17α-Hydroxyprogesterone

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17α-Hydroxyprogesterone
17-Hydroxyprogesterone.svg
17-Hidroxiprogesterona3D.png
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 (INN Tooltip International Nonproprietary Name)
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.636 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
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).

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.

Biological activity

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 100100100<1<1
17α-Hydroxyprogesterone1131<1
Hydroxyprogesterone caproate 2630284<1
Hydroxyprogesterone acetate 38461153?
Notes: Values are percentages (%). Reference ligands (100%) were progesterone for the PR Tooltip progesterone receptor, dexamethasone for the GR Tooltip glucocorticoid receptor, and estradiol for the ER Tooltip estrogen receptor. Sources: See template.

Biochemistry

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

Biosynthesis

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

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

Pharmacokinetics

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

Medical uses

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

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

Generic names

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

See also

References

  1. ↑ "17-hydroxyprogesterone (17OHP)".
  2. 1 2 3 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. 1 2 3 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. 1 2 3 Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 532–. ISBN   978-3-88763-075-1.
  5. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 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. 1 2 H. J. Smith, Hywel Williams (1 January 1983). Introduction to the Principles of Drug Design. Elsevier. pp. 187–. ISBN   978-1-4831-8350-3.
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