17α-Hydroxyprogesterone explained

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.[7] [8]

Biochemistry

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 (immunoradiometricassay) 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

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.

Chemistry

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.

Society and culture

Generic names

Hydroxyprogesterone is the generic name of 17α-OHP and its and .

See also

Notes and References

  1. Web site: 17-hydroxyprogesterone (17OHP).
  2. Book: J. Elks. The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. 14 November 2014. Springer. 978-1-4757-2085-3. 664–665.
  3. Book: I.K. Morton. Judith M. Hall. Concise Dictionary of Pharmacological Agents: Properties and Synonyms. 6 December 2012. Springer Science & Business Media. 978-94-011-4439-1. 146–.
  4. Book: Index Nominum 2000: International Drug Directory. January 2000. Taylor & Francis. 978-3-88763-075-1. 532–.
  5. Attardi BJ, Zeleznik A, Simhan H, Chiao JP, Mattison DR, Caritis SN . 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 . 2007 . 18060946 . 2278032 . 10.1016/j.ajog.2007.05.024 .
  6. Mooij CF, Parajes S, Pijnenburg-Kleizen KJ, Arlt W, Krone N, Claahsen-van der Grinten HL . Influence of 17-Hydroxyprogesterone, Progesterone and Sex Steroids on Mineralocorticoid Receptor Transactivation in Congenital Adrenal Hyperplasia . Horm Res Paediatr . 83. 6. 414–421. April 2015 . 25896481 . 10.1159/000374112 . 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 . Adrenal Steroid Metabolites Accumulating in Congenital Adrenal Hyperplasia lead to Transactivation of the Glucocorticoid Receptor . Endocrinology . 156. 10. 3504–3510 . 2015 . 26207344 . 10.1210/en.2015-1087 . free .
  8. Sun. Kang. Lei. Kaiyu. Chen. Li. Georgiou. Ektoras X.. Sooranna. Suren R.. Khanjani. Shirin. Brosens. Jan J.. Bennett. Phillip R.. Johnson. Mark R.. Progesterone Acts via the Nuclear Glucocorticoid Receptor to Suppress IL-1β-Induced COX-2 Expression in Human Term Myometrial Cells. PLOS ONE. 7. 11. 2012. e50167. 1932-6203. 10.1371/journal.pone.0050167. 23209664. 3509141. 2012PLoSO...750167L. free.
  9. Kim . Sung Mee . Rhee . Jeong Ho . A case of 17 alpha-hydroxylase deficiency . Clinical and Experimental Reproductive Medicine . The Korean Society for Reproductive Medicine . 42 . 2 . 2015 . 72–76 . 2233-8233 . 10.5653/cerm.2015.42.2.72 . 26161337 . 4496435 .
  10. Web site: Tal . Reshef . Taylor . Hugh S. . Endocrinology of Pregnancy . MDText.com, Inc. . 2021-03-18 . 25905197 . 2024-06-25.
  11. http://www.perinatology.com/Reference/Reference%20Ranges/17-hydroxyprogesterone.htm Reference Values During Pregnancy
  12. Web site: normal ranges for hormone tests in women . 2011-08-07 . 2020-11-08 . https://web.archive.org/web/20201108215852/https://www.keratin.com/ab/ab012.shtml . dead .
  13. Held . Patrice K. . Bird . Ian M. . Heather . Natasha L. . Newborn Screening for Congenital Adrenal Hyperplasia: Review of Factors Affecting Screening Accuracy . International Journal of Neonatal Screening . MDPI AG . 6 . 3 . 2020-08-23 . 2409-515X . 10.3390/ijns6030067 . free . 67. 33117906 . 7569755 .
  14. Check . J. H. . Vaze . M. M. . Epstein . R. . Wu . C. H. . Quattrocchi . J. . Vetter . B. . 17-Hydroxyprogesterone level as a marker for corpus luteum function in aborters versus nonaborters . International Journal of Fertility . 35 . 2 . 1990 . 0020-725X . 1970979 . 112–115.
  15. de Hora MR, Heather NL, Patel T, Bresnahan LG, Webster D, Hofman PL . 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 . March 2020 . 33073005 . 7422986 . 10.3390/ijns6010006. free .
  16. Bialk ER, Lasarev MR, Held PK . Wisconsin's Screening Algorithm for the Identification of Newborns with Congenital Adrenal Hyperplasia . International Journal of Neonatal Screening . 5 . 3 . 33 . September 2019 . 33072992 . 7510207 . 10.3390/ijns5030033. free .
  17. Book: Die Gestagene. 27 November 2013. Springer-Verlag. 978-3-642-99941-3. 276–277.
  18. Book: Jeffrey K. Aronson. Meyler's Side Effects of Endocrine and Metabolic Drugs. 21 February 2009. Elsevier. 978-0-08-093292-7. 289–.
  19. Book: Robert Alan Prentky. Ann Wolbert Burgess. Forensic Management of Sexual Offenders. 31 July 2000. Springer Science & Business Media. 978-0-306-46278-8. 219–.
  20. Book: H. J. Smith. Hywel Williams. Introduction to the Principles of Drug Design. 1 January 1983. Elsevier. 978-1-4831-8350-3. 187–.

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