雌激素调节骨代谢作用的研究进展

雌激素作为一种重要的内源性甾体类激素,具有广泛的生物活性,其可以通过与雌激素受体结合,对生殖系统,中枢神经系统,心血管系统,免疫系统,胰岛功能以及骨代谢等多个方面产生影响。雌激素缺乏是导致绝经后骨质疏松症的主要原因,这一结论已经被多方科研人员证实并得到公认,故雌激素也成为治疗绝经后骨质疏松的主要手段。本文总结了雌激素的来源、雌激素受体的分类和分布、雌激素与骨质疏松的关系、雌激素影响骨代谢的作用机制以及雌激素治疗绝经后骨质疏松症在临床上的应用。其中分别从雌激素通过直接作用和间接作用两方面抑制破骨细胞的重吸收;从减少细胞凋亡、降低氧化应激反应以及减弱NF-k B的活性三种机制总结雌激素增加成骨细胞的形成;从雌激素通过干预骨重建和重吸收过程进而影响骨细胞的整体代谢过程三个大方面入手,将近年来雌激素对骨代谢的作用及机制进行整理归纳,以期为绝经后骨质疏松症的基础实验研究及临床治疗提供更为系统的理论依据。     

选择性雌激素受体调节剂在绝经后骨质疏松症治疗中作用的研究进展

选择性雌激素受体调节剂（SERMs）是一类结构不同的化合物，能与靶器官细胞内的雌激素受体结合而发挥雌激素受体激动剂和拮抗剂的作用。他莫昔芬目前临床上用于进展型乳腺癌的治疗，它还能抑制骨丢失；雷诺昔芬是惟一在世界范围内被用于预防和治疗绝经后骨质疏松症及椎体骨折的药物；尽管如此，SERMs有潜在的副作用。拉索昔芬是一类新的SERM分子，与过去的SERMs相比具有更潜在的效用，目前在Ⅲ期临床研究阶段。     

雌激素受体α基因与骨质疏松症

骨质疏松症病因学复杂,其遗传性状受激素、环境及营养因素调节.已知雌激素在调节骨的内稳态及防止绝经后骨量丢失方面发挥着重要作用.尽管进行了大量相关性研究,但是雌激素受体α基因及其多态性在骨质疏松症病理机制中所起的作用并未取得共识.该文就雌激素受体α基因及其多态性与骨质疏松症关系的研究作一综述.     

雌激素及其受体在骨关节炎中的研究进展

骨关节炎是中老年常见的慢性关节病,在绝经后妇女中发病率最高,提示该疾病应与绝经后雌激素水平的变化密切相关。雌激素及其受体在代谢机制中发挥多种作用,通过多种途径涉及关节软骨和软骨下骨的细胞增殖和凋亡,这成为绝经后女性骨关节炎高发的有力论据。目前,虽然关于雌激素及其受体代谢与骨关节炎相关性的研究并不缺乏,但最新的统一讨论仍然很少。因此,本文从雌激素及其受体影响经典Notch信号通路和胰岛素样生长因子、白细胞介素1 β、基质金属蛋白酶等软细胞代谢调节关节的共同机制,综述了雌激素及其受体与骨关节炎的关系。为今后进一步可能的研究方向提供参考。     

选择性雌激素受体调节剂防治绝经后骨质疏松症

原发性骨质疏松症主要发生于绝经后妇女，与绝经后雌激素降低所致的骨转换加快，骨吸收增加关系密切。目前，防治绝经后骨质疏松症的方法很多，疗效不一。其中针对绝经后低雌激素状态采用的雌激素替代疗法（Ｅｓｔｒｏｇｅｎｒｅ－ｐｌａｃｅｍｅｎｔｔｈｅｒａｐｙ，ＥＲ...     

