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Pathway Description
17-alpha-Hydroxylase Deficiency (CYP17)
Homo sapiens
Disease Pathway
17-alpha-hydroxylase deficiency, also known as congenital adrenal hyperplasia (CAH) due to 17-alpha-hydroxylase deficiency or congenital adrenal hyperplasia type 5, is a rare inborn error of metabolism (IEM) and autosomal recessive disorder of the steroidogenesis pathway. It is caused by a mutation in the CYP17A1 gene which encodes the enzyme steroid 17-alpha-hydroxylase. This enzyme hydroxylates both progesterone and pregnenolone into 17-hydroxyprogesterone and 17a-hydroxypregnenolone respectively in the mitochondria, as well as hydroxylating 21-deoxycortisol to 11b-hydroxyprogesterone within the endoplasmic reticulum. When mutated, it leads to an accumulation of pregnenolone, progesterone, deoxycorticosterone and 11-dehydrocorticosterone throughout the cell. 17-alpha hydroxylase deficiency is characterized by a deficiency of sex steroids, as well as glucocorticoids. Symptoms include male undervirilization, as well as lack of development during puberty including amenorrhea for females. Low levels of potassium in the blood due to the increased levels of mineralocorticoids can occur, as well as hypertension. Treatment with dexamethasone has been able to normalize blood pressure and blood potassium levels. It is estimated that 17-alpha-hydroxylase deficiency affects 1 in 1,000,000 individuals.
References
17-alpha-Hydroxylase Deficiency (CYP17) References
[Metagen: 17-ALPHA-HYDROXYLASE DEFICIENCY (CYP17)](http://metagene.de/program/d.prg?id_d=321)
[OMIM: 202110](http://omim.org/entry/202110})
[NIH](http://en.wikipedia.org/wiki/Adrenal_hyperplasia,_congenital)
Biglieri EG: 17 Alpha-hydroxylase deficiency. J Endocrinol Invest. 1995 Jul-Aug;18(7):540-4.
Pubmed: 9221272
Auchus RJ: Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. J Steroid Biochem Mol Biol. 2017 Jan;165(Pt A):71-78. doi: 10.1016/j.jsbmb.2016.02.002. Epub 2016 Feb 6.
Pubmed: 26862015
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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