Wikipedia

17α-Hydroxyprogesterone

"Hydroxyprogesterone" redirects here. For other uses, see Hydroxyprogesterone (disambiguation).
Not to be confused with Hydroxyprogesterone caproate or Hydroxyprogesterone acetate.

17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP),[1] or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone.[2][3][4] It is also a chemical intermediate in the biosynthesis of many other endogenous steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as neurosteroids.

17α-Hydroxyprogesterone
Names
IUPAC name
17α-Hydroxypregn-4-ene-3,20-dione
Systematic IUPAC name
(1R,3aS,3bR,9aR,9bS,11aS)-1-Acetyl-1-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
Hydroxyprogesterone (INNTooltip International Nonproprietary Name)
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.636 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C21H30O3/c1-13(22)21(24)11-8-18-16-5-4-14-12-15(23)6-9-19(14,2)17(16)7-10-20(18,21)3/h12,16-18,24H,4-11H2,1-3H3/t16-,17+,18+,19+,20+,21+/m1/s1
    Key: DBPWSSGDRRHUNT-CEGNMAFCSA-N
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)C)O
Properties
C21H30O3
Molar mass 330.46 g/mol
Melting point 219.5
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Biological activity

edit

17α-OHP is an agonist of the progesterone receptor (PR) similarly to progesterone, albeit weakly in comparison.[5] In addition, it is an antagonist of the mineralocorticoid receptor (MR)[6] as well as a partial agonist of the glucocorticoid receptor (GR), albeit with very low potency (EC50 >100-fold less relative to cortisol) at the latter site, also similarly to progesterone.[5][7][8]

Relative affinities (%) of hydroxyprogesterone and related steroids
Compound hPR-A hPR-B rbPR rbGR rbER
Progesterone 100 100 100 <1 <1
17α-Hydroxyprogesterone 1 1 3 1 <1
Hydroxyprogesterone caproate 26 30 28 4 <1
Hydroxyprogesterone acetate 38 46 115 3 ?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PRTooltip progesterone receptor, dexamethasone for the GRTooltip glucocorticoid receptor, and estradiol for the ERTooltip estrogen receptor. Sources: See template.

Biochemistry

edit
 
Steroidogenesis, showing 17α-OHP around the left-middle among the pregnenes.

Biosynthesis

edit

17α-OHP is derived from progesterone via 17α-hydroxylase (encoded by CYP17A1).[9]

17α-OHP increases in the third trimester of pregnancy primarily due to fetal adrenal production.[10]

This steroid is primarily produced in the adrenal glands and to some degree in the gonads, specifically the corpus luteum of the ovary. Normal levels are 3-90 ng/dl in children, and in women, 20-100 ng/dl prior to ovulation, and 100-500 ng/dl during the luteal phase.[11][12]

Measurement

edit

Measurements of levels of 17α-OHP are useful in the evaluation of patients with suspected congenital adrenal hyperplasia as the typical enzymes that are defective, namely 21-hydroxylase and 11β-hydroxylase, lead to a build-up of 17α-OHP.[13] In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17α-OHP.[9] 17α-OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but note, 17α-OHP is also contributed by the placenta.[14]

Immunoassays like RIA (radioimmunoassay) or IRMA (immunoradiometric assay) used to clinically determine 17α-OHP are prone to cross-reactivity with the 17α-OHP steroid precursors and their sulphated conjugates. Gas or liquid chromatography and mass spectrometry (e.g. LC-MS/MS) achieves greater specificity than immunoassays.[15][16]

Measurement of 17α-OHP by LC-MS/MS improves newborn screening for congenital adrenal hyperplasia due to 21-hydroxylase deficiency, because 17α-OHP steroid precursors and their sulphated conjugates which are present in the first two days after birth and longer in pre-term neonates, cross-react in immunoassays with 17α-OHP, giving falsely high 17α-OHP levels.[15][16]

Pharmacology

edit

Pharmacokinetics

edit

Although 17α-OHP has not been used as a medication, its pharmacokinetics have been studied and reviewed.[17]

Medical uses

edit
See also: Hydroxyprogesterone caproate, Hydroxyprogesterone acetate, and Hydroxyprogesterone heptanoate

Esters of 17α-OHP, such as hydroxyprogesterone caproate and, to a far lesser extent, hydroxyprogesterone acetate and hydroxyprogesterone heptanoate, have been used in medicine as progestins.[2][3][4]

Chemistry

edit
See also: List of progestogens

17α-OHP is the parent compound of a class of progestins referred to as the 17α-hydroxyprogesterone derivatives.[18][19][20] Among others, this class of drugs includes chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.[18][19][20]

Society and culture

edit

Generic names

edit

Hydroxyprogesterone is the generic name of 17α-OHP and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name.[2][3][4]

