11β-Hydroxytestosterone

December 2023vanc property raw P117 skin-invert-image 11β,17β-Dihydroxyandrost-4-en-3-one (1S,3aS,3bS,9aR,9bS,11aS)-1,10-Dihydroxy-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one 1816-85-9 correct CAS correct FDA BEF7K94MWQ 81481 486718 634-040-0 114920 C18075 102866 InChI=1S/C19H28O3/c1-18-8-7-12(20)9-11(18)3-4-13-14-5-6-16(22)19(14,2)10-15(21)17(13)18/h9,13-17,21-22H,3-8,10H2,1-2H3/t13-,14-,15-,16-,17+,18-,19-/m0/s1 C1C2=CC(CC[C@@]2([C@]3([C@H](C[C@]4([C@]([C@@]3(C1)[H])(CC[C@@H]4O)[H])C)O)[H])C)=O 19 28 3 08 Danger 351 360 201 202 281 308+313 405 501 11β-Hydroxytestosterone is an endogenous steroid, a metabolite of testosterone. Storbeck KH, Mostaghel EA Prostate Cancer Canonical and Noncanonical Androgen Metabolism and Activity Advances in Experimental Medicine and Biology 1210 239–277 2019 Springer 31900912 10.1007/978-3-030-32656-2_11 978-3-030-32655-5 209748543 CYP11B1 and 2 have also been shown to 11β-hydroxylate T, yielding 11β-hydroxytestosterone (11OHT), though the levels produced by the adrenal are low due to the limited availability of adrenal derived T Stárka L, Dušková M, Vítků J 11-Keto-testosterone and other androgens of adrenal origin Physiological Research 69 Suppl 2 S187–S192 September 2020 33094617 10.33549/physiolres.934516 8603739 free 29277707 2018 van Rooyen D, Gent R, Barnard L, Swart AC The in vitro metabolism of 11β-hydroxyprogesterone and 11-ketoprogesterone to 11-ketodihydrotestosterone in the backdoor pathway The Journal of Steroid Biochemistry and Molecular Biology 178 203–212 10.1016/j.jsbmb.2017.12.014 370013510.15347/WJM/2023.003 free Alternative androgen pathways 2023 Masiutin M, Yadav M WikiJournal of Medicine 10 X 257943362 Although it may not have significant androgenic activity, it may still be an important precursor to androgenic molecules. Chemical properties 11β-Hydroxytestosterone is an androstanoid with the molecular formula C19H28O3 and a molecular weight of 304.42 Da. Its IUPAC name is (8S,9S,10R,11S,13S,14S,17S)-11,17-dihydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one, reflecting its steroid structure with hydroxyl groups at the 11β and 17β positions and a 3-keto group on the A-ring. The compound is a 3-oxo-Δ4 steroid, structurally related to testosterone, with an additional hydroxyl group at the 11β-position, which reduces its androgenic potency but enables further metabolism into active androgens. It is moderately soluble in water due to its hydroxyl groups but more soluble in organic solvents like ethanol.11Beta-Hydroxytestosterone https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9753005.htm 2025-05-20 ChemicalBook Biosynthesis and metabolism 11β-Hydroxytestosterone is biosynthesized in the adrenal glands, primarily in the zona reticularis, through the action of cytochrome P450 11β-hydroxylase (CYP11B1), which catalyzes the hydroxylation of testosterone at the 11β-position. This enzyme, encoded by the CYP11B1 gene, is a mitochondrial P450 monooxygenase that also converts 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone, with weaker activity on testosterone. The reaction requires electron transfer from NADPH via adrenodoxin reductase and adrenodoxin, similar to other P450 systems. In adrenal tissue, testosterone, derived from androstenedione via 17β-hydroxysteroid dehydrogenase (17βHSD), is the precursor. Studies from the 1960s confirmed its production in human adrenal homogenates, with 11β-Hydroxytestosterone as the predominant metabolite of testosterone, alongside minor amounts of 11β-hydroxyandrostenedione (11OHA4) and 11-ketoandrostenedione (11KA4). Its biosynthesis is regulated by adrenocorticotropic hormone (ACTH), which upregulates CYP11B1 expression. In peripheral tissues, 11β-Hydroxytestosterone is