Deslypere J P, Young M, Wilson J D, McPhaul M J
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8857.
Mol Cell Endocrinol. 1992 Oct;88(1-3):15-22. doi: 10.1016/0303-7207(92)90004-p.
Testosterone and its 5 alpha-reduced derivative 5 alpha-dihydrotestosterone exert different actions in the male during embryogenesis and in postnatal life. Nevertheless the two hormones bind to the same intracellular androgen receptor, and genetic and endocrinological studies in the Tfm mouse suggest that the actions of both hormones are mediated by this single receptor. Previous studies indicate that dihydrotestosterone binds more tightly to the androgen receptor but that the Bmax of binding of the two hormones is the same. To determine whether these differences in binding parameters could explain the mechanism by which the two hormones exert different physiological actions via the same receptor, we introduced a plasmid encoding the androgen receptor cDNA and a reporter plasmid encoding MMTV-CAT into Chinese hamster ovary cells. These cells do not express endogenous androgen receptor and do not convert testosterone to dihydrotestosterone. Therefore, it was possible to examine the relation between the concentration of each of the steroids and reporter gene expression. Both hormones enhanced CAT activity, but dihydrotestosterone was approximately 10 times as potent (half maximal of 0.018 nM) as testosterone (half maximal of 0.2 nM); the maximal activity achieved was the same for the two androgens. These findings are nearly identical to the apparent Kd values for the interaction of the two hormones with the androgen receptor. Although testosterone and dihydrotestosterone may influence the expression of other genes differently, these findings are compatible with a model system in which the differential effects can be explained as a consequence of different binding affinities to the receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
睾酮及其5α-还原衍生物5α-双氢睾酮在雄性胚胎发育及出生后的生命过程中发挥着不同的作用。然而，这两种激素都与同一细胞内雄激素受体结合，对Tfm小鼠的遗传学和内分泌学研究表明，这两种激素的作用均由这单一受体介导。先前的研究表明，双氢睾酮与雄激素受体的结合更紧密，但两种激素结合的Bmax相同。为了确定结合参数的这些差异是否能够解释这两种激素通过同一受体发挥不同生理作用的机制，我们将编码雄激素受体cDNA的质粒和编码MMTV-CAT的报告质粒导入中国仓鼠卵巢细胞。这些细胞不表达内源性雄激素受体，也不会将睾酮转化为双氢睾酮。因此，有可能研究每种类固醇的浓度与报告基因表达之间的关系。两种激素均增强了CAT活性，但双氢睾酮的效力约为睾酮的10倍（半数有效浓度分别为0.018 nM和0.2 nM）；两种雄激素达到的最大活性相同。这些发现与两种激素与雄激素受体相互作用的表观Kd值几乎相同。尽管睾酮和双氢睾酮可能对其他基因的表达有不同影响，但这些发现与一个模型系统相符，在该系统中，差异效应可解释为对受体不同结合亲和力的结果。（摘要截取自250词）
