GENE-EXPRESSION IN THE AGING BROWN-NORWAY RAT EPIDIDYMIS

The mammalian epididymis is the site where spermatozoa are matured and then stored. Though many studies have described epididymal functions and their regulation, little is known about how aging affects this tis sue. The Brown Norway rat, which does not show the many age-related pa thologies common to other rat strains, was used as a model to study ag ing of the epididymis. The present study was designed to determine the effect of aging on the mRNA levels for selected markers of epididymal function. Brown Norway rats ranging in age from 6 to 30 months were e xamined at 6-month intervals; epididymides were sectioned into caput-c orpus and cauda regions, Relative mRNA concentrations were assessed us ing Northern blot analysis and specific cDNAs for the rat 5 alpha-redu ctase isozymes, types 1 and 2; proenkephalin; the androgen receptor; e pididymal proteins B/C and D/E; and sulfated glycoprotein-2 (SGP-2, cl usterin). Northern blots were quantitated by densitometric scanning. I n the caput-corpus epididymidis, 5 alpha-reductase type 1 and type 2 m RNA levels decreased significantly by 43% and 33%, respectively, betwe en 6 and 12 months and by 64% and 40%, respectively, between 6 and 30 months. No significant change, however, was found in the expression of the 5 alpha-reductase mRNAs in the cauda epididymidis. interestingly, proenkephalin mRNA was only detected in the caput-corpus epididymidis of 6-month-old rats. In marked contrast to the 5 alpha-reductase isoz ymes and proenkephalin, no significant age-related changes were observ ed in the mRNA levels for the androgen receptor, protein B/C, or prote in D/E. No age-related changes in mRNA expression for SGP-2 occurred i n the caput-corpus epididymidis. However, in the cauda epididymidis, S GP-2 mRNA levels rose by twofold between 6 and 18 months and then decr eased sharply by 75% between 18 and 30 months. We conclude that as the epididymis ages, the expression of genes for certain specific markers of epididymal function is affected in a region-specific manner. Furth er, the decrease in the concentrations of the mRNAs for the 5 alpha-re ductase isozymes and proenkephalin in the epididymis between 6 and 12 months is thus far the earliest marker for aging in the male reproduct ive tract of the Brown Norway rat.