17α-Hydroxyprogesterone

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17α-Hydroxyprogesterone
17-Hydroxyprogesterone.svg
17-Hidroxiprogesterona3D.png
Names
Preferred 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
17α-Hydroxypregn-4-ene-3,20-dione, Hydroxyprogesterone (INN)
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.636 Edit this at Wikidata
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)C1(CCC2C1(CCC3C2CCC4=CC(=O)CCC34C)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).

17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone[1] (17-OHP),[2] or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone.[3][4][5] It is also a chemical intermediate in the biosynthesis of many other endogenous steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as neurosteroids.

Biological activity[edit]

17α-OHP is an agonist of the progesterone receptor (PR) similarly to progesterone, albeit weakly in comparison.[6] In addition, it is an antagonist of the mineralocorticoid receptor (MR)[7] 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.[6][8][9]

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 PR, dexamethasone for the GR, and estradiol for the ER. 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)[citation needed]

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

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.[10][11]

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. In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17α-OHP. 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.[citation needed]

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.[12][13]

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.[12][13]

Pharmacology[edit]

Pharmacokinetics[edit]

Although 17α-OHP has not been used as a medication, its pharmacokinetics have been studied and reviewed.[14]

Medical uses[edit]

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.[3][4][5] When "hydroxyprogesterone" is referenced from the standpoint of medical use, what is usually being referred to is actually, in general, hydroxyprogesterone caproate.[citation needed]

Chemistry[edit]

17α-OHP, also known as 17α-hydroxypregn-4-ene-3,20-dione, is a naturally occurring pregnane steroid. It features ketone groups at the C3 and C20 positions, a hydroxyl group at the C17α position, and a double bond between the C4 and C5 positions.[citation needed]

17α-OHP is the parent compound of a class of progestins referred to as the 17α-hydroxyprogesterone derivatives.[15][16][17] Among others, this class of drugs includes chlormadinone acetate, cyproterone acetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, and megestrol acetate.[15][16][17]

Society and culture[edit]

Generic names[edit]

Hydroxyprogesterone is the generic name of 17α-OHP and its INN and BAN.[3][4][5]

See also[edit]

References[edit]

  1. ^ "17-OH Progesterone Test". 15 August 2012.
  2. ^ "17-hydroxyprogesterone (17OHP)".
  3. ^ 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.
  4. ^ 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.
  5. ^ a b c Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 532–. ISBN 978-3-88763-075-1.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ Sun, Kang; Lei, Kaiyu; Chen, Li; Georgiou, Ektoras X.; Sooranna, Suren R.; Khanjani, Shirin; Brosens, Jan J.; Bennett, Phillip R.; Johnson, Mark R. (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.
  10. ^ Reference Values During Pregnancy
  11. ^ normal ranges for hormone tests in women
  12. ^ 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.
  13. ^ 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.
  14. ^ Die Gestagene. Springer-Verlag. 27 November 2013. pp. 276–277. ISBN 978-3-642-99941-3.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.