Viger R S, Robaire B
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Endocrinology. 1991 May;128(5):2407-14. doi: 10.1210/endo-128-5-2407.
Epididymal nuclear 5 alpha-reductase enzyme activity is regulated by a testosterone-dependent factor from the testis. Regulation at the mRNA level, however, has not been investigated. Endocrine manipulation experiments were designed to determine whether 5 alpha-reductase is regulated at the steady state mRNA level. Steady state mRNA concentrations were assessed using the full-length cDNA for female rat liver 5 alpha-reductase. Longitudinal distribution showed that the highest mRNA concentrations were present in the initial segment of the caput epididymidis and were 3- to 7-fold higher than in the other tissue segments. The androgen dependence of the mRNA levels for 5 alpha-reductase was assessed by bilateral orchidectomy and simultaneous testosterone replacement therapy. One week after surgery, mRNA concentrations in orchidectomized rats were decreased to 15% of control levels in the initial segment of the caput epididymidis and to 40-50% of control levels in the remaining epididymal segments. Administration of testosterone at a dose that mimics normal serum concentrations (2.5-cm Silastic implant) restored 5 alpha-reductase mRNA concentrations to control levels in the corpus and cauda epididymidis, but these were not significantly different from orchidectomized levels (P greater than or equal to 0.05) in the initial segment and caput epididymidis. Administration of testosterone at a dose designed to approximate 5- to 8-fold normal serum concentrations (18.6-cm implant) maintained 5 alpha-reductase mRNA concentrations at only 50% of control levels in the initial segment, while complete maintenance was observed in the rest of the tissue. The effects of unilateral orchidectomy revealed that 5 alpha-reductase mRNA concentrations decrease selectively in the initial segment of the orchidectomized side. This is the first report that epididymal 5 alpha-reductase is regulated at the mRNA level and that the regulation is different with respect to the segment being studied.
附睾核5α-还原酶的酶活性受来自睾丸的睾酮依赖性因子调控。然而，在mRNA水平的调控尚未得到研究。设计了内分泌操纵实验以确定5α-还原酶在稳态mRNA水平是否受到调控。使用雌性大鼠肝脏5α-还原酶的全长cDNA评估稳态mRNA浓度。纵向分布显示，最高的mRNA浓度存在于附睾头起始段，比其他组织段高3至7倍。通过双侧睾丸切除术和同时进行睾酮替代疗法评估5α-还原酶mRNA水平的雄激素依赖性。手术后一周，去势大鼠附睾头起始段的mRNA浓度降至对照水平的15%，其余附睾段降至对照水平的40 - 50%。以模拟正常血清浓度的剂量（2.5厘米硅橡胶植入物）给予睾酮可使附睾体和尾的5α-还原酶mRNA浓度恢复至对照水平，但在起始段和附睾头与去势水平相比无显著差异（P≥0.05）。以接近正常血清浓度5至8倍的剂量（18.6厘米植入物）给予睾酮，仅使起始段的5α-还原酶mRNA浓度维持在对照水平的50%，而在其余组织中观察到完全恢复。单侧睾丸切除术的结果显示，去势侧起始段的5α-还原酶mRNA浓度选择性降低。这是关于附睾5α-还原酶在mRNA水平受到调控且不同研究段调控方式不同的首次报道。
