) are produced by the testes in men, while the adrenal glands account for most of the remainder. Both testosterone and 5α-DHT are metabolized mainly in the liver. Approximately 50% of testosterone is metabolized via conjugation into testosterone glucuronide and to a lesser extent testosterone sulfate by glucuronosyltransferases and sulfotransferases, respectively. In the hepatic 17-ketosteroid pathway of testosterone metabolism, testosterone is converted in the liver by 5α-reductase and 5β-reductase into 5α-DHT and the inactive 5β-DHT, respectively. Then, 5α-DHT and 5β-DHT are converted by 3α-HSD into 3α-androstanediol and 3α-etiocholanediol, respectively. Subsequently, 3α-androstanediol and 3α-etiocholanediol are converted by 17β-HSD into androsterone and etiocholanolone, which is followed by their conjugation and excretion. Androsterone has generally been considered to be an inactive metabolite of testosterone, which when conjugated by glucuronidation and sulfation allows testosterone to be removed from the body. Androsterone is sulfated into androsterone sulfate. Androsterone sulfate, also known as 3α-hydroxy-5α-androstan-17-one 3α-sulfate, is an endogenous, naturally occurring steroid and one of the major urinary metabolites of androgens. It is a steroid sulfate which is formed from sulfation of androsterone by the steroid sulfotransferase SULT2A1 and can be desulfated back into androsterone by steroid sulfatase.
References
Metabolism and Physiological Effects of Androsterone sulfate References
Bansal P, Morgat A, Axelsen KB, Muthukrishnan V, Coudert E, Aimo L, Hyka-Nouspikel N, Gasteiger E, Kerhornou A, Neto TB, Pozzato M, Blatter MC, Ignatchenko A, Redaschi N, Bridge A: Rhea, the reaction knowledgebase in 2022. Nucleic Acids Res. 2022 Jan 7;50(D1):D693-D700. doi: 10.1093/nar/gkab1016.
Pubmed: 34755880
Tanaka H, Sirich TL, Plummer NS, Weaver DS, Meyer TW: An Enlarged Profile of Uremic Solutes. PLoS One. 2015 Aug 28;10(8):e0135657. doi: 10.1371/journal.pone.0135657. eCollection 2015.
Pubmed: 26317986
Wishart DS, Guo A, Oler E, Wang F, Anjum A, Peters H, Dizon R, Sayeeda Z, Tian S, Lee BL, Berjanskii M, Mah R, Yamamoto M, Jovel J, Torres-Calzada C, Hiebert-Giesbrecht M, Lui VW, Varshavi D, Varshavi D, Allen D, Arndt D, Khetarpal N, Sivakumaran A, Harford K, Sanford S, Yee K, Cao X, Budinski Z, Liigand J, Zhang L, Zheng J, Mandal R, Karu N, Dambrova M, Schioth HB, Greiner R, Gautam V: HMDB 5.0: the Human Metabolome Database for 2022. Nucleic Acids Res. 2022 Jan 7;50(D1):D622-D631. doi: 10.1093/nar/gkab1062.
Pubmed: 34986597
Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA: The Regulation of Steroid Action by Sulfation and Desulfation. Endocr Rev. 2015 Oct;36(5):526-63. doi: 10.1210/er.2015-1036. Epub 2015 Jul 27.
Pubmed: 26213785
Zwicker H, Rittmaster RS: Androsterone sulfate: physiology and clinical significance in hirsute women. J Clin Endocrinol Metab. 1993 Jan;76(1):112-6. doi: 10.1210/jcem.76.1.8380602.
Pubmed: 8380602
Chang HJ, Shi R, Rehse P, Lin SX: Identifying androsterone (ADT) as a cognate substrate for human dehydroepiandrosterone sulfotransferase (DHEA-ST) important for steroid homeostasis: structure of the enzyme-ADT complex. J Biol Chem. 2004 Jan 23;279(4):2689-96. doi: 10.1074/jbc.M310446200. Epub 2003 Oct 21.
Pubmed: 14573603
Kamrath C, Hochberg Z, Hartmann MF, Remer T, Wudy SA: Increased activation of the alternative "backdoor" pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis. J Clin Endocrinol Metab. 2012 Mar;97(3):E367-75. doi: 10.1210/jc.2011-1997. Epub 2011 Dec 14.
Pubmed: 22170725
Janeczko A, Skoczowski A: Mammalian sex hormones in plants. Folia Histochem Cytobiol. 2005;43(2):71-9.
Pubmed: 16044944
Penning TM: New frontiers in androgen biosynthesis and metabolism. Curr Opin Endocrinol Diabetes Obes. 2010 Jun;17(3):233-9. doi: 10.1097/MED.0b013e3283381a31.
Pubmed: 20186052
Andersson S, Russell DW: Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases. Proc Natl Acad Sci U S A. 1990 May;87(10):3640-4. doi: 10.1073/pnas.87.10.3640.
Pubmed: 2339109
Jenkins EP, Hsieh CL, Milatovich A, Normington K, Berman DM, Francke U, Russell DW: Characterization and chromosomal mapping of a human steroid 5 alpha-reductase gene and pseudogene and mapping of the mouse homologue. Genomics. 1991 Dec;11(4):1102-12.
Pubmed: 1686016
Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL: Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9543-8. doi: 10.1073/pnas.160270997.
Pubmed: 10931946
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
Biswas MG, Russell DW: Expression cloning and characterization of oxidative 17beta- and 3alpha-hydroxysteroid dehydrogenases from rat and human prostate. J Biol Chem. 1997 Jun 20;272(25):15959-66. doi: 10.1074/jbc.272.25.15959.
Pubmed: 9188497
Huang XF, Luu-The V: Molecular characterization of a first human 3(alpha-->beta)-hydroxysteroid epimerase. J Biol Chem. 2000 Sep 22;275(38):29452-7. doi: 10.1074/jbc.M000562200.
Pubmed: 10896656
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
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