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Orchiectomy markedly reduces the concentration of the three isoforms of transforming growth factor beta in rat bone,
R K Gill1, R T Turner, T J Wronski
1Department of Medicine, Medical University of South Carolina and Department of Veterans Affairs Medical Center, Charleston 29401-5799, USA.
Abstract:
Available evidence indicates that transforming growth factor beta (TGFbeta) is produced by bone cells, that production is enhanced by testosterone and dihydrotestosterone, and that TGFbeta is an important modulator of bone formation, induction, and repair. To determine the relative concentrations of isoforms of skeletal TGFbeta, whether orchiectomy alters the concentration of TGFbeta 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 (n = 20) or 100 mg testosterone (n = 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. TGFbeta1 in skeletal extracts was much more abundant than TGFbeta2 or TGFbeta3. Orchiectomy reduced skeletal TGFbeta by over 80 percent, and reduction was prevented by testosterone replacement. The relative abundance of the three isoforms of TGFbeta in bone was not influenced by orchiectomy or testosterone replacement, and skeletal messenger RNA of TGFbeta1 and TGFbeta2 was not altered 4 weeks after orchiectomy. Messenger RNA for TGFbeta3 was below the limits of detection. Thus, testosterone deficiency markedly diminishes skeletal TGFbeta, and reduction is prevented by testosterone replacement. The findings support the hypothesis that testosterone and TGFbeta are required for maintenance of the skeleton in male rats.
Insights
Testosterone deficiency significantly reduces skeletal transforming growth factor beta (TGFbeta) in male rats. Testosterone replacement therapy prevents this reduction, highlighting testosterone
Area of Science:
- Endocrinology
- Bone Biology
- Reproductive Biology
Background:
- Transforming growth factor beta (TGFbeta) is a key modulator of bone formation, induction, and repair.
- Bone cells produce TGFbeta, with production enhanced by androgens like testosterone.
- The role of testosterone in regulating skeletal TGFbeta levels requires further elucidation.
Purpose of the Study:
- To quantify skeletal TGFbeta isoforms in male rats.
- To investigate the impact of orchiectomy on skeletal TGFbeta concentrations.
- To determine if testosterone replacement prevents orchiectomy-induced alterations in skeletal TGFbeta.
Main Methods:
- Male Sprague-Dawley rats underwent sham-operation or orchiectomy, with or without testosterone replacement.
- Skeletal tissues were analyzed for TGFbeta isoforms and messenger RNA (mRNA) levels.
- Serum calcium, phosphorus, and testosterone levels were measured.
Main Results:
- Orchiectomy significantly reduced skeletal TGFbeta levels by over 80%, an effect prevented by testosterone replacement.
- TGFbeta1 was the most abundant isoform; relative isoform abundance and TGFbeta1/2 mRNA levels were not affected by orchiectomy or testosterone.
- Orchiectomy lowered serum testosterone and phosphorus, which was normalized by testosterone replacement.
Conclusions:
- Testosterone deficiency markedly diminishes skeletal TGFbeta levels in male rats.
- Testosterone replacement therapy effectively prevents the reduction of skeletal TGFbeta.
- These findings support the hypothesis that testosterone and TGFbeta are crucial for maintaining skeletal integrity in males.