Chávez B A, Vilchis F, Pérez A E, García G A, Grillasca I, Pérez-Palacios G
J Steroid Biochem. 1985 Jan;22(1):121-6. doi: 10.1016/0022-4731(85)90151-7.
The interaction of norethisterone (NET) and four A-ring reduced metabolites of NET with cytosol receptors for progesterone (PR), androgen (AR), and estrogen (ER) was investigated. Cytosol preparations from: uteri of adult estrogen-primed castrated rats, ventral prostates of adult castrated rats and uteri of immature rats were used as the source of PR, AR, and ER respectively. 3H-Labeled ORG-2058, R-1881, and 17 beta-estradiol were used as the radioligands. The results of competitive studies disclosed that: the most efficient competitor for PR binding sites was NET (Ki = 1.1 X 10(-7) M) followed by 5 alpha-dihydro NET (5 alpha-NET), whereas the 3 alpha,5 alpha; 3 beta,5 alpha and 3 alpha,5 beta-tetrahydro NET derivatives were ineffective the most efficient competitor for AR binding sites was 5 alpha-NET (Ki = 1 X 10(-8), immediately followed by NET, while the three tetrahydro NET derivatives were not competitors and remarkable competition for ER binding sites was only exhibited by the 3 beta,5 alpha-tetrahydro NET derivative (Ki = 4.6 X 10(-8) M) and to a lesser extent by its 3 alpha,5 alpha-epimeric alcohol, while NET and 5 alpha-NET were completely ineffective. These findings demonstrate the stereospecificity of the intracellular binding of NET and its reduced metabolites with cytosol steroid putative receptors, and provide biochemical support to the understanding of the variety of hormone-like effects observed after the in vivo administration of NET.
研究了炔诺酮（NET）及其四种A环还原代谢产物与孕酮（PR）、雄激素（AR）和雌激素（ER）胞浆受体的相互作用。分别以成年雌激素预处理去势大鼠的子宫、成年去势大鼠的腹侧前列腺和未成年大鼠的子宫的胞浆制剂作为PR、AR和ER的来源。使用3H标记的ORG - 2058、R - 1881和17β - 雌二醇作为放射性配体。竞争性研究结果表明：PR结合位点最有效的竞争者是NET（Ki = 1.1×10^(-7) M），其次是5α - 二氢NET（5α - NET），而3α,5α；3β,5α和3α,5β - 四氢NET衍生物无效；AR结合位点最有效的竞争者是5α - NET（Ki = 1×10^(-8)），紧随其后的是NET，而三种四氢NET衍生物不是竞争者；仅3β,5α - 四氢NET衍生物（Ki = 4.6×10^(-8) M）对ER结合位点有显著竞争，其3α,5α - 差向异构醇在较小程度上也有竞争，而NET和5α - NET则完全无效。这些发现证明了NET及其还原代谢产物与胞浆类固醇假定受体细胞内结合的立体特异性，并为理解NET体内给药后观察到的多种激素样效应提供了生化支持。
