Chemistry:5α-Dihydrolevonorgestrel
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| Other names | 5α-Dihydrolevonorgestrel; 5α-DHLNG; 5α-LNG |
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| Formula | C21H30O2 |
| Molar mass | 314.469 g·mol−1 |
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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.[1] 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.[3][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.[6] 5α-DHLNG is further transformed into 3α,5α- and 3β,5α-THLNG, which bind weakly to the estrogen receptor (0.4 to 2.4% of the RBA of E2) and have weak estrogenic activity.[7][8][4] These metabolites are considered to be responsible for the weak estrogenic activity of high doses of levonorgestrel.[8][4]
| Compound | PR | AR | ER | GR | MR | SHBG | CBG |
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| Levonorgestrel | 150–162 | 34a, 45 | 0 | 1–8 | 17–75 | 50 | 0 |
| 5α-Dihydrolevonorgestrel | 50 | 38a | 0 | ? | ? | ? | ? |
| 3α,5α-Tetrahydrolevonorgestrel | ? | ? | 0.4 | ? | ? | ? | ? |
| 3β,5α-Tetrahydrolevonorgestrel | ? | ? | 2.4 | ? | ? | ? | ? |
| Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PR, metribolone (a = mibolerone) for the AR, E2 for the ER, DEXA for the GR, aldosterone for the MR, DHT for SHBG, and cortisol for CBG. Sources: See template. | |||||||
See also
References
- ↑ 1.0 1.1 "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric 8 (Suppl 1): 3–63. 2005. doi:10.1080/13697130500148875. PMID 16112947. http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf.
- ↑ "Classification and pharmacology of progestins". Maturitas 61 (1–2): 171–80. 2008. doi:10.1016/j.maturitas.2008.11.013. PMID 19434889.
- ↑ 3.0 3.1 "Interaction of antiprogestins with progesterone receptors in rat uterus". J. Steroid Biochem. 32 (2): 279–82. February 1989. doi:10.1016/0022-4731(89)90264-1. PMID 2921869.
- ↑ 4.0 4.1 4.2 "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. doi:10.1016/s0960-0760(02)00192-9. PMID 12589940.
- ↑ "[Antiprogestational action of 5 alpha-dihydronorethisterone]" (in zh). Zhongguo Yao Li Xue Bao 6 (2): 125–9. 1985. PMID 2934946.
- ↑ 6.0 6.1 "Molecular interactions of levonorgestrel and its 5 alpha-reduced derivative with androgen receptors in hamster flanking organs". Steroids 60 (9): 630–5. September 1995. doi:10.1016/0039-128X(95)00075-2. PMID 8545853.
- ↑ "In vitro metabolism of 17 alpha-ethynylsteroids". J. Steroid Biochem. 10 (4): 437–42. April 1979. doi:10.1016/0022-4731(79)90332-7. PMID 449320.
- ↑ 8.0 8.1 "Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites". Eur. J. Pharmacol. 427 (2): 167–74. September 2001. doi:10.1016/S0014-2999(01)01263-8. PMID 11557270.
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