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The mRNAs for the steroid 5 alpha-reductase isozymes, types 1 and 2, are differentially regulated in the rat epididymis.

The enzyme steroid 5 alpha-reductase (EC 1.3.1.22) catalyzes the conversion of testosterone to its more potent form, dihydrotestosterone (DHT), 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 regulators of epididymal structure and function. Two rat 5 alpha-reductase transcripts, designated types 1 and 2, have been identified. Our laboratory has previously characterized the endocrine and developmental regulation of the 5 alpha-reductase type 1 mRNA in the rat epididymis. However, regulation of the type 2 mRNA has not been investigated. Thus, we undertook to characterize the longitudinal distribution of the steady state 5 alpha-reductase type 2 mRNA as well as the effects of development and of unilateral efferent duct ligation on its expression in the rat epididymis. To contrast the regulation of the type 2 5 alpha-reductase isozyme mRNAs in the rat epididymis, these data have been compared with those previously obtained for the type 1 mRNA and enzyme activity. An analysis of the longitudinal distribution of the type 2 transcript along the epididymis revealed that its mRNA was expressed predominantly in the proximal caput region of the tissue. This regional distribution pattern differed markedly from the patterns previously described for the type 1 mRNA and enzyme activity. Surprisingly, a segment-by-segment analysis showed that epididymal 5 alpha-reductase type 2 mRNA 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 1 mRNA and enzyme activity that have been reported to occur during puberty in the rat. In the final experiment, the effect of unilateral efferent duct ligation revealed that 5 alpha-reductase type 2 mRNA levels increased in the initial segment of the ligated 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. Moreover, this is the first report of a tissue in which the mRNAs for the steroid 5 alpha-reductase isozymes are regulated differently.