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 (TGF beta) 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 isolated from prepubertal, midpubertal, and late pubertal rat testes. The developmental expression of the multiple forms of TGF beta (TGF beta 1, -beta 2, and -beta 3) in whole testis and isolated somatic cell types was determined using a nuclease protection analysis. TGF beta 1 and TGF beta 2 mRNA expression was predominant in the immature testis and decreased at the onset of puberty. TGF beta 3 mRNA expression, the most abundant form of TGF beta present, peaked at an early pubertal stage, coincident with the initiation of spermatogenesis. Peritubular and Sertoli cells expressed each isoform of TGF beta during development. Peritubular cell mRNA expression of TGF beta 1, -beta 2, and -beta 3 decreased during pubertal development upon differentiation of this cell type. Sertoli cell expression of TGF beta 1 increased slightly and plateaued during pubertal development. TGF beta 2 mRNA expression was evident only in immature prepubertal Sertoli cells. Sertoli cell mRNA expression of TGF beta 3 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 TGF beta 1, -beta 2, and -beta 3. Analysis of the hormonal regulation of TGF beta expression revealed that FSH caused a dramatic decrease in Sertoli cell TGF beta 2 expression while having no effect on TGF beta 1 or TGF beta 3 expression. Potential actions of TGF beta in the seminiferous tubule were also examined. TGF beta 1 inhibited TGF alpha-induced [3H]thymidine incorporation into peritubular cell DNA with cells from each developmental stage examined. TGF beta 1 had no effect on Sertoli cell proliferation. Previously, germinal cells have been shown to be responsive to TGF beta. This study demonstrates the potential of having a unique hormone-dependent pattern of TGF beta isoform expression during postnatal organ development. Observations demonstrate that the suppression of TGF beta 2 expression, in part in response to FSH, and the transient increase in TGF beta 3 expression correlate with the onset of puberty and the induction of spermatogenesis.