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Pathway Description
Steroidogenesis
Rattus norvegicus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
Last Updated: 2019-08-16
Steroidogenesis is a process that through the transformations of other steroids, produces a desired steroid. Some of these desired steroids include cortisol, corticoids, testosterone, estrogens, aldosterone and progesterone. To begin the synthesis of steroid hormones, cholesterol synthesizes a hormone called pregnenolone. This is done by cholesterol from the cytosol or lysosome being brought to the mitochondria and becoming fixed in the inner mitochondrial membrane. Once there, the cholesterol becomes pregnenolone through three reactions. The enzyme responsible for catalyzing all three reactions is CYP11A, a side chain cleavage enzyme. After being created, the pregnenolone enters the cytosol, where the cholesterol originated. Once in the cytosol, pregenolone synthesizes progesterone, using two reactions. These two reactions are both catalyzed by an enzyme called 3-beta-hydroxysteroid dehydrogenase/isomerase. The enzyme CYP21A2 then hydroxylates progesterone, which converts it to deoxycorticosterone. Deoxycorticosterone then undergoes three reactions catalyzed by CYP11B2 to become aldosterone. 17alpha-hydroxyprogesterone is created from pregnenolone by using 3-beta-hydroxysteroid dehydrogenase/isomerase. CYP21A2 then hydroxylates 17alpha-hydroxyprogesterone which results in the production of 11-deoxycortisol. CYP11B1 quickly converts 11-deoxycortisol to cortisol. Cortisol is an active steroid hormone, and its conversion to the inactive cortisone has been known to occur in various tissues, with increased conversion occurring in the liver. Pregnenolone is an important hormone as it is responsible for the beginning of the synthesis of many hormones not pictured in this pathway such as testosterone and estrogen. Cortisol receptors are found in almost every bodily cell, so this hormone affects a wide range of body functions. Some of these functions include metabolism regulation, inflammation reduction, regulating blood sugar levels and blood pressure, and helps with the formation of memories.
References
Steroidogenesis References
Pawlowski JE, Huizinga M, Penning TM: Cloning and sequencing of the cDNA for rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase. J Biol Chem. 1991 May 15;266(14):8820-5.
Pubmed: 1840601
Stolz A, Rahimi-Kiani M, Ameis D, Chan E, Ronk M, Shively JE: Molecular structure of rat hepatic 3 alpha-hydroxysteroid dehydrogenase. A member of the oxidoreductase gene family. J Biol Chem. 1991 Aug 15;266(23):15253-7.
Pubmed: 1714456
Cheng KC, White PC, Qin KN: Molecular cloning and expression of rat liver 3 alpha-hydroxysteroid dehydrogenase. Mol Endocrinol. 1991 Jun;5(6):823-8. doi: 10.1210/mend-5-6-823.
Pubmed: 1922097
Onishi Y, Noshiro M, Shimosato T, Okuda K: Molecular cloning and sequence analysis of cDNA encoding delta 4-3-ketosteroid 5 beta-reductase of rat liver. FEBS Lett. 1991 Jun 3;283(2):215-8. doi: 10.1016/0014-5793(91)80591-p.
Pubmed: 1710579
Onishi Y, Noshiro M, Shimosato T, Okuda K: delta 4-3-Oxosteroid 5 beta-reductase. Structure and function. Biol Chem Hoppe Seyler. 1991 Dec;372(12):1039-49.
Pubmed: 1789929
Zhu Y, Fillenwarth MJ, Crabb D, Lumeng L, Lin RC: Identification of the 37-kd rat liver protein that forms an acetaldehyde adduct in vivo as delta 4-3-ketosteroid 5 beta-reductase. Hepatology. 1996 Jan;23(1):115-22. doi: 10.1002/hep.510230116.
Pubmed: 8550030
Matsukawa N, Nonaka Y, Ying Z, Higaki J, Ogihara T, Okamoto M: Molecular cloning and expression of cDNAS encoding rat aldosterone synthase: variants of cytochrome P-450(11 beta). Biochem Biophys Res Commun. 1990 May 31;169(1):245-52. doi: 10.1016/0006-291x(90)91460-a.
Pubmed: 2350348
Okamoto M, Nonaka Y: Molecular biology of rat steroid 11 beta-hydroxylase [P450(11 beta)] and aldosterone synthase [P450(11 beta, aldo)]. J Steroid Biochem Mol Biol. 1992 Mar;41(3-8):415-9. doi: 10.1016/0960-0760(92)90367-r.
Pubmed: 1562515
Imai M, Shimada H, Okada Y, Matsushima-Hibiya Y, Ogishima T, Ishimura Y: Molecular cloning of a cDNA encoding aldosterone synthase cytochrome P-450 in rat adrenal cortex. FEBS Lett. 1990 Apr 24;263(2):299-302. doi: 10.1016/0014-5793(90)81398-8.
Pubmed: 2129527
Agarwal AK, Monder C, Eckstein B, White PC: Cloning and expression of rat cDNA encoding corticosteroid 11 beta-dehydrogenase. J Biol Chem. 1989 Nov 15;264(32):18939-43.
Pubmed: 2808402
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
Moisan MP, Edwards CR, Seckl JR: Differential promoter usage by the rat 11 beta-hydroxysteroid dehydrogenase gene. Mol Endocrinol. 1992 Jul;6(7):1082-7. doi: 10.1210/mend.6.7.1508221.
Pubmed: 1508221
Zhou MY, del Carmen Vila M, Gomez-Sanchez EP, Gomez-Sanchez CE: Cloning of two alternatively spliced 21-hydroxylase CDNAs from rat adrenal. J Steroid Biochem Mol Biol. 1997 Jul;62(4):277-86.
Pubmed: 9408081
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
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 SMP0000130
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