LOCALIZATION OF TRANSFORMING GROWTH-FACTOR BETA-1 AND BETA-2 DURING TESTICULAR DEVELOPMENT IN THE RAT

The transforming growth factor betas (TGFbetas) affect the metabolic activities of the somatic cells of the testis. Sertoli cells, peritubular/myoid cells, and germ cells contain mRNA for TGFbeta1 and/or TGFbeta2. We have used immunohistochemical techniques to determine, in vivo, when TGFbeta1 and TGFbeta2 are present in the rat testis during development and have identified the precise localization of these growth factors. The most pronounced changes in TGFbeta immunoreactivity occurred during spermatogenesis. TGFbeta1 predominated in spermatocytes and early round spermatids, but as the spermatids elongated around stages VIII-IX of the cycle, the TGFbeta1 levels declined. TGFbeta2 was undetectable in spermatocytes and early round spermatids, but as spermiogenesis progressed, around stages V-VI, the spermatids rapidly acquired TGFbeta2. The intense staining for TGFbeta2 was maintained as the spermatids elongated. TGFbeta1 immunoreactivity was detected in Sertoli cells throughout testicular development. TGFbeta2 was found in fetal Sertoli cells, but became undetectable rapidly after birth. In fetal animals the Leydig cells contained TGFbeta1 and TGFbeta2; after birth TGFbeta1 persisted whereas TGFbeta2 became undetectable in the Leydig cells. Prior to puberty, TGFbeta1 and TGFbeta2 were absent in a portion of the Leydig cells; when the adult stage was reached, TGFbeta1 was no longer detectable and TGFbeta2 staining was faint to absent. In conclusion, our novel findings show that TGFbeta1 and TGFbeta2 are present in vivo in testicular cells at clearly defined stages of their differentiation. From the changes in the pattern of localization of these peptides, we conclude that they are strictly regulated in the somatic cells and the germ cells. An important outcome of the precise localization studies in vivo is that they have pointed to the stages of spermatogenesis at which TGFbeta is likely to play a physiological role in growth and/or differentiation.