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5α-Dihydrolevonorgestrel Other names 5α-Dihydrolevonorgestrel; 5α-DHLNG; 5α-LNG
(5S ,8R ,9R ,10S ,13S ,14S ,17R )-13-Ethyl-17-ethynyl-17-hydroxy-1,2,4,5,6,7,8,9,10,11,12,14,15,16-tetradecahydrocyclopenta[a ]phenanthren-3-one
CAS Number PubChem CID ChemSpider UNII CompTox Dashboard (EPA ) Formula C 21 H 30 O 2 Molar mass 314.469 g·mol−1 3D model (JSmol )
CC[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CC[C@@H]4[C@@H]3CCC(=O)C4
InChI=1S/C21H30O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,14,16-19,23H,3,5-13H2,1H3/t14-,16-,17+,18+,19-,20-,21-/m0/s1
Key:BMVIRDJAPBCAPQ-WQGSDSCCSA-N
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 Tooltip estradiol (medication) ) 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]
Relative affinities (%) of levonorgestrel and metabolites
Compound
PR Tooltip Progesterone receptor
AR Tooltip Androgen receptor
ER Tooltip Estrogen receptor
GR Tooltip Glucocorticoid receptor
MR Tooltip Mineralocorticoid receptor
SHBG Tooltip Sex hormone-binding globulin
CBG Tooltip Corticosteroid binding globulin
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 Tooltip progesterone receptor , metribolone (a = mibolerone ) for the AR Tooltip androgen receptor , E2 for the ER Tooltip estrogen receptor , DEXA Tooltip dexamethasone for the GR Tooltip glucocorticoid receptor , aldosterone for the MR Tooltip mineralocorticoid receptor , DHT Tooltip dihydrotestosterone for SHBG Tooltip sex hormone-binding globulin , and cortisol for CBG Tooltip Corticosteroid-binding globulin . Sources: See template.
See also
References
^ a b Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF) . Climacteric . 8 Suppl 1: 3–63. doi :10.1080/13697130500148875 . PMID 16112947 .
^ Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (2008). "Classification and pharmacology of progestins". Maturitas . 61 (1–2): 171–80. doi :10.1016/j.maturitas.2008.11.013 . PMID 19434889 .
^ a b Vij U, Murugesan K, Kalita JC, Farooq A (February 1989). "Interaction of antiprogestins with progesterone receptors in rat uterus". J. Steroid Biochem . 32 (2): 279–82. doi :10.1016/0022-4731(89)90264-1 . PMID 2921869 .
^ a b c García-Becerra R, Borja-Cacho E, Cooney AJ, Jackson KJ, Lemus AE, Pérez-Palacios G, Larrea F (November 2002). "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. doi :10.1016/s0960-0760(02)00192-9 . PMID 12589940 .
^ Chu YH, Li QA, Zhao ZF, Zhou YP, Cao DC (1985). "[Antiprogestational action of 5 alpha-dihydronorethisterone]". Zhongguo Yao Li Xue Bao (in Chinese). 6 (2): 125–9. PMID 2934946 .
^ a b Cabeza M, Vilchis F, Lemus AE, Díaz de León L, Pérez-Palacios G (September 1995). "Molecular interactions of levonorgestrel and its 5 alpha-reduced derivative with androgen receptors in hamster flanking organs". Steroids . 60 (9): 630–5. doi :10.1016/0039-128X(95)00075-2 . PMID 8545853 .
^ Khan FS, Fotherby K (April 1979). "In vitro metabolism of 17 alpha-ethynylsteroids". J. Steroid Biochem . 10 (4): 437–42. doi :10.1016/0022-4731(79)90332-7 . PMID 449320 .
^ a b Santillán R, Pérez-Palacios G, Reyes M, Damián-Matsumura P, García GA, Grillasca I, Lemus AE (September 2001). "Assessment of the oestrogenic activity of the contraceptive progestin levonorgestrel and its non-phenolic metabolites". Eur. J. Pharmacol . 427 (2): 167–74. doi :10.1016/S0014-2999(01)01263-8 . PMID 11557270 .
