Ernst M, Heath J K, Schmid C, Froesch R E, Rodan G A
Department of Bone Biology, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
J Steroid Biochem. 1989;34(1-6):279-84. doi: 10.1016/0022-4731(89)90092-7.
Although the beneficial effects of estrogen in the treatment of postmenopausal osteoporosis are well documented, such effects were difficult to demonstrate in in vitro models. However, recent improvements in bone cell culture models (better defined osteoblastic cell populations, omission of Phenol Red from culture media) enabled several investigators to show albeit small, but reproducible, direct effects of estradiol in various osteoblastic cell types. Such findings were supported by the identification of low numbers of high-affinity estrogen receptors in bone cells derived from different mammalian species. The likely physiological relevance of the in vitro results is indicated by the specificity for 17 beta-estradiol, and the requirement for nanomolar concentrations of the hormone, consistent with a Kd of 0.6 nM for estradiol binding to its receptor [56]. In bone in vitro, estradiol may have anticatabolic effects by decreasing parathyroid hormone responsiveness, and anabolic effects by stimulating matrix synthesis and cell proliferation. Insulin-like growth factor-I is likely to be an autocrine/paracrine mediator for the anabolic effects and may, when associated with its binding proteins, effectively act in the bone compartment.
尽管雌激素在治疗绝经后骨质疏松症方面的有益作用已有充分记录，但在体外模型中很难证明这些作用。然而，骨细胞培养模型的最新改进（更好地定义成骨细胞群体、从培养基中去除酚红）使一些研究人员能够证明，尽管雌二醇对各种成骨细胞类型的直接作用很小，但却是可重复的。来自不同哺乳动物物种的骨细胞中存在少量高亲和力雌激素受体，这支持了上述发现。体外实验结果的可能生理相关性体现在对17β-雌二醇的特异性以及对纳摩尔浓度激素的需求上，这与雌二醇与其受体结合的解离常数为0.6 nM一致[56]。在体外骨实验中，雌二醇可能通过降低甲状旁腺激素反应性产生抗分解代谢作用，并通过刺激基质合成和细胞增殖产生合成代谢作用。胰岛素样生长因子-I可能是合成代谢作用的自分泌/旁分泌介质，并且当其与结合蛋白结合时，可能在骨组织中有效发挥作用。