metabolized by 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) to 11-ketotestosterone (11-KT), a more potent androgen, or by 5α-reductase to 11β-hydroxydihydrotestosterone (11OHDHT), both of which are androgen receptor (AR) agonists. Biological role 11β-Hydroxytestosterone has weak androgenic activity compared to testosterone or dihydrotestosterone (DHT) due to the 11β-hydroxyl group, which reduces its affinity for the androgen receptor. However, it is a critical precursor in the C11-oxy C19 steroid pathway, which produces potent androgens like 11-KT and 11-KDHT, particularly in peripheral tissues such as the prostate. This pathway challenges the traditional view that testosterone and DHT are the sole potent androgens in humans. Clinical relevance Polycystic Ovary Syndrome (PCOS): 11β-Hydroxytestosterone levels are elevated in PCOS patients, often exceeding testosterone levels, making it a potential biomarker for hyperandrogenism.Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11 beta-hydroxysteroid dehydrogenase N Engl J Med 1994 330 7 460–465 8289851 10.1056/NEJM199402173300703 Rodin A, Thakkar H, Taylor N, Clayton R Castration-Resistant Prostate Cancer (CRPC): The C11-oxy C19 pathway, including 11β-Hydroxytestosterone, contributes to androgen production in CRPC, where adrenal-derived 11OHA4 and 11OHT are metabolized to 11-KT and 11-KDHT in prostate tissue, sustaining tumor growth despite androgen deprivation therapy.11β-Hydroxydihydrotestosterone and 11-ketodihydrotestosterone, novel C19 steroids with androgenic activity Mol Cell Endocrinol 2013 377 1–2 135–146 23856005 10.1016/j.mce.2013.07.006 Storbeck KH, Bloem LM, Africander D, Schloms L, Swart P, Swart AC Congenital Adrenal Hyperplasia (CAH): Mutations in the CYP11B1 gene, which encodes 11β-hydroxylase, can lead to 11β-hydroxylase deficiency, increasing 11β-Hydroxytestosterone precursors like testosterone and androstenedione, contributing to virilization.Congenital adrenal hyperplasia N Engl J Med 2003 349 8 776–788 12930931 10.1056/NEJMra021561 Speiser PW, White PC Research Recent research has focused on the C11-oxy C19 steroid pathway, with 11β-Hydroxytestosterone identified as a key intermediate. A 2013 study in LNCaP prostate cancer cells demonstrated its conversion to 11-KT and 11-KDHT, highlighting its role in CRPC. A 2016 study confirmed its elevated levels in 21-hydroxylase deficiency, another form of CAH, where it contributes to adrenal androgen excess. Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency Eur J Endocrinol 2016 174 5 601–609 26865584 10.1530/EJE-15-1181 4874183 Turcu AF, Nanba AT, Chomic R, Upadhyay SK, Giordano TJ, Shields JJ, Merke DP, Rainey WE, Auchus RJ Detection in doping and testing Given its anabolic properties, 11β-Hydroxytestosterone is monitored in anti-doping testing. It can be detected in urine samples as part of testing for banned substances. Its detection helps identify the misuse of testosterone or other anabolic steroids, as athletes may attempt to mask their use of these substances by metabolizing testosterone into 11β-hydroxytestosterone. Specialized tests are used to measure the ratio of 11β-Hydroxytestosterone to testosterone, as a way to flag illicit use of exogenous substances.du Toit Therina Bloem Liezl M. Quanson Jonathan L. Ehlers Riaan Serafin Antonio M. Swart Amanda C. 2017 Profiling adrenal 11β-hydroxyandrostenedione metabolites in prostate cancer cells, tissue and plasma: UPC2-MS/MS quantification of 11β-hydroxytestosterone, 11keto-testosterone and 11keto-dihydrotestosterone The Journal of Steroid Biochemistry and Molecular Biology 166 54–67 10.1016/j.jsbmb.2016.06.009 1879-1220 27345701 See also Testosterone 4-Hydroxytestosterone References Category:Androstanes Category:Human metabolites