雌激素及其受体对骨质疏松症影响的研究进展

骨质疏松症(osteoporosis)是一种全身性骨量减少及骨组织微结构改变,从而导致骨脆性增加及易发生骨折的一种常见的、全身性的骨代谢疾病。其致病因素很多,现在认为雌激素水平是影响女性骨密度的重要因素,雌激素缺乏是公认的骨质疏松症的重要诱因之一。雌激素的效应主要通过雌激素受体来发挥。本文就雌激素及其受体对骨质疏松症的影响做一阐述。     

雌激素在骨改建中的调节作用

雌激素在骨改建中的调节作用王震宇戴戎早在本世纪４０年代，Ａｌｂｒｉｇｈｔ提出了绝经后骨质疏松症的概念，认为骨质疏松与卵巢功能衰竭有关。大量研究表明，绝经或切除卵巢后雌激素缺乏导致骨吸收增加，骨量下降；而雌激素替补治疗则抑制骨吸收，减少骨丢失。可见，...     

雌激素受体α基因甲基化与骨质疏松关系的研究进展

妇女绝经后体内雌激素水平显著下降,发生骨质疏松和骨折的风险显著增加。DNA甲基化作为表观遗传作用机制之一,与骨质疏松的发生有着重要关系。雌激素受体α基因甲基化水平升高会抑制雌激素受体α基因的表达,进而影响骨的新陈代谢,但具体作用机制有待于进一步研究。这种甲基化的状态是可以逆转的,通过干预基因甲基化,可以影响骨形成和骨重吸收的过程,进而为诊断和治疗骨质疏松提供新的思路。研究显示血清同型半胱氨酸(Hcy)会影响雌激素受体α基因甲基化水平,绝经后妇女平均血清Hcy浓度显著高于绝经前妇女,提示血清Hcy浓度可以作为早期筛查骨质疏松的指标之一;葛根素达到合适浓度后可抑制成骨细胞雌激素受体α基因甲基化,增强细胞ERαmRNA表达,进而促使成骨细胞增殖分化,从而用于骨质疏松的治疗。通过分析阐明雌激素受体α基因甲基化与骨质疏松的关系,可以早期筛选骨质疏松的高危人群,更简便快捷地诊断骨质疏松,为临床进行基因诊断提供理论依据;可以选择性地开发调节雌激素受体α基因甲基化药物,从而使治疗骨质疏松的靶向性更强,为骨质疏松的基因治疗提供理论依据。     

选择性雌激素受体调节剂与女性压力性尿失禁

雌激素疗法治疗女性尿失禁存在争议。本文综述雌激素与尿失禁的关系,及选择性雌激素受体调节剂(selective estrogen receptor modulators,SERMs)对尿失禁的临床观察及机制研究,为尿失禁的治疗提出新的前景。     

雌激素受体相关受体α与骨代谢

雌激素受体相关受体α(estrogen receptor-related receptorα,ERRα)是最早发现的一种孤儿核受体,是核受体超家族中一员。它与雌激素受体(estrogen receptors,ERs)有着一定的同源性,但尚未发现任何配体。目前研究证明ERRα在骨代谢、能量代谢的调节以及乳腺癌发生中都起到重要作用。本文主要综述ERRα在骨代谢方面的研究进展,特别是在骨组织中对受体介导的雌激素信号途径的参与,以求进一步了解雌激素调控骨改建的机制,以及展望ERRα作为靶点治疗雌激素相关的骨代谢病的前景。     

雌激素受体α及β亚型与绝经后骨质疏松的关系

绝经后雌激素水平下降是绝经后骨质疏松症发病的主要原因,随着年龄增长和绝经后体内雌激素水平降低,骨细胞上的ER的数量和功能均降低,可以部分解释绝经后妇女骨质疏松症发生率骤升的现象,骨细胞上的ER与绝经后骨质疏松症发生有重要的关系。ERα和ERβ在不同部位的骨骼及不同的骨细胞中分布有所差异,二者在骨代谢中可能行使着不同的功能,本文就此进行了详细的综述。     

绝经后骨质疏松症发病机制研究进展

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)是指女性绝经后卵巢内分泌功能失调衰退,导致雌激素水平下降,从而导致破骨细胞的骨吸收大于成骨细胞的骨形成的一种代谢性疾病。骨质疏松症没有特异性的临床表现,直到轻微的创伤诱发骨折时才会引起重视,所以预防骨质疏松症是临床工作的重中之重。目前有很多研究报道了骨质疏松症发生发展的机制,在机体内雌激素的缺乏引起炎症因子与MicroRNA激活,从而引起RANKL-RANK-OPG轴的紊乱,引起骨质流失。同时雌激素充当抗氧化剂来保护骨,抵抗氧化应激。本文就绝经后骨质疏松症的发生机制做一综述。     

Is interaction between age-dependent decline in mechanical stimulation and osteocyte–estrogen receptor levels the culprit for postmenopausal-impaired bone formation?

