Chemistry:11β-Hydroxyprogesterone
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| IUPAC name
11β-Hydroxypregn-4-ene-3,20-dione
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| Systematic IUPAC name
(1S,3aS,3bS,9aR,9bS,10S,11aS)-1-Acetyl-10-hydroxy-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one | |
| Other names
11β-OHP; 21-Deoxycorticosterone; 21-Desoxycorticosterone
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| Identifiers | |
3D model (JSmol)
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PubChem CID
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| Properties | |
| C21H30O3 | |
| Molar mass | 330.468 g/mol |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
| Infobox references | |
11β-Hydroxyprogesterone (11β-OHP), also known as 21-deoxycorticosterone, as well as 11β-hydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid and derivative of progesterone.[1] It is a potent mineralocorticoid.[1] Syntheses of 11β-OHP from progesterone is catalyzed by the steroid 11β-hydroxylase (CYP11B1) enzyme,[2][3] and, to a lesser extent, by the aldosterone synthase enzyme (CYP11B2).[2]
Function
Along with its epimer 11α-hydroxyprogesterone (11α-OHP), 11β-OHP has been identified as a very potent competitive inhibitor of both isoforms (1 and 2) of 11β-hydroxysteroid dehydrogenase (11β-HSD).[4][5]
Outcome of 21-hydroxylase deficiency
It has been known since 1987 that increased levels of 11β-OHP occur in 21-hydroxylase deficiency.[6][7] A study in 2017 has shown that in subjects with 21-hydroxylase deficiency, serum 11β-OHP concentrations range from 0.012 to 3.37 ng/mL, while in control group it was below detection limit of 0.012 ng/mL.[8] 21-hydroxylase is an enzyme that is also involved in progesterone metabolism, producing 11-deoxycorticosterone. In normal conditions, 21-hydroxylase has higher activity on progesterone than steroid 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) that convert progesterone to 11β-OHP.[verification needed] That's why in 21-hydroxylase deficiency, given the normal function of the CYP11B enzymes, the progesterone is directed towards 11β-OHP pathway rather than towards 11-deoxycorticosterone pathway, that is also usually accompanied by an increase in progesterone levels.[9] In the normal route to aldosterone and cortisol, progesterone and 17α-hydroxyprogesterone are first hydroxylated at position 21 and then hydroxylated at other positions. In 21-hydroxylase deficiency, progesterone and 17α-hydroxyprogesterone accumulate and are the substrates of steroid 11β-hydroxylase, leading to 1β-OHP and 21-deoxycortisol, respectively.[10] In the 2017 study mentioned above, serum progesterone concentrations in boys (10 days to 18 years old) with 21-hydroxylase deficiency reached levels similar to female luteal values (up to 10.14 ng/mL, depending on severity and treatment), while in the control group of boys progesterone was 0.07 ng/mL (0.22 nmol/L) on average, ranged from 0.05 to 0.40 ng/mL.[8]
In a 2016 study, classical CAH patients receiving glucocorticoid therapy had C19 11-oxygenated steroid serum levels that were elevated 3-4 fold compared to healthy controls.[11] In that same study, the levels of C19 11-oxygenated androgens correlated positively with conventional androgens in women but negatively in men. The levels of 11KT were four times higher than that of T in women with the condition. In adult women with CAH, the ratio of DHT produced in a backdoor pathway to that produced in a conventional pathway increases as control of androgen excess by glucocorticoid therapy deteriorates.[12] In CAH patients with poor disease control, 11-oxygenated androgens remain elevated for longer than 17OHP, thus serving as a better biomarker for the effectiveness of the disease control.[13][14] In males with CAH, 11-oxygenated androgen levels may indicate the presence testicular adrenal rest tumors.[14][15][16]
While studies suggest that 11β-OHP, also known as 21-deoxycorticosterone, can be used as marker for adrenal 21-hydroxylase deficiency,[6] another 21-carbon steroid — 21-deoxycortisol (produced from 17α-hydroxyprogesterone) gained acceptance for this purpose.[17][18][19]
See also
- 21-Deoxycortisol (11β,17α-dihydroxyprogesterone)
- 11-Deoxycorticosterone (21-hydroxyprogesterone)
- Corticosterone (11β,21-dihydroxyprogesterone)
- Cortisol (11β,17α,21-trihydroxyprogesterone)
- 11-Deoxycortisol (17α,21-dihydroxyprogesterone)
- 9α-Bromo-11-ketoprogesterone
References
- ↑ 1.0 1.1 "Human Metabolome Database: Showing metabocard for 11b-Hydroxyprogesterone (HMDB04031)". hmdb.ca. http://www.hmdb.ca/metabolites/HMDB04031.
