LOCALIZATION OF CLASS-I AND CLASS-IV ALCOHOL DEHYDROGENASES IN MOUSE TESTIS AND EPIDIDYMIS - POTENTIAL RETINOL DEHYDROGENASES FOR ENDOGENOUS RETINOIC ACID SYNTHESIS

The vitamin A metabolite retinoic acid plays an essential signaling ro le in spermatogenesis by acting as a ligand for nuclear retinoic acid receptors. However, little is known about the regulation of retinoic a cid synthesis from vitamin A (retinol). Here we have examined mouse te stis and epididymis for the presence of endogenous retinoic acid and f or the expression of genes encoding class I and class IV alcohol dehyd rogenases (ADH), both of which catalyze retinol oxidation, the rate-li miting step in the conversion of retinol to retinoic acid. Using a bio assay we found that mouse testis and epididymis both have significant levels of retinoic acid ranging from 7 to 8 pmol/g, an amount known to be sufficient to optimally activate retinoic acid receptors. In situ hybridization analysis of mouse testis revealed that class I ADH mRNA was localized in Sertoli cells and Leydig cells, while class IV ADH mR NA was confined to late spermatids. In the epididymis, class I ADH mRN A was detected in both principal and basal cells, whereas class IV ADH mRNA was limited to basal cells. Immunohistochemical analyses of test is indicated that class I ADH protein was localized in Sertoli and Ley dig cells, whereas class IV ADH protein was observed only in late sper matids. Class I ADH protein was localized in principal and basal cells of the cauda epididymidis but only in basal cells of the caput epidid ymidis. Class IV ADH protein was limited to basal cells along the enti re length of the epididymis. These results support a role for ADHs dur ing spermatogenesis, potentially as retinol dehydrogenases catalyzing local retinoic acid synthesis in the testis and epididymis.