（3H）7α，17α-二甲基-19-去甲睾酮（米勃酮）与孕酮受体的结合：与（3H）R5020和（3H）ORG2058结合的比较。

Binding of (3H)7 alpha,17 alpha-dimethyl-19-nortestosterone (mibolerone) to progesterone receptors: comparison with binding of (3H)R5020 and (3H)ORG2058.

作者信息

Traish A M, Williams D F, Wotiz H H

出版信息

Steroids. 1986 Feb-Mar;47(2-3):157-73. doi: 10.1016/0039-128x(86)90086-3.

Abstract

The binding characteristics of (3H)7 alpha,17 alpha-dimethyl-19-nortestosterone [3H)DMNT) to progesterone receptors (PgR) of calf uterine tissue cytosol were determined and compared to those of the synthetic progestins (3H)ORG2058 and (3H)R5020. Scatchard plot analysis of the equilibrium binding data showed that (3H)DMNT binds to calf uterine PgR with a KD of 2.35 +/- 1.1 nM. This value is slightly higher than that of (3H)R5020 (KD = 1.16 +/- 0.4 nM) and (3H)ORG2058 (KD = 1.04 +/- 0.65 nM). Analysis of dissociation kinetics showed that (3H)DMNT dissociates much more rapidly from the receptor than the other two ligands. Competition experiments showed that ORG2058 has a lower inhibition constant (Ki) than DMNT. Sucrose density gradient (SDG) analysis of PgR showed that (3H)ORG2058-PgR complexes sediment as 8S, (3H)R5020-PgR complexes sediment as 8S and 4S, and (3H)DMNT-PgR complexes sediment as 8S entities along with dissociated (3H)steroid. These data suggest that (3H)DMNT binds to PgR with lower affinity than (3H)ORG2058 and (3H)R5020. The number of binding sites detected with (3H)DMNT are significantly lower than those measured with (3H)ORG2058.

摘要

测定了（3H）7α，17α-二甲基-19-去甲睾酮[（3H）DMNT]与小牛子宫组织胞质溶胶中孕酮受体（PgR）的结合特性，并与合成孕激素（3H）ORG2058和（3H）R5020的结合特性进行了比较。对平衡结合数据的Scatchard图分析表明，（3H）DMNT与小牛子宫PgR结合的解离常数（KD）为2.35±1.1 nM。该值略高于（3H）R5020（KD = 1.16±0.4 nM）和（3H）ORG2058（KD = 1.04±0.65 nM）。解离动力学分析表明，（3H）DMNT从受体上解离的速度比其他两种配体快得多。竞争实验表明，ORG2058的抑制常数（Ki）低于DMNT。对PgR的蔗糖密度梯度（SDG）分析表明，（3H）ORG2058-PgR复合物以8S沉降，（3H）R5020-PgR复合物以8S和4S沉降，（3H）DMNT-PgR复合物以8S形式沉降，同时伴有解离的（3H）类固醇。这些数据表明，（3H）DMNT与PgR结合的亲和力低于（3H）ORG2058和（3H）R5020。用（3H）DMNT检测到的结合位点数明显低于用（3H）ORG2058测得的结合位点数。