- ↑ 2.0 2.1 "Structural insights into aldosterone synthase substrate specificity and targeted inhibition". Molecular Endocrinology 27 (2): 315–24. February 2013. doi:10.1210/me.2012-1287. PMID 23322723.
- ↑ "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. April 2018. doi:10.1016/j.jsbmb.2017.12.014. PMID 29277707.
- ↑ "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat". Endocrinology 136 (4): 1809–12. April 1995. doi:10.1210/endo.136.4.7895695. PMID 7895695.
- ↑ "11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat". Hypertension 27 (3 Pt 1): 421–5. March 1996. doi:10.1161/01.hyp.27.3.421. PMID 8698448.
- ↑ 6.0 6.1 "The measurement of 11 beta-hydroxy-4-pregnene-3,20-dione (21-deoxycorticosterone) by radioimmunoassay in human plasma". Journal of Steroid Biochemistry 26 (1): 145–50. January 1987. doi:10.1016/0022-4731(87)90043-4. PMID 3546944.
- ↑ "Increased plasma 21-deoxycorticosterone (21-DB) levels in late-onset adrenal 21-hydroxylase deficiency suggest a mild defect of the mineralocorticoid pathway". The Journal of Clinical Endocrinology and Metabolism 68 (3): 542–7. March 1989. doi:10.1210/jcem-68-3-542. PMID 2537337.
- ↑ 8.0 8.1 "A Liquid Chromatography/Tandem Mass Spectometry [sic Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia"]. Journal of the Endocrine Society 1 (3): 186–201. March 2017. doi:10.1210/js.2016-1048. PMID 29264476.
- ↑ "[Possibility of progesterone as the diagnostic biomarker of 21-hydroxylase deficiency]". Zhonghua Yi Xue Za Zhi 96 (48): 3866–3869. December 2016. doi:10.3760/cma.j.issn.0376-2491.2016.48.003. PMID 28057154.
- ↑ "Adrenal steroidogenesis and congenital adrenal hyperplasia". Endocrinology and Metabolism Clinics of North America 44 (2): 275–96. June 2015. doi:10.1016/j.ecl.2015.02.002. PMID 26038201.
- ↑ "Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency". Eur J Endocrinol 174 (5): 601–9. 2016. doi:10.1530/EJE-15-1181. PMID 26865584.
- ↑ "Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency". J Clin Endocrinol Metab 99 (8): 2763–70. 2014. doi:10.1210/jc.2014-1258. PMID 24780050.
- ↑ "24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency". Front Endocrinol (Lausanne) 12: 751191. 2021. doi:10.3389/fendo.2021.751191. PMID 34867794.
- ↑ 14.0 14.1 "11-Oxygenated Androgens Are Biomarkers of Adrenal Volume and Testicular Adrenal Rest Tumors in 21-Hydroxylase Deficiency". The Journal of Clinical Endocrinology and Metabolism 102 (8): 2701–2710. 2017. doi:10.1210/jc.2016-3989. PMID 28472487.
- ↑ "Production of 11-Oxygenated Androgens by Testicular Adrenal Rest Tumors". J Clin Endocrinol Metab 107 (1): e272–e280. 2022. doi:10.1210/clinem/dgab598. PMID 34390337.
- ↑ "Alternative androgen pathways". WikiJournal of Medicine 10: X. 2023. doi:10.15347/WJM/2023.003.
- ↑ "Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation". Int J Neonatal Screen 9 (4): 58. October 2023. doi:10.3390/ijns9040058. PMID 37873849.
- ↑ "Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoring". Rapid Communications in Mass Spectrometry 18 (1): 77–82. 2004. doi:10.1002/rcm.1284. PMID 14689562. Bibcode: 2004RCMS...18...77C.
- ↑ "Utility of a Commercially Available Blood Steroid Profile in Endocrine Practice". Indian Journal of Endocrinology and Metabolism 23 (1): 97–101. 2019. doi:10.4103/ijem.IJEM_531_18. PMID 31016162.
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