20α-Dihydroprogesterone explained

20α-Dihydroprogesterone (20α-DHP), also known as 20α-hydroxyprogesterone (20α-OHP), is a naturally occurring, endogenous progestogen.[1] [2] [3] It is a metabolite of progesterone, formed by the 20α-hydroxysteroid dehydrogenases (20α-HSDs) AKR1C1, AKR1C2, and AKR1C3 and the 17β-hydroxysteroid dehydrogenase (17β-HSD) HSD17B1.[4] [5] 20α-DHP can be transformed back into progesterone by 20α-HSDs and by the 17β-HSD HSD17B2.[6] HSD17B2 is expressed in the human endometrium and cervix among other tissues.[7] [8] [9] In animal studies, 20α-DHP has been found to be selectively taken up into and retained in target tissues such as the uterus, brain, and skeletal muscle.

20α-DHP has very low affinity for the progesterone receptor and is much less potent as a progestogen in comparison to progesterone, with about one-fifth of the relative progestogenic activity.[10] [11] [12] [13] It has also been found to act as an aromatase inhibitor and to inhibit the production of estrogen in breast tissue in vitro.[14]

A single 200-mg oral dose of micronized progesterone has been found to result in peak levels of 20α-DHP of around 1 ng/mL after 2 hours.[15] In another study however, peak levels of 20α-DHP were around 10 ng/mL during therapy with 300 mg/day oral micronized progesterone.[16] 20α-DHP is formed from progesterone in the liver and in target tissues such as the endometrium. It appears to be more slowly eliminated than progesterone.

Levels of 5α-DHP have been quantified.[17]

See also

Notes and References

  1. Beranič N, Gobec S, Rižner TL . Progestins as inhibitors of the human 20-ketosteroid reductases, AKR1C1 and AKR1C3 . Chem. Biol. Interact. . 191 . 1–3 . 227–33 . 2011 . 21182831 . 10.1016/j.cbi.2010.12.012 .
  2. Book: Tony M. Plant. Anthony J. Zeleznik. Knobil and Neill's Physiology of Reproduction: Two-Volume Set. 15 November 2014. Academic Press. 978-0-12-397769-4. 1–.
  3. Book: Cynthia L. Darlington. The Female Brain. 27 April 2009. CRC Press. 978-1-4200-7745-2. 4–.
  4. Book: Marianne J. Legato. Principles of Gender-Specific Medicine. 29 October 2009. Academic Press. 978-0-08-092150-1. 617–.
  5. Rižner TL, Penning TM . Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism . Steroids . 79 . 49–63 . January 2014 . 24189185 . 3870468 . 10.1016/j.steroids.2013.10.012 .
  6. Book: Phung. Jason. Paul. Jonathan. Smith. Roger. Maternal-Fetal and Neonatal Endocrinology. Maintenance of Pregnancy and Parturition. 2020. 169–187. 10.1016/B978-0-12-814823-5.00013-1. 9780128148235. 208410112 .
  7. Casey ML, MacDonald PC, Andersson S . 17 beta-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium . J. Clin. Invest. . 94 . 5 . 2135–41 . November 1994 . 7962560 . 294662 . 10.1172/JCI117569 .
  8. Book: Lora Hedrick Ellenson. Molecular Genetics of Endometrial Carcinoma. 1 December 2016. Springer. 978-3-319-43139-0. 12–.
  9. Byrns MC . Regulation of progesterone signaling during pregnancy: implications for the use of progestins for the prevention of preterm birth . J. Steroid Biochem. Mol. Biol. . 139 . 173–81 . January 2014 . 23410596 . 10.1016/j.jsbmb.2013.01.015 . 23414730 .
  10. Book: Bertram G. Katzung. Basic and Clinical Pharmacology 14th Edition. 30 November 2017. McGraw-Hill Education. 978-1-259-64116-9. 728. In addition to progesterone, 20α- and 20β-hydroxyprogesterone (20α- and 20β-hydroxy-4-pregnene-3-one) also are found. These compounds have about one-fifth the progestational activity of progesterone in humans and other species..
  11. Ogle TF, Beyer BK . Steroid-binding specificity of the progesterone receptor from rat placenta . J. Steroid Biochem. . 16 . 2 . 147–50 . February 1982 . 7078152 . 10.1016/0022-4731(82)90160-1 .
  12. Nowak FV . Distribution and metabolism of 20 alpha-hydroxylated progestins in the female rat . J. Steroid Biochem. Mol. Biol. . 80 . 4–5 . 469–79 . April 2002 . 11983494 . 10.1016/S0960-0760(02)00039-0 . 54366844 .
  13. Zander J, Forbes TR, Von Munstermann AM, Neher R . Delta 4-3-Ketopregnene-20 alpha-ol and delta 4-3-ketopregnene-20 beta-ol, two naturally occurring metabolites of progesterone; isolation, identification, biologic activity and concentration in human tissues . J. Clin. Endocrinol. Metab. . 18 . 4 . 337–53 . April 1958 . 13513735 . 10.1210/jcem-18-4-337 . free .
  14. Pasqualini JR, Chetrite G . The anti-aromatase effect of progesterone and of its natural metabolites 20alpha- and 5alpha-dihydroprogesterone in the MCF-7aro breast cancer cell line . Anticancer Res. . 28 . 4B . 2129–33 . 2008 . 18751385 .
  15. Sitruk-Ware R, Bricaire C, De Lignieres B, Yaneva H, Mauvais-Jarvis P . Oral micronized progesterone. Bioavailability pharmacokinetics, pharmacological and therapeutic implications--a review . Contraception . 36 . 4 . 373–402 . October 1987 . 3327648 . 10.1016/0010-7824(87)90088-6 .
  16. Padwick ML, Endacott J, Matson C, Whitehead MI . Absorption and metabolism of oral progesterone when administered twice daily . Fertil. Steril. . 46 . 3 . 402–7 . September 1986 . 3743792 . 10.1016/S0015-0282(16)49576-2 .
  17. Trabert B, Falk RT, Stanczyk FZ, McGlynn KA, Brinton LA, Xu X . Reproducibility of an assay to measure serum progesterone metabolites that may be related to breast cancer risk using liquid chromatography-tandem mass spectrometry . Horm Mol Biol Clin Investig . 23 . 3 . 79–84 . September 2015 . 26353176 . 4966666 . 10.1515/hmbci-2015-0026 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "20α-Dihydroprogesterone".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.