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====Aktivitas androgenik====
Norethisterone memiliki sekitar 15% afinitas metribolon steroid anabolik-androgenik (AAS) (R-1881) untuk AR, dan karenanya, bersifat androgenik lemah.<ref name="pmid16112947" /> Berbeda dengan norethisterone, 5α-DHNET, metabolit utama norethisterone, menunjukkan afinitas yang lebih tinggi terhadap AR, dengan sekitar 27% afinitas terhadap metribolon.<ref name="pmid16112947" /> Namun, meskipun 5α-DHNET memiliki afinitas yang lebih tinggi terhadap AR dibandingkan norethisterone, ia telah berkurang secara signifikan dan bahkan hampir menghilangkan potensi androgenik dibandingkan dengan norethisterone dalam bioassay[[bioasai]] [[hewan pengerat]].<ref name="pmid19028512">{{cite journal | vauthors = Fragkaki AG, Angelis YS, Koupparis M, Tsantili-Kakoulidou A, Kokotos G, Georgakopoulos C | title = Structural characteristics of anabolic androgenic steroids contributing to binding to the androgen receptor and to their anabolic and androgenic activities. Applied modifications in the steroidal structure | journal = Steroids | volume = 74 | issue = 2 | pages = 172–97 | date = February 2009 | pmid = 19028512 | doi = 10.1016/j.steroids.2008.10.016 | quote = Many synthetic steroids with high myotrophic activity exhibit myotrophic–androgenic dissociation, since, due to changes introduced in the structure of ring A, they will probably not be substrates for the 5α-reductases [85]. 5α-Reduction does not always amplify the androgenic potency in spite of high RBA of androgens to the AR. This is the case for norethisterone (Fig. 1, 34), a synthetic 19-nor-17α-ethynyl testosterone derivative, which also undergoes enzyme-mediated 5α-reduction and exerts potent androgenic effects in target organs. 5α-Reduced norethisterone displays a higher AR binding but shows a significantly lower androgenic potency than unchanged norethisterone [102,103]. | s2cid = 41356223 }}</ref><ref name="pmid9182866">{{cite journal | vauthors = Lemus AE, Enríquez J, García GA, Grillasca I, Pérez-Palacios G | title = 5alpha-reduction of norethisterone enhances its binding affinity for androgen receptors but diminishes its androgenic potency | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 60 | issue = 1–2 | pages = 121–9 | date = January 1997 | pmid = 9182866 | doi = 10.1016/s0960-0760(96)00172-0 | s2cid = 33771349 }}</ref> Temuan serupa diamati untuk ethisterone (17α-ethynyltestosterone) dan metabolitnya yang tereduksi 5α, sedangkan reduksi 5α meningkatkan afinitas AR dan potensi androgenik testosteron dan nandrolone (19-nortestosteron) dalam bioassaybioasai hewan pengerat.<ref name="pmid9182866" /> Dengan demikian, nampaknya gugus etinil norethisterone pada posisi C17α bertanggung jawab atas hilangnya androgenisitasnya pada reduksi 5α.[54]<ref name="pmid9182866" />
Norethisterone (0,5 hingga 3 mg/hari) terbukti menurunkan kadar SHBG dalam sirkulasi secara ketergantungan dosis, yang merupakan sifat umum androgen dan disebabkan oleh penekanan produksi SHBG hati yang dimediasi oleh AR.[38] Obat ini juga mempunyai aktivitas estrogenik, dan estrogen diketahui meningkatkan produksi SHBG di hati dan kadar sirkulasi, sehingga aktivitas androgenik norethisterone mengalahkan aktivitas estrogeniknya dalam hal ini.[38]<ref name="pmid9494772">{{cite journal | vauthors = Kuhnz W, Heuner A, Hümpel M, Seifert W, Michaelis K | title = In vivo conversion of norethisterone and norethisterone acetate to ethinyl etradiol in postmenopausal women | journal = Contraception | volume = 56 | issue = 6 | pages = 379–85 | date = December 1997 | pmid = 9494772 | doi = 10.1016/s0010-7824(97)00174-1 }}</ref>
Norethisterone terikat sebagian besar (36%) pada SHBG yang beredar.[3]<ref name="pmid16112947" /> Meskipun memiliki afinitas yang lebih rendah terhadap SHBG dibandingkan androgen dan estrogen endogen,<ref name="FilshieGuillebaud2013">{{cite book| vauthors = Filshie M, Guillebaud J |title=Contraception: Science and Practice|url=https://books.google.com/books?id=Ug3-BAAAQBAJ&pg=PA26|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4831-6366-6|pages=26–|quote=Norethisterone binds to SHBG with less affinity than endogenous androgens and oestrogens [55...]}}</ref> Norethisterone dapat menggantikan testosteron dari SHBG dan dengan demikian meningkatkan kadar testosteron bebas, dan tindakan ini mungkin berkontribusi terhadap efek androgeniknya yang lemah.[56]<ref name="Azziz2007">{{cite book| vauthors = Azziz R |title=Androgen Excess Disorders in Women|url=https://books.google.com/books?id=Ch-BsGAOtucC&pg=PA124|date=8 November 2007|publisher=Springer Science & Business Media|isbn=978-1-59745-179-6|pages=124–}}</ref>
====Aktivitas estrogenik====
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