Oropeza M V, Campos M G, Lemus A E, Garciá G, Pérez-Palacios G, Ponce-Monter H
UIM en Farmacología, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, IMSS, México, D.F.
Arch Med Res. 1994 Autumn;25(3):307-10.
The estrogen-like effects of norethisterone (NET) seem to be mediated by the interaction of 3 beta 5 alpha- and 3 alpha 5 alpha-tetrahydronorethisterone (3 beta 5 alpha- and 3 alpha 5 alpha-NET, respectively) with the estrogen receptor. Considering that the in vitro uterine contractile response to serotonin (5-HT) is specifically dependent on estrogen, the aim of the present study was to investigate whether NET and its A-ring reduced metabolites administered in vivo to ovariectomized rats induce uterine sensitivity to 5-HT in vitro. The administration of 3 beta NET in vivo, which is the NET metabolite with the highest affinity for the estrogen receptor, induced a maximal contractile response to serotonin similar to that of 17 beta-estradiol treatment. The other metabolites induced less uterine activity. According to the effective dose 50, the order of estrogenic potency was 17 beta-estradiol > 3 beta 5 alpha NET > 3 alpha 5 alpha NET > NET > 5 alpha NET. The estrogenic effect of 3 beta 5 alpha- and 3 alpha 5 alpha NET may be exerted through their interaction with the estrogen receptor, whereas NET and 5 alpha NET, which do not bind to the estrogen receptor and display a minor estrogenic activity, require prior bioconversion to 3 beta 5 alpha NET and perhaps to 3 alpha 5 alpha NET. The A-ring reduced metabolites of NET, mainly the 3 beta 5 alpha NET, may be exerting estrogenic responses and modulating uterine activity when administered in vivo.
炔诺酮（NET）的雌激素样作用似乎是由3β5α - 和3α5α - 四氢炔诺酮（分别为3β5α - 和3α5α - NET）与雌激素受体的相互作用介导的。鉴于体外子宫对血清素（5 - HT）的收缩反应特别依赖于雌激素，本研究的目的是调查给去卵巢大鼠体内注射NET及其A环还原代谢产物是否会诱导子宫在体外对5 - HT敏感。体内注射对雌激素受体亲和力最高的NET代谢产物3βNET，可诱导出与17β - 雌二醇治疗相似的对血清素的最大收缩反应。其他代谢产物诱导的子宫活性较低。根据半数有效剂量，雌激素活性顺序为17β - 雌二醇> 3β5αNET> 3α5αNET> NET> 5αNET。3β5α - 和3α5αNET的雌激素作用可能是通过它们与雌激素受体的相互作用来发挥的，而不与雌激素受体结合且显示出较小雌激素活性的NET和5αNET，需要先生物转化为3β5αNET，可能还需要转化为3α5αNET。NET的A环还原代谢产物，主要是3β5αNET，在体内给药时可能会发挥雌激素反应并调节子宫活性。
