Chemistry:11β-Hydroxytestosterone
| Names | |
|---|---|
| IUPAC name
11β,17β-Dihydroxyandrost-4-en-3-one
| |
| Systematic IUPAC name
(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 | |
| Identifiers | |
3D model (JSmol)
|
|
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| EC Number |
|
| KEGG | |
PubChem CID
|
|
| UNII | |
| |
| |
| Properties | |
| C19H28O3 | |
| Molar mass | 304.430 g·mol−1 |
| Hazards | |
| GHS pictograms | 
|
| GHS Signal word | Danger |
| H351, H360 | |
| P201, P202, P281, P308+313, P405, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
| Infobox references | |
11β-Hydroxytestosterone is an endogenous steroid, a metabolite of testosterone.[1][2][3][4] Although it may not have significant androgenic activity, it may still be an important precursor to androgenic molecules.[4]
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.[5]
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), serves as 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.[6]
- 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.[7]
- 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.[8]
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. [9]
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.[10]
See also
References
- ↑ "Canonical and Noncanonical Androgen Metabolism and Activity". Prostate Cancer. Advances in Experimental Medicine and Biology. 1210. Springer. 2019. pp. 239–277. doi:10.1007/978-3-030-32656-2_11. ISBN 978-3-030-32655-5. "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"
- ↑ "11-Keto-testosterone and other androgens of adrenal origin". Physiological Research 69 (Suppl 2): S187–S192. September 2020. doi:10.33549/physiolres.934516. PMID 33094617.
- ↑ "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. 2018. doi:10.1016/j.jsbmb.2017.12.014. PMID 29277707.
- ↑ 4.0 4.1 "Alternative androgen pathways". WikiJournal of Medicine 10: X. 2023. doi:10.15347/WJM/2023.003.
- ↑ "11Beta-Hydroxytestosterone". ChemicalBook. https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9753005.htm.
- ↑ "Hyperandrogenism in polycystic ovary syndrome. Evidence of dysregulation of 11 beta-hydroxysteroid dehydrogenase". N Engl J Med 330 (7): 460–465. 1994. doi:10.1056/NEJM199402173300703. PMID 8289851.
- ↑ "11β-Hydroxydihydrotestosterone and 11-ketodihydrotestosterone, novel C19 steroids with androgenic activity". Mol Cell Endocrinol 377 (1–2): 135–146. 2013. doi:10.1016/j.mce.2013.07.006. PMID 23856005.
- ↑ "Congenital adrenal hyperplasia". N Engl J Med 349 (8): 776–788. 2003. doi:10.1056/NEJMra021561. PMID 12930931.
- ↑ "Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency". Eur J Endocrinol 174 (5): 601–609. 2016. doi:10.1530/EJE-15-1181. PMID 26865584.
- ↑ 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. doi:10.1016/j.jsbmb.2016.06.009. ISSN 1879-1220. PMID 27345701.
 |  |