Declining estrogen levels during menopause are widely considered to be a major cause of age-dependent bone loss, which is primarily manifested by increased bone resorption by osteoclasts. We present accumulating evidence supporting another aspect of metabolic bone loss, suggesting that the combined interaction between age-dependent factors, namely, estrogen deficiency and reduced day-by-day activity/mechanical stimulation, directly leads to a reduction in anabolic processes. Such decreased bone formation results in diminished bone strength and failure to maintain the load-bearing competence of a healthy skeleton and to postmenopausal osteoporosis disorder. Estrogen receptors (ERs), as mediators of estrogenic actions, are essential components of bone osteocyte and osteoblast mechano-adaptive responses. ER expression appears to be upregulated by adequate circulating estrogen levels. ERα signaling pathways participate in the mechanotransduction response through obligatory “non-genomic” actions that occur independently of estrogen binding to ER and by a potentially “genomic”, estrogen-dependent mode. The experimental data indicate that cross talk between the ERα-“non-genomic” and Wnt/β-catenin signaling pathways constitutes the major regulatory mechanism. This interaction uses mechanically and ER-induced prostaglandin E2 as a mediator for the downregulation of osteocyte production of sclerostin. Sclerostin suppression, in turn, is a central prerequisite for load-induced formation and mineralization of the bone matrix. It is therefore plausible that future strategies for preventing and treating postmenopausal osteoporosis may use estrogenic compounds (such as selective estrogen receptor modulators or phytoestrogens) with physical activity, to complement antiresorptive therapy, aimed at stopping further bone loss and possibly even reversing it by stimulation of bone gain.     

镁与女性绝经后骨质疏松的关系研究进展

女性绝经后体内雌激素水平下降可导致骨质疏松。近年来有学者发现,除了雌激素通过调节钙离子水平在骨代谢过程中发挥重要作用外,镁离子也有可能会影响骨质的形成与吸收。血清镁及雌激素相互作用改变了骨质的钙含量,即二者与女性绝经后骨质疏松存在一定关联,但两者之间的具体关系却并不十分明确。众多试验结果表明,相对于单独一种镁离子或钙离子含量对骨质疏松发生率的影响,在女性绝经后体内雌激素水平低下的情况下,镁/钙离子的含量比显得更为重要。研究显示,血清镁离子含量过高或者过低都可能会引起钙离子代谢异常,可能导致两种离子的浓度比失衡,进而对骨代谢产生不利影响,增加女性绝经后患骨质疏松的风险。因此维持绝经后体内镁/钙平衡有利于维持骨组织代谢的稳定,同时为治疗骨质疏松提供线索。即不能单纯的强调补充镁离子或者钙离子,而是应该根据患者血清中钙镁离子的具体浓度和比例来制定治疗方案。     

