Orchiectomy markedly reduces the concentration of the three isoforms of transforming growth factor β in rat bone, and reduction is prevented by testosterone
Orchiectomy markedly reduces the concentration of the three isoforms of transforming growth factor β in rat bone, and reduction is prevented by testosterone
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DOI：
10.1210/en.139.2.546
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发表时间：
1998-02-01
期刊：
影响因子：
4.8
通讯作者：
Bell, NH
中科院分区：
文献类型：
--
作者：
Gill, RK;Turner, RT;Bell, NH
现有证据表明，转化生长因子β（TGF β）由骨细胞产生，睾酮和二氢睾酮增强了这种产生，TGF β是骨形成、诱导和修复的重要调节剂。为了确定骨骼TGF β亚型的相对浓度，睾丸切除术是否会改变长骨中TGF β的浓度，以及睾酮替代是否会阻止这种改变，雄性Sprague-Dawley大鼠假手术并给予安慰剂（n = 20）或睾丸切除并给予安慰剂（n = 20）或100 mg睾酮（n = 20），通过缓慢-在颈后皮下植入释放小球并在6周时处死。睾丸切除术没有改变血清钙和降低血清睾酮和血清磷，这些减少被阻止睾酮替代。骨骼提取物中的TGF β（1）比TGF β（2）或TGF β（3）丰富得多。睾丸切除术使骨骼TGF β减少了80%以上，睾丸激素替代治疗可以防止这种减少。骨中TGF β 3种异构体的相对丰度不受睾丸切除术或睾酮替代的影响，并且TGF β和TGF β 2的骨骼信使RNA在睾丸切除术后4周没有改变。TGF β 3的信使RNA低于检测限。因此，睾酮缺乏会显著减少骨骼TGF β，而睾酮替代可以防止减少。这些发现支持了睾酮和TGF β是维持雄性大鼠骨骼所必需的假设。
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.