Orchiectomy markedly reduces the concentration of the three isoforms of transforming growth factor β in rat bone, and reduction is prevented by testosterone

Available evidence indicates that transforming growth factor beta (TGF beta) is produced by bone cells, that production is enhanced by testosterone and dihydrotestosterone, and that TGF beta is an important modulator of bone formation, induction, and repair. To determine the relative concentrations of isoforms of skeletal TGF beta, whether orchiectomy alters the concentration of TGF beta in long bones, and whether alteration is prevented by testosterone replacement, male Sprague-Dawley rats were either sham-operated and given placebo (n = 20) or orchiectomized and given either placebo tn = 20) or 100 mg testosterone in = 20) by slow-release pellets implanted sc at the back of the neck and killed at 6 weeks. Orchiectomy did not change serum calcium and lowered serum testosterone and serum phosphorus; these reductions were prevented by testosterone replacement. TGF beta(1) in skeletal extracts was much more abundant than TGF beta(2) or TGF beta(3). Orchiectomy reduced skeletal TGF beta by over 80 percent, and reduction was prevented by testosterone replacement. The relative abundance of the three isoforms of TGF beta in bone was not influenced by orchiectomy or testosterone replacement, and skeletal messenger RNA of TGF beta, and TGF beta(2) was not altered 4 weeks after orchiectomy. Messenger RNA for TGF beta(3) was below the limits of detection. Thus, testosterone deficiency markedly diminishes skeletal TGF beta, and reduction is prevented by testosterone replacement. The findings support the hypothesis that testosterone and TGF beta are required for maintenance of the skeleton in male rats.