Age-related changes in human oestrogen receptor α function and levels in osteoblasts
Age-related changes in human oestrogen receptor α function and levels in osteoblasts
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DOI：
10.1042/bj3330787
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发表时间：
1998-08-01
影响因子：
4.1
通讯作者：
Fedarko, NS
中科院分区：
文献类型：
--
作者：
Ankrom, MA;Patterson, JA;Fedarko, NS
雌激素受体（ER）存在于人成骨细胞中，并介导对骨的抗吸收作用。在明确定义的条件下，在体外利用来自未进行激素替代疗法的不同年龄健康女性供体的人成骨细胞样细胞来研究ER功能和水平。用来自8名年轻女性（小于50岁）的0.1 nM雌二醇-17 β细胞株处理显著增加羟脯氨酸水平[平均（2.2 +/-0.1 S.E.M.）-（1.5 ± 0.1 S.E.M.）倍数增加]，而来自9名老年妇女（50岁以上）的细胞没有受到显著影响。类似地，来自年轻女性的细胞株，用与氯霉素乙酰转移酶连接的共有雌激素应答元件转染，比来自老年女性的细胞株对雌激素表现出更大的应答。当通过酶免疫测定法测量基础ER α水平并在每个细胞的基础上标准化时，来自年轻女性的成骨细胞样株（n = 24）每10（6）个细胞具有2.54 +/-0.16fmol的ER α平均值。相比之下，来自老年妇女的菌株（n = 20）每10（6）个细胞中ER α的平均值为5.44 +/- 0.48 fmol。在人类皮肤来源的成纤维细胞中也观察到ER α数量的年龄相关性增加，并直接在未接受激素替代治疗的女性的真皮活检中观察到。结果表明配体浓度依赖性ER α诱导，并表明随着供体年龄的增加，受体调节的丧失和配体-受体信号转导的减少。
Oestrogen receptors (ERs) are present in human osteoblasts and mediate anti-resorptive effects on bone. Human osteoblast-like cells derived from different aged healthy female donors not on hormone replacement therapy were utilized under well-defined conditions in vitro to investigate ER function and levels, Treatment with 0.1 nM oestradiol-17 beta of cell strains derived from eight young women (less than 50 years of age) increased hydroxyproline levels significantly [an average (2.2 +/- 0.1 S.E.M.)-fold increase], whereas cells derived from nine older women (more than 50 years of age) were not significantly affected. Similarly, cell strains, derived from younger women, transfected with a consensus oestrogen-responsive element linked to chloramphenicol acetyltransferase exhibited a greater response to oestrogen than strains derived from older women, When basal ER alpha levels were measured by enzyme immunoassay and normalized on a per cell basis, osteoblast-like strains derived from younger women (n = 24) had a mean value of 2.54 +/- 0.16 fmol of ER alpha per 10(6) cells. In contrast, strains derived from older women (n = 20) had a mean value of 5.44 +/- 0.48 fmol of ER alpha per 10(6) cells. An age-related increase in ER alpha number was also observed in human skin-derived fibroblasts and directly in dermal biopsies from women not on hormone replacement therapy. The results demonstrate ligand concentration-dependent ER alpha induction and indicate a loss of receptor regulation and diminution of ligand-receptor signal transduction with increasing donor age.