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Pathway Description
Steroidogenesis
Homo sapiens
Metabolic Pathway
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
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Norman, A.W, and Litwack, G. Hormones (2nd ed.) (1997) San Diego : Academic Press.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Miller WL: Molecular biology of steroid hormone synthesis. Endocr Rev. 1988 Aug;9(3):295-318. doi: 10.1210/edrv-9-3-295.
Pubmed: 3061784
HECHTER O, SOLOMON MM, ZAFFARONI A, PINCUS G: Transformation of cholesterol and acetate to adrenal cortical hormones. Arch Biochem Biophys. 1953 Sep;46(1):201-14. doi: 10.1016/0003-9861(53)90182-9.
Pubmed: 13092959
Luu-The V: Assessment of steroidogenesis and steroidogenic enzyme functions. J Steroid Biochem Mol Biol. 2013 Sep;137:176-82. doi: 10.1016/j.jsbmb.2013.05.017. Epub 2013 Jun 13.
Pubmed: 23770321
George FW, Russell DW, Wilson JD: Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8044-7. doi: 10.1073/pnas.88.18.8044.
Pubmed: 1654556
Andersson S, Berman DM, Jenkins EP, Russell DW: Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature. 1991 Nov 14;354(6349):159-61. doi: 10.1038/354159a0.
Pubmed: 1944596
Emanuelsson I, Almokhtar M, Wikvall K, Gronbladh A, Nylander E, Svensson AL, Fex Svenningsen A, Norlin M: Expression and regulation of CYP17A1 and 3beta-hydroxysteroid dehydrogenase in cells of the nervous system: Potential effects of vitamin D on brain steroidogenesis. Neurochem Int. 2018 Feb;113:46-55. doi: 10.1016/j.neuint.2017.11.007. Epub 2017 Nov 21.
Pubmed: 29162485
Kimoto T, Asou H, Ohta Y, Mukai H, Chernogolov AA, Kawato S: Digital fluorescence imaging of elementary steps of neurosteroid synthesis in rat brain glial cells. J Pharm Biomed Anal. 1997 Jun;15(9-10):1231-40.
Pubmed: 9226548
Verschoor-Klootwyk AH, Verschoor L, Azhar S, Reaven GM: Role of exogenous cholesterol in regulation of adrenal steroidogenesis in the rat. J Biol Chem. 1982 Jul 10;257(13):7666-71.
Pubmed: 6282849
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