性激素在老年男性骨质疏松发病及治疗中作用的研究进展

骨质疏松（osteoporosis，OP）与年龄增长密切相关，在老年人群中患病率显著高于中青年人群，严重危害老年人群的健康。性激素在男性骨骼代谢中发挥重要作用，其中，雌激素和雄激素都能够促进骨形成，对抗骨量丢失，而孕激素则可能对男性骨量的维持起到负性调节作用。老年男性体内雌激素、雄激素的缺乏与其骨密度降低、OP患病率增加都有着密切的关系，性激素及其受体调节剂为OP的治疗提供了新的思路。雌激素是目前女性绝经后骨质疏松（postmenopausal osteoporosis，PMOP）治疗的常用药物，并不被推荐用于治疗男性OP；雄激素替代治疗可使老年男性骨密度得到增加，但在前列腺和心血管安全性上存疑，因而并不推荐常规使用；选择性雌激素受体调节剂（selective estrogen receptor modulator，SERM）能提升血清睾酮水平，有助于增加腰椎和髋关节骨密度，降低骨折风险，但尚未被正式批准用于治疗男性OP，其疗效及安全性有待更多的临床试验来验证；选择性雄激素受体调节剂（selective androgen receptor modulator，SARM）应用于OP的相关研究尚处于起步阶段，目前仅在动物模型中被证实能够增加雄性大鼠的骨骼强度。本文就性激素在老年男性OP发病及治疗中的作用进行回顾和总结，以期为临床医师的工作提供一定参考。     

Evidence that type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency

Type I osteoporosis occurs within 20 years after menopause and is associated with excessive cancellous bone loss and fractures of the vertebrae and distal radius. We have suggested that it may be caused by estrogen deficiency plus some additional factor predisposing to excessive bone loss. One such factor might be a greater degree of sex steroid deficiency, a possibility that could not be previously excluded because assays of sufficient sensitivity have only recently become available. Thus, we studied 36 women with vertebral fractures due to typical high turnover type I postmenopausal osteoporosis and 36 normal postmenopausal women using new ultrasensitive assays with detection limits of 1 pg/ml for estradiol, 5 pg/ml for estrone and 5 ng/dl for testosterone to test if type I osteoporosis results from enhanced responsiveness of bone to estrogen deficiency. Mean levels of serum sex steroids were identical in both groups, but bone turnover was increased by up to 55% in the women with type I osteoporosis. Moreover, compared with controls, the osteoporotic women had a 51% higher (P<0.01) serum osteoprotegerin level, which was likely a compensatory response to the increased bone turnover. In the osteoporotic women, 1-year treatment with transdermal estrogen in 14 women reduced total deoxypyridinoline, an index of bone resorption, by 58% as compared with placebo treatment in 17 women (P<0.001). Thus, as compared to controls, postmenopausal osteoporotic women had comparable sex steroid levels but higher bone turnover levels that were responsive to estrogen therapy. This is consistent with the hypothesis that the greater bone loss in type I osteoporosis is the result of impaired responsiveness of bone to low postmenopausal levels of sex steroids.     

Estrogen deficiency and its effect on the jaw bones

Estrogen deficiency-induced postmenopausal osteoporosis has become a worldwide problem, inducing low bone mass and microarchitectural deterioration of the bone scaffolding in the vertebrae and long bones. With the prevalence of such osteoporosis on the increase, the influence of this estrogen deficiency on the jaw bones has drawn the attention of researchers and clinicians in the field of dentistry. The aim of this article is therefore to review the microstructural changes occurring after ovariectomy in the jaw bones of animal subjects. Induced estrogen deficiency clearly led to structural changes in the jaw bones and alveolar bone of animal subjects (rats and monkeys). Severe bone loss in the rat alveolar bone was principally caused by high bone resorptive activity. This activity accelerated greatly immediately after ovariectomy, and was then followed by more moderate resorptive activity, which continued over an extended period. Additionally, occlusal hypofunction further greatly accelerated the fragility of the alveolar bone structure in ovariectomized rats. Microstructural damage also seen in the alveolar bone of ovariectomized monkeys was found to be directly connected to their systemic osteoporosis. Recent investigations of the relationship in humans between systemic osteoporosis and jaw bone loss have also suggested that a connection may exist between these two. However, more research is required to confirm this connection in humans as well.     

男性雌激素与骨代谢

男性体内的雄激素可经芳香化酶作用转化为雌激素。成骨细胞具有雌激素受体 ,男性骨骼也是雌激素作用的重要靶器官。动物实验和临床研究均证实 ,芳香化酶缺乏或雌激素受体基因突变的男性 ,均可发生骨量减少 ,并形成骨质疏松。雌激素对男性骨骼的生长发育和骨量的保持发挥重要的作用