Retinoic acid synthesis in the somatic cells of rat seminiferous tubules

At physiological plasma concentrations, retinoic acid (RA) cannot cross the blood-testis barrier formed by Sertoli and peritubular cells, and it is thought to be mainly synthesized in situ through the oxidation of retinol. We have thus examined the in vitro RA biosynthetic capacity of cultured Sertoli and peritubular cells isolated from the seminiferous tubules of prepubertal rats, using hole-cellular retinol binding protein (CRBP) as a substrate. Although both somatic cell types contain CRBP and retinoic acid nuclear receptors, RA synthesis was only detected with Sertoli cell subcellular fractions. Most of the RA synthesizing activity of these cells is contributed by a microsomal-cytosolic system that shares many functional similarities with a RA biosynthetic pathway originally identified in rat liver. RA synthesis is maximal at a time of postnatal life (20 days) preceding meiotic cell accumulation and remains nearly constant thereafter. The unique ability of Sertoli cell subcellular fractions to support RA formation from holoCRBP, along with the observed age-dependent modulation of this activity, indicate that Sertoli cells represent the main site of intratubular RA production and that they may play a key role in controlling RA-dependent processes within the seminiferous tubule.