See also

edit

References

edit
  1. ^ "17-hydroxyprogesterone (17OHP)".
  2. ^ a b c J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 664–665. ISBN 978-1-4757-2085-3.
  3. ^ a b c I.K. Morton, Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 146–. ISBN 978-94-011-4439-1.
  4. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 532–. ISBN 978-3-88763-075-1.
  5. ^ a b Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN (2007). "Comparison of progesterone and glucocorticoid receptor binding and stimulation of gene expression by progesterone, 17-alpha hydroxyprogesterone caproate, and related progestins". Am. J. Obstet. Gynecol. 197 (6): 599.e1–7. doi:10.1016/j.ajog.2007.05.024. PMC 2278032. PMID 18060946.
  6. ^ Mooij CF, Parajes S, Pijnenburg-Kleizen KJ, Arlt W, Krone N, Claahsen-van der Grinten HL (April 2015). "Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia" (PDF). Horm Res Paediatr. 83 (6): 414–421. doi:10.1159/000374112. PMID 25896481. S2CID 24727940.
  7. ^ Pijnenburg-Kleizen KJ, Engels M, Mooij CF, Griffin A, Krone N, Span PN, van Herwaarden AE, Sweep FC, Claahsen-van der Grinten HL (2015). "Adrenal Steroid Metabolites Accumulating in Congenital Adrenal Hyperplasia lead to Transactivation of the Glucocorticoid Receptor". Endocrinology. 156 (10): 3504–3510. doi:10.1210/en.2015-1087. PMID 26207344.
  8. ^ Sun K, Lei K, Chen L, Georgiou EX, Sooranna SR, Khanjani S, Brosens JJ, Bennett PR, Johnson MR (2012). "Progesterone Acts via the Nuclear Glucocorticoid Receptor to Suppress IL-1β-Induced COX-2 Expression in Human Term Myometrial Cells". PLOS ONE. 7 (11): e50167. Bibcode:2012PLoSO...750167L. doi:10.1371/journal.pone.0050167. ISSN 1932-6203. PMC 3509141. PMID 23209664.
  9. ^ a b Kim SM, Rhee JH (2015). "A case of 17 alpha-hydroxylase deficiency". Clinical and Experimental Reproductive Medicine. 42 (2). The Korean Society for Reproductive Medicine: 72–76. doi:10.5653/cerm.2015.42.2.72. ISSN 2233-8233. PMC 4496435. PMID 26161337.
  10. ^ Tal R, Taylor HS (2021-03-18). "Endocrinology of Pregnancy". MDText.com, Inc. PMID 25905197. Retrieved 2024-06-25.
  11. ^ Reference Values During Pregnancy
  12. ^ "normal ranges for hormone tests in women". Archived from the original on 2020-11-08. Retrieved 2011-08-07.
  13. ^ Held PK, Bird IM, Heather NL (2020-08-23). "Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy". International Journal of Neonatal Screening. 6 (3). MDPI AG: 67. doi:10.3390/ijns6030067. ISSN 2409-515X. PMC 7569755. PMID 33117906.
  14. ^ Check JH, Vaze MM, Epstein R, Wu CH, Quattrocchi J, Vetter B (1990). "17-Hydroxyprogesterone level as a marker for corpus luteum function in aborters versus nonaborters". International Journal of Fertility. 35 (2): 112–115. ISSN 0020-725X. PMID 1970979.
  15. ^ a b de Hora MR, Heather NL, Patel T, Bresnahan LG, Webster D, Hofman PL (March 2020). "Measurement of 17-Hydroxyprogesterone by LCMSMS Improves Newborn Screening for CAH Due to 21-Hydroxylase Deficiency in New Zealand". International Journal of Neonatal Screening. 6 (1): 6. doi:10.3390/ijns6010006. PMC 7422986. PMID 33073005.
  16. ^ a b Bialk ER, Lasarev MR, Held PK (September 2019). "Wisconsin's Screening Algorithm for the Identification of Newborns with Congenital Adrenal Hyperplasia". International Journal of Neonatal Screening. 5 (3): 33. doi:10.3390/ijns5030033. PMC 7510207. PMID 33072992.
  17. ^ Die Gestagene. Springer-Verlag. 27 November 2013. pp. 276–277. ISBN 978-3-642-99941-3.
  18. ^ a b Jeffrey K. Aronson (21 February 2009). Meyler's Side Effects of Endocrine and Metabolic Drugs. Elsevier. pp. 289–. ISBN 978-0-08-093292-7.
  19. ^ a b Robert Alan Prentky, Ann Wolbert Burgess (31 July 2000). Forensic Management of Sexual Offenders. Springer Science & Business Media. pp. 219–. ISBN 978-0-306-46278-8.
  20. ^ a b H. J. Smith, Hywel Williams (1 January 1983). Introduction to the Principles of Drug Design. Elsevier. pp. 187–. ISBN 978-1-4831-8350-3.
Retrieved from "https://en.wikipedia.org/w/index.php?title=17α-Hydroxyprogesterone&oldid=1233114553"
pFad - Phonifier reborn

Pfad - The Proxy pFad of © 2024 Garber Painting. All rights reserved.

Note: This service is not intended for secure transactions such as banking, social media, email, or purchasing. Use at your own risk. We assume no liability whatsoever for broken pages.


Alternative Proxies:

Alternative Proxy

pFad Proxy

pFad v3 Proxy

pFad v4 Proxy