THE MESSENGER-RNAS FOR THE STEROID 5-ALPHA-REDUCTASE ISOZYMES, TYPE-1AND TYPE-2, ARE DIFFERENTIALLY REGULATED IN THE RAT EPIDIDYMIS

The enzyme steroid 5 alpha-reductase (EC 1.3.1.22) catalyzes the conve rsion of testosterone to its more potent form, dihydrotestosterone (DH T), in many androgen-sensitive target tissues. In the epididymis, the 5 alpha-reduced metabolites of testosterone, DHT and 5 alpha-androstan -3 alpha, 17 beta-diol (3 alpha-diol), are considered the primary regu lators of epididymal structure and function. Two rat 5 alpha-reductase transcripts, designated types 1 and 2, have been identified. Our labo ratory has previously characterized the endocrine and developmental re gulation of the 5 alpha-reductase type 1 mRNA in the rat epididymis. H owever, regulation of the type 2 mRNA has not been investigated. Thus, we undertook to characterize the longitudinal distribution of the ste ady state 5 alpha-reductase type 2 mRNA as well as the effects of deve lopment and of unilateral efferent duct ligation on its expression in the rat epididymis. To contrast the regulation of the type 2 5 alpha-r eductase isozyme mRNAs in the rat epididymis, these data have been com pared with those previously obtained for the type 1 mRNA and enzyme ac tivity. An analysis of the longitudinal distribution of the type 2 tra nscript along the epididymis revealed that its mRNA was expressed pred ominantly in the proximal caput region of the tissue. This regional di stribution pattern differed markedly from the patterns previously desc ribed for the type 1 mRNA and enzyme activity. Surprisingly, a segment -by-segment analysis showed that epididymal 5 alpha-reductase type 2 m RNA levels were not altered as a function of increasing postnatal age. Again, this result was in marked contrast to the important changes in 5 alpha-reductase type I mRNA and enzyme activity that have been repo rted to occur during puberty in the rat. In the final experiment, the effect of unilateral efferent duct ligation revealed that 5 alpha-redu ctase type 2 mRNA levels increased in the initial segment of the ligat ed side but remained unchanged in the rest of the tissue; this was in marked contrast to the dramatic decrease (>60%) in type 1 mRNA levels observed specifically in the initial segment of the epididymis. Taken together, these experiments demonstrate that 5 alpha-reductase type 1 and type 2 mRNAs are differentially regulated in the rat epididymis. M oreover, this is the first report of a tissue in which the mRNAs for t he steroid 5 alpha-reductase isozymes are regulated differently.