AR Tooltip Androgen receptor
Agonists SARMs Tooltip Selective androgen receptor modulator Antagonists
GPRC6A
ER Tooltip Estrogen receptor
Agonists
Steroidal: 2-Hydroxyestradiol
2-Hydroxyestrone
3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol
3α-Androstanediol
3α,5α-Dihydrolevonorgestrel
3β,5α-Dihydrolevonorgestrel
3α-Hydroxytibolone
3β-Hydroxytibolone
3β-Androstanediol
4-Androstenediol
4-Androstenedione
4-Fluoroestradiol
4-Hydroxyestradiol
4-Hydroxyestrone
4-Methoxyestradiol
4-Methoxyestrone
5-Androstenediol
7-Oxo-DHEA
7α-Hydroxy-DHEA
7α-Methylestradiol
7β-Hydroxyepiandrosterone
8,9-Dehydroestradiol
8,9-Dehydroestrone
8β-VE2
10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED)
11β-Chloromethylestradiol
11β-Methoxyestradiol
15α-Hydroxyestradiol
16-Ketoestradiol
16-Ketoestrone
16α-Fluoroestradiol
16α-Hydroxy-DHEA
16α-Hydroxyestrone
16α-Iodoestradiol
16α-LE2
16β-Hydroxyestrone
16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
17α-Estradiol (alfatradiol )
17α-Dihydroequilenin
17α-Dihydroequilin
17α-Epiestriol (16α-hydroxy-17α-estradiol)
17α-Ethynyl-3α-androstanediol
17α-Ethynyl-3β-androstanediol
17β-Dihydroequilenin
17β-Dihydroequilin
17β-Methyl-17α-dihydroequilenin
Abiraterone
Abiraterone acetate
Alestramustine
Almestrone
Anabolic steroids (e.g., testosterone and esters , methyltestosterone , metandienone (methandrostenolone) , nandrolone and esters , many others; via estrogenic metabolites)
Atrimustine
Bolandiol
Bolandiol dipropionate
Butolame
Clomestrone
Cloxestradiol
Conjugated estriol
Conjugated estrogens
Cyclodiol
Cyclotriol
DHEA
DHEA-S
ent -Estradiol
Epiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol)
Epimestrol
Equilenin
Equilin
ERA-63 (ORG-37663)
Esterified estrogens
Estetrol
Estradiol
Estramustine
Estramustine phosphate
Estrapronicate
Estrazinol
Estriol
Estrofurate
Estrogenic substances
Estromustine
Estrone
Etamestrol (eptamestrol)
Ethinylandrostenediol
Ethinylestradiol
Ethinylestriol
Ethylestradiol
Etynodiol
Etynodiol diacetate
Hexolame
Hippulin
Hydroxyestrone diacetate
Lynestrenol
Lynestrenol phenylpropionate
Mestranol
Methylestradiol
Moxestrol
Mytatrienediol
Nilestriol
Norethisterone
Noretynodrel
Orestrate
Pentolame
Prodiame
Prolame
Promestriene
RU-16117
Quinestradol
Quinestrol
Tibolone
Xenoestrogens: Anise -related (e.g., anethole , anol , dianethole , dianol , photoanethole )
Chalconoids (e.g., isoliquiritigenin , phloretin , phlorizin (phloridzin) , wedelolactone )
Coumestans (e.g., coumestrol , psoralidin )
Flavonoids (incl. 7,8-DHF , 8-prenylnaringenin , apigenin , baicalein , baicalin , biochanin A , calycosin , catechin , daidzein , daidzin , ECG , EGCG , epicatechin , equol , formononetin , glabrene , glabridin , genistein , genistin , glycitein , kaempferol , liquiritigenin , mirificin , myricetin , naringenin , penduletin , pinocembrin , prunetin , puerarin , quercetin , tectoridin , tectorigenin )
Lavender oil
Lignans (e.g., enterodiol , enterolactone , nyasol (cis -hinokiresinol) )
Metalloestrogens (e.g., cadmium )
Pesticides (e.g., alternariol , dieldrin , endosulfan , fenarimol , HPTE , methiocarb , methoxychlor , triclocarban , triclosan )
Phytosteroids (e.g., digitoxin (digitalis ), diosgenin , guggulsterone )
Phytosterols (e.g., β-sitosterol , campesterol , stigmasterol )
Resorcylic acid lactones (e.g., zearalanone , α-zearalenol , β-zearalenol , zearalenone , zeranol (α-zearalanol) , taleranol (teranol, β-zearalanol) )
Steroid -like (e.g., deoxymiroestrol , miroestrol )
Stilbenoids (e.g., resveratrol , rhaponticin )
Synthetic xenoestrogens (e.g., alkylphenols , bisphenols (e.g., BPA , BPF , BPS ), DDT , parabens , PBBs , PHBA , phthalates , PCBs )
Others (e.g., agnuside , rotundifuran )
Mixed (SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
PR Tooltip Progesterone receptor
Agonists
Testosterone derivatives: Progestins: 6,6-Difluoronorethisterone
6,6-Difluoronorethisterone acetate
17α-Allyl-19-nortestosterone
Allylestrenol
Altrenogest
Chloroethynylnorgestrel
Cingestol
Danazol
Desogestrel
Dienogest
Ethinylandrostenediol
Ethisterone
Ethynerone
Etonogestrel
Etynodiol
Etynodiol diacetate
Gestodene
Gestrinone
Levonorgestrel
Levonorgestrel esters (e.g., levonorgestrel butanoate )
Lynestrenol
Lynestrenol phenylpropionate
Metynodiol
Metynodiol diacetate
Norelgestromin
Norethisterone (norethindrone)
Norethisterone esters (e.g., norethisterone acetate , norethisterone enanthate )
Noretynodrel
Norgesterone
Norgestimate
Norgestrel
Norgestrienone
Norvinisterone
Oxendolone
Quingestanol
Quingestanol acetate
Tibolone
Tigestol
Tosagestin ; Anabolic–androgenic steroids: 11β-Methyl-19-nortestosterone
11β-Methyl-19-nortestosterone dodecylcarbonate
19-Nor-5-androstenediol
19-Nor-5-androstenedione
19-Nordehydroepiandrosterone
Bolandiol
Bolandiol dipropionate
Bolandione
Dimethisterone
Dienedione
Dienolone
Dimethandrolone
Dimethandrolone buciclate
Dimethandrolone dodecylcarbonate
Dimethandrolone undecanoate
Dimethyldienolone
Dimethyltrienolone
Ethyldienolone
Ethylestrenol (ethylnandrol)
Methyldienolone
Metribolone (R-1881)
Methoxydienone (methoxygonadiene)
Mibolerone
Nandrolone
Nandrolone esters (e.g., nandrolone decanoate , nandrolone phenylpropionate )
Norethandrolone
Normethandrone (methylestrenolone, normethandrolone, normethisterone)
RU-2309
Tetrahydrogestrinone
Trenbolone (trienolone)
Trenbolone esters (e.g., trenbolone acetate , trenbolone enanthate )
Trendione
Trestolone
Trestolone acetate
Mixed (SPRMs Tooltip Selective progesterone receptor modulators ) Antagonists
mPR Tooltip Membrane progesterone receptor (PAQR Tooltip Progestin and adipoQ receptor )