Kurowski T T, Capaccio J A, Chatterton R T, Hickson R C
Proc Soc Exp Biol Med. 1985 Feb;178(2):215-21. doi: 10.3181/00379727-178-42001.
The present study was undertaken to determine cytosol binding properties of [3H]methyltrienolone, a synthetic androgen, in comparison with [3H]dexamethasone, a synthetic glucocorticoid, under conditions of glucocorticoid excess in skeletal muscle. Male hypophysectomized rats received either seven daily subcutaneous injections of cortisone acetate (CA) (100 mg X kg-1 body wt) or the vehicle, 1% carboxymethyl cellulose. Following treatment, both [3H]dexamethasone and [3H]methyltrienolone-receptor concentrations were decreased from those in vehicle-treated rats by more than 90 and 80%, respectively, in CA-treated animals. Scatchard analysis of [3H]methyltrienolone binding in muscles of vehicle-treated animals became nonlinear at high concentrations of labeled ligand and were reanalyzed by a two-component binding model. The lower affinity, higher capacity component, which was attributed to binding of methyltrienolone to a "dexamethasone" component, disappeared in muscles of CA-treated rats and Scatchard plots were linear. Receptor concentrations of the higher affinity lower capacity "methyltrienolone" component were similar in muscles of vehicle-treated and CA-treated groups. From competition studies, the high relative specificities of glucocorticoids for [3H]methyltrienolone binding in muscles of vehicle-treated animals were markedly reduced by CA treatment. In addition, the binding specificity data also showed strong competition by progesterone and methyltrienolone for [3H]dexamethasone binding and estradiol-17 beta for [3H]methyltrienolone binding. These results demonstrate that most of the [3H]methyltrienolone binding is eliminated under in vivo conditions of glucocorticoid excess. Furthermore, the competitiveness of various steroids for receptor binding suggests that rat muscle may not contain classic (ligand-specific) glucocorticoid and androgen receptors.
本研究旨在比较合成雄激素[3H]甲基三烯醇酮与合成糖皮质激素[3H]地塞米松在骨骼肌糖皮质激素过量情况下的胞质结合特性。雄性去垂体大鼠每日皮下注射醋酸可的松（CA）（100 mg/kg体重）共7天或注射溶媒1%羧甲基纤维素。治疗后，在CA处理的动物中，[3H]地塞米松和[3H]甲基三烯醇酮受体浓度分别比溶媒处理的大鼠降低了90%以上和80%以上。对溶媒处理动物肌肉中[3H]甲基三烯醇酮结合进行Scatchard分析，在高浓度标记配体时呈非线性，随后用双组分结合模型重新分析。低亲和力、高容量组分被认为是甲基三烯醇酮与“地塞米松”组分的结合，在CA处理大鼠的肌肉中消失，Scatchard图呈线性。高亲和力、低容量“甲基三烯醇酮”组分的受体浓度在溶媒处理组和CA处理组的肌肉中相似。从竞争研究来看，CA处理显著降低了糖皮质激素对溶媒处理动物肌肉中[3H]甲基三烯醇酮结合的高相对特异性。此外，结合特异性数据还显示，孕酮和甲基三烯醇酮对[3H]地塞米松结合有强烈竞争，雌二醇-17β对[3H]甲基三烯醇酮结合有强烈竞争。这些结果表明，在糖皮质激素过量的体内条件下，大部分[3H]甲基三烯醇酮结合被消除。此外，各种类固醇对受体结合的竞争性表明，大鼠肌肉可能不含有经典的（配体特异性）糖皮质激素和雄激素受体。
