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Pathway Description
Androgen and Estrogen Metabolism
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-09-15
This pathway describes the inactivation and catabolism of male (androgen) and female (estrogen) hormones. Many steroid hormones are transformed by sulfatases, dehydrogenases and glucuronide transferases to enhance their solubility and to facilitate their elimination. Inactivation means to convert an active compound into an inactive compound. Peripheral inactivation, which is inactivation caused by outside enzymes such as liver enzymes for example, is needed to maintain a steady-state level of plasma. This means that if either of these hormones are to be “chemical signals”, their half-life in the bloodstream has to be limited so that a variation in secretion rate can be emulated in the plasma. A large part of inactivation/catabolism occurs in the liver, although a little bit of catabolic activity does happen in the kidneys. Inactive androgens and estrogens are mostly eliminated in the urine. For this to happen, androgen and estrogen need to be converted to compounds that are less hydrophobic so that they are more soluble at higher concentrations. In this pathway, the conversion to a hydrophilic compound is an oxidation of a 17b-hydroxyl group. These hormones are needed for sexual development in both males and females.
References
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 SMP0000068
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