The localization of androgen receptors in human bone

The localization of androgen receptors in human bone
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DOI:
10.1210/jc.82.10.3493
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发表时间:
1997-10-01
影响因子:
5.8
通讯作者:
Compston, JE
Compston, JE
中科院分区:
医学2区
文献类型:
--
作者:
Abu, EO;Horner, A;Compston, JE

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雄激素对人类骨骼有重要影响,无论是男性还是女性,雄激素缺乏都与骨质流失有关。雄激素的骨骼作用可直接通过雄激素受体(AR)介导,也可通过雌激素受体芳构化为雌激素后间接介导。雄激素受体在体外已被证实存在于骨细胞和软骨细胞中,但在人骨组织中的存在尚未见报道。为了进一步证明雄激素通过雄激素受体对骨的直接作用,我们用特异性的单抗研究了人AR在正常发育骨和骨赘生骨中的表达。在发育骨的生长板中,雄激素受体主要表达在肥大的软骨细胞和成骨细胞中。在骨骼中的骨细胞,以及骨髓中的单核细胞和血管内皮细胞中也观察到了它们。在骨赘中,雄激素受体广泛分布于增殖、成熟和肥大的软骨细胞的软骨内成骨部位和成骨细胞的骨重建部位。它们也在骨髓内的骨细胞和单核细胞中表达。本研究首次发现雄激素受体在正常发育的人和骨赘生骨中的存在和分布,为雄激素对骨和软骨细胞的直接作用提供了证据。
Androgens have important effects on the human skeleton, and deficiency has been associated with bone loss in both males and females. The skeletal actions of androgens may be mediated directly via the androgen receptor (AR) or indirectly via the estrogen receptor after aromatization to estrogens. The presence of androgen receptors has been demonstrated in bone cells and chondrocytes in vitro, but their presence in human bone in situ has not been reported. In order to provide further evidence for a direct action of androgens on bone via androgen receptors, we have used specific monoclonal antibodies to investigate the expression of human AR in normal developing and osteophytic bone of both sexes.In the growth plates from the developing bone, androgen receptors were predominantly expressed in hypertrophic chondrocytes and in osteoblasts at sites of bone formation. They were also observed in osteocytes in the bone, and in mononuclear cells and endothelial cells of blood vessels within the bone marrow. In the osteophytes, androgen receptors were widely distributed at sites of endochondral ossification in proliferating, mature, and hypertrophic chondrocytes and at sites of bone remodeling in osteoblasts. They were also expressed in osteocytes and mononuclear cells within the bone marrow. The pattern and number of cells expressing the receptor was similar in both sexes.Our results show for the first time the presence and distribution of androgen receptors in normal developing human and osteophytic bone in, situ and further provide evidence for a direct action of androgens on bone and cartilage cells.