Differential regulation of steady state 4-ene steroid 5 alpha-reductase messenger ribonucleic acid levels along the rat epididymis.

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.