Retroprogesterone Explained

Retroprogesterone, also known as 9β,10α-progesterone or as 9β,10α-pregn-4-ene-3,20-dione, is a progestin which was never marketed.^{[1] [2]} It is a stereoisomer of the naturally occurring progestogen progesterone, in which the hydrogen atom at the 9th carbon is in the α-position (below the plane) instead of the β-position (above the plane) and the methyl group at the 10th carbon is in the β-position instead of the α-position. In other words, the atom positions at the two carbons have been reversed relative to progesterone, hence the name retroprogesterone. This reversal results in a "bent" configuration in which the plane of rings A and B is orientated at a 60° angle below the rings C and D.^[3] This configuration is ideal for interaction with the progesterone receptor, with retroprogesterone binding with high affinity to this receptor.^[4] However, the configuration is not as ideal for binding to other steroid hormone receptors, and as a result, retroprogesterone derivatives have increased selectivity for the progesterone receptor relative to progesterone.^[5]

Retroprogesterone is the parent compound of a group of progestins consisting of the marketed progestins dydrogesterone (6-dehydroretroprogesterone) and trengestone (1,6-didehydro-6-chlororetroprogesterone) and the never-marketed progestin Ro 6-3129, as well as the active metabolites of these progestins like 20α-dihydrodydrogesterone and 20α-dihydrotrengestone (i.e., the 20α-hydroxylated analogues).^{[6] [7]}

Chemistry

See also: List of progestogens.

See also

• 17α-Hydroxyprogesterone
• 19-Norprogesterone
• 17α-Ethynyltestosterone
• 19-Nortestosterone
• 17α-Spirolactone

Notes and References

1. Book: Horský J . Therapy of Anovolution . Horský J, Presl J . Ovarian Function and its Disorders: Diagnosis and Therapy. https://books.google.com/books?id=7IrpCAAAQBAJ&pg=PA329. 6 December 2012. Springer Science & Business Media. 978-94-009-8195-9. 305, 329.
2. Book: Sindhu SG . Endometrial Receptivity and Luteal Support . Talwar P, Sindhu SG . Step by Step: Protocols in Clinical Embryology and ART . https://books.google.com/books?id=KOP17hRq_YgC&pg=PA379 . 18 May 2012. JP Medical Ltd. 978-93-5025-765-4. 379–.
3. Kuhl H . Pharmacology of estrogens and progestogens: influence of different routes of administration . Climacteric . 8 . Suppl 1 . 3–63 . August 2005 . 16112947 . 10.1080/13697130500148875 . 24616324 .
4. Book: Litwack G . Biochemical Actions of Hormones. 2 December 2012. Elsevier. 978-0-323-15189-4. 193–.
5. Rižner TL, Brožič P, Doucette C, Turek-Etienne T, Müller-Vieira U, Sonneveld E, van der Burg B, Böcker C, Husen B . 6 . Selectivity and potency of the retroprogesterone dydrogesterone in vitro . Steroids . 76 . 6 . 607–615 . May 2011 . 21376746 . 10.1016/j.steroids.2011.02.043 . 31609405 .
6. Book: Padubidri VG, Anand E . Hormonal Therapy in Gynecology . Gynaecology. https://books.google.com/books?id=6mvbRMT3_eoC&pg=PA207. January 2005. Elsevier India. 978-81-8147-562-6. 207–.
7. Dixon R, Hudson S, Darragh A . Pharmacokinetics of the retro-steroid progestogen, 16α-ethylthio-9β,10α-pregna-4, 6-diene-3, 20-dione (Ro 6-3129), in man and the sheep. Contraception. 8. 1. 1973. 53–65. 0010-7824. 10.1016/0010-7824(73)90159-5.