Reversal of bone loss in mice by nongenotropic signaling of sex steroids
Reversal of bone loss in mice by nongenotropic signaling of sex steroids
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DOI：
10.1126/science.1074935
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发表时间：
2002-10-25
期刊：
影响因子：
56.9
通讯作者：
Manolagas, SC
中科院分区：
文献类型：
--
作者：
Kousteni, S;Chen, JR;Manolagas, SC
我们表明，性类固醇通过一种不同于用于保护生殖器官质量和功能的机制来保护成年小鼠骨骼。性类固醇受体的经典基因性作用对于其骨骼保护作用是可有可无的，但对于其对生殖组织的作用却是必不可少的。一种合成配体（4-雌酯-3 α， 17 - β -二醇），再现性类固醇的非基因致异性效应，而不影响经典转录，在卵巢切除的女性中增加骨量和强度，高于雌激素充满状态的水平，在睾丸切除的男性中至少与双氢睾酮一样有效，而不影响生殖器官。这些配体作为激素替代治疗骨质疏松症的潜在选择值得研究，在女性和男性中都是如此。
We show that sex steroids protect the adult murine skeleton through a mechanism that is distinct from that used to preserve the mass and function of reproductive organs. The classical genotropic actions of sex steroid receptors are dispensable for their bone protective effects, but essential for their effects on reproductive tissues. A synthetic ligand (4-estren-3alpha, 17beta-diol) that reproduces the nongenotropic effects of sex steroids, without affecting classical transcription, increases bone mass and strength in ovariectomized females above the level of the estrogen-replete state and is at least as effective as dihydrotestosterone in orchidectomized males, without affecting reproductive organs. Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis of bone mass in both women and men.