TRANSFORMING GROWTH-FACTOR-BETA (BETA-1, BETA-2, AND BETA-3) GENE-EXPRESSION AND ACTION DURING PUBERTAL DEVELOPMENT OF THE SEMINIFEROUS TUBULE - POTENTIAL ROLE AT THE ONSET OF SPERMATOGENESIS

The potential role of transforming growth factor-beta (TGFbeta) as a mediator of cell-cell interactions during the pubertal development of the seminiferous tubule was examined. Mesenchymal-derived peritubular cells and epithelial-like Sertoli cells were isolate from prepubertal, midpubertal, and late pubertal rat testes. The developmental expression of the multiple forms of TGFbeta (TGFbeta1, -beta2, and -beta3) in whole testis and isolated somatic cell types was determined using a nuclease protection analysis. TGFbeta1 and TGFbeta2 mRNA expression was predominant in the immature testis and decreased at the onset of puberty. TGDbeta3 mRNA expression, the most abundant form of TGFbeta present, peaked at an early pubertal stage, coincident with the initiation of spermatogenesis. Peritubular and Sertoli cells expressed each isoform of TGFbeta during development. Peritubular cell mRNA expression of TGFbeta1, -beta2, and -beta3 decreased during pubertal development upon differentiation of this cell type. Sertoli cell expression of TGFbeta1 increased slightly and plateaued during pubertal development. TGFbeta2 mRNA expression was evident only in immature prepubertal Sertoli cells. Sertoli cell mRNA expression of TGFbeta3 increased transiently at the onset of puberty, corresponding with the peak of expression observed during the analysis of whole testicular development. Immunoblot analysis indicated that both cultured peritubular and Sertoli cells can produce the proteins for TGFbeta1, -beta2, and -beta3. Analysis of the hormonal regulation of TGFbeta expression revealed that FSH caused a dramatic decrease in Sertoli cell TGFbeta2 expression while having no effect on TGFbeta1 or TGFbeta3 expression. Potential actions of TGFbeta in the seminiferous tubule were also examined. TGFbeta1 inhibited TGFalpha-induced [H-3]thymidine incorporation into peritubular cell DNA with cells from each developmental stage examined. TGFbeta1 had no effect on Sertoli cell proliferation. Previously, germinal cells have been shown to be responsive to TGFbeta. This study demonstrates the potential of having a unique hormone-dependent pattern of TGFbeta isoform expression during postnatal organ development. Observations demonstrate that the suppression of TGFbeta2 expression, in part in response to FSH, and the transient increase in TGFbeta3 expression correlate with the onset of puberty and the induction of spermatogenesis.