5α-Dihydrolevonorgestrel explained

5α-Dihydrolevonorgestrel (5α-DHLNG) is an active metabolite of the progestin levonorgestrel which is formed by 5α-reductase.^{[1] [2]} It has about one-third of the affinity of levonorgestrel for the progesterone receptor. In contrast to levonorgestrel, the compound has both progestogenic and antiprogestogenic activity, and hence has a selective progesterone receptor modulator-like profile of activity.^{[3] [4]} This is analogous to the case of norethisterone and 5α-dihydronorethisterone.^[5] In addition to the progesterone receptor, 5α-DHLNG interacts with the androgen receptor.^[6] It has similar affinity for the androgen receptor relative to levonorgestrel (34.3% of that of metribolone for levonorgestrel and 38.0% of that of metribolone for 5α-DHLNG), and has androgenic effects similarly to levonorgestrel and testosterone. 5α-DHLNG is further transformed into 3α,5α- and 3β,5α-, which bind weakly to the estrogen receptor (0.4 to 2.4% of the of) and have weak estrogenic activity.^{[7] [8]} These metabolites are considered to be responsible for the weak estrogenic activity of high doses of levonorgestrel.

See also

• 5α-Dihydronorethisterone
• 5α-Dihydroethisterone
• 5α-Dihydronandrolone
• 5α-Dihydronormethandrone

Notes and References

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2. Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH . Classification and pharmacology of progestins . Maturitas . 61 . 1–2 . 171–80 . 2008 . 19434889 . 10.1016/j.maturitas.2008.11.013.
3. Vij U, Murugesan K, Kalita JC, Farooq A . Interaction of antiprogestins with progesterone receptors in rat uterus . J. Steroid Biochem. . 32 . 2 . 279–82 . February 1989 . 2921869 . 10.1016/0022-4731(89)90264-1.
4. García-Becerra R, Borja-Cacho E, Cooney AJ, Jackson KJ, Lemus AE, Pérez-Palacios G, Larrea F . The intrinsic transcriptional estrogenic activity of a non-phenolic derivative of levonorgestrel is mediated via the estrogen receptor-alpha . J. Steroid Biochem. Mol. Biol. . 82 . 4–5 . 333–41 . November 2002 . 12589940 . 10.1016/s0960-0760(02)00192-9. 24204715 .
5. Chu YH, Li QA, Zhao ZF, Zhou YP, Cao DC . [Antiprogestational action of 5 alpha-dihydronorethisterone] . zh . Zhongguo Yao Li Xue Bao . 6 . 2 . 125–9 . 1985 . 2934946 .
6. Cabeza M, Vilchis F, Lemus AE, Díaz de León L, Pérez-Palacios G . Molecular interactions of levonorgestrel and its 5 alpha-reduced derivative with androgen receptors in hamster flanking organs . Steroids . 60 . 9 . 630–5 . September 1995 . 8545853 . 10.1016/0039-128X(95)00075-2 . 20869899 .
7. Khan FS, Fotherby K . In vitro metabolism of 17 alpha-ethynylsteroids . J. Steroid Biochem. . 10 . 4 . 437–42 . April 1979 . 449320 . 10.1016/0022-4731(79)90332-7.
8. Santillán R, Pérez-Palacios G, Reyes M, Damián-Matsumura P, García GA, Grillasca I, Lemus AE . Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites . Eur. J. Pharmacol. . 427 . 2 . 167–74 . September 2001 . 11557270 . 10.1016/S0014-2999(01)01263-8 .