Mora G R, Mahesh V B
Department of Physiology and Endocrinology, Medical college of Georgia, Augusta 30901-3000, USA.
Mol Cell Endocrinol. 1996 Nov 29;124(1-2):111-20. doi: 10.1016/s0303-7207(96)03939-1.
Recent work from our laboratory has focused on elucidating the mechanism of androgen regulation of the androgen receptor (AR). We have demonstrated that testosterone increases AR protein and binding within 1 h in the ventral prostate of adult rats castrated for 24 h. Cycloheximide administered with testosterone reduces AR and AR mRNA levels. AP-1/c-fos transcription factor has been shown to function as a negative in many systems. c-fos mRNA levels were decreased 1 h after testosterone treatment in the ventral prostate, whereas they were increased in cycloheximide alone or cycloheximide-testosterone treated groups as compared to vehicle control. c-fos protein was also increased in the testosterone-cycloheximide treated group as compared to testosterone alone or cycloheximide alone groups at 1 h. By 3 h, the tissue recovers from the inhibitory effect of cycloheximide as evidenced by restoration of AR and an increase in AR mRNA levels. At this time c-fos protein levels were reduced after treatment with cycloheximide and testosterone and c-fos mRNA levels were comparable to the controls. These results suggest that elevation of c-fos expression is associated with a decrease in AR and mRNA and provide correlative data supporting negative repression by c-fos on androgen receptors levels. Between the age of 25-85 days, serum testosterone levels reached adult levels by the age of 55 days. Steady-state AR mRNA levels increased significantly by the age of 85 days while c-fos mRNA levels remained at low baseline levels at all ages. Thus, in addition to the circulating levels of serum testosterone, other age related factors are also involved in the regulation of AR mRNA levels. Furthermore, androgens appear to maintain androgen receptor levels and androgen sensitivity by continuous suppression of the repressor, c-fos.
我们实验室最近的工作集中在阐明雄激素对雄激素受体（AR）的调节机制。我们已经证明，在成年大鼠去势24小时后的腹侧前列腺中，睾酮在1小时内可增加AR蛋白及结合力。与睾酮同时给予的放线菌酮可降低AR及AR mRNA水平。在许多系统中，AP-1/c-fos转录因子已被证明起负性作用。睾酮处理腹侧前列腺1小时后，c-fos mRNA水平下降，而与溶媒对照相比，单独使用放线菌酮或放线菌酮-睾酮处理组中c-fos mRNA水平升高。与单独使用睾酮或单独使用放线菌酮组相比，在1小时时，睾酮-放线菌酮处理组的c-fos蛋白也增加。到3小时时，组织从放线菌酮的抑制作用中恢复，这表现为AR的恢复及AR mRNA水平的增加。此时，放线菌酮和睾酮处理后c-fos蛋白水平降低，c-fos mRNA水平与对照组相当。这些结果表明，c-fos表达的升高与AR及mRNA的减少相关，并提供了相关数据支持c-fos对雄激素受体水平的负性抑制作用。在25至85日龄之间，血清睾酮水平在55日龄时达到成年水平。到85日龄时，AR mRNA的稳态水平显著增加，而c-fos mRNA水平在所有年龄段均维持在低基线水平。因此，除了血清睾酮的循环水平外，其他与年龄相关的因素也参与AR mRNA水平的调节。此外，雄激素似乎通过持续抑制阻遏物c-fos来维持雄激素受体水平及雄激素敏感性。
