The role of hypothalamic estrogen receptors in metabolic regulation

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ‘classical’ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1^−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism.     

Effects of Estrogen Deficiency and/or Caffeine Intake on Alveolar Bone Loss,Density, and Healing: A Study in Rats

Background: The aim of this study is to evaluate the effects of caffeine and/or estrogen deficiency on ligature‐induced bone loss (BL), trabecular bone area (TBA), and postextraction bone healing (BH). Methods: Rats were assigned into one of the following groups (15 each): 1) control = non‐ingestion of caffeine/sham surgery; 2) caffeine = ingestion of caffeine/sham surgery); 3) ovariectomized (OVX) = non‐ingestion of caffeine/ovariectomy; or 4) caffeine/OVX = ingestion of caffeine/ovariectomy. The rats were under caffeine administration for 65 days and/or estrogen deficiency for 51 days. On day 21 after ovariectomy, one first mandibular molar received a ligature and the contralateral tooth was not ligated. The first maxillary molars were extracted 8 days before sacrifice. BL, TBA, the positive cells for tartrate‐resistant acid phosphatase (TRAP), receptor activator of nuclear factor‐κB ligand (RANKL), and osteoprotegerin (OPG) were analyzed in the furcation area of mandibular molars. Histometric BH and gene expression of bone morphogenetic protein (BMP)‐2, BMP‐7, osteopontin, and bone sialoprotein were evaluated in alveolar sockets. Results: The caffeine group presented the greatest BL and the OVX group the highest number of TRAP‐positive (TRAP⁺) cells around ligated teeth (P <0.05). The control group presented higher TBA and BH than the other groups (P <0.05). All test groups presented higher RANKL/OPG⁺ cells than the control group around ligated/unligated teeth. The OVX and caffeine/OVX groups presented a greater number of TRAP⁺ cells around unligated teeth than the control group (P <0.05). There were no differences among groups for gene expression (P >0.05). Conclusions: Caffeine increased BL in ligated teeth. Caffeine and/or estrogen deficiency decreased TBA in the unligated teeth and reduced BH after tooth extraction.     

骨质疏松症动物模型研究进展

骨质疏松症(osteoporosis,OP)是一种临床上常见的以骨量减少和骨组织微观结构破坏为特点,从而导致骨脆性增加、易于发生骨折的全身代谢性疾病。随着人口老龄化进程的加速,骨质疏松症尤其是绝经后骨质疏松症的发生率逐渐上升,骨质疏松症在医学上和社会性的影响逐渐加深。人类骨质疏松症主要有糖皮质激素相关型、绝经后骨质疏松症以及失用型、老年性骨质疏松症几种类型。糖皮质激素相关型骨质疏松症动物模型利用糖皮质激素诱导建立,其降低成骨细胞的活性、刺激破骨细胞,从而减少骨形成、增加骨吸收。利用去势法建立绝经后骨质疏松动物模型,其原理是雌激素减少致使骨吸收增加、新骨形成降低,最终达到骨量减少的目的。雌激素受体α诱导破骨细胞凋亡,但是阻碍成骨细胞功能的机制目前尚不明确。SAM-P6(Senescence-accelerated mouse-P6)是一种衰老加速的小鼠,骨丢失随年龄增长而增加,适用于老年型骨质疏松动物模型。失用型骨质疏松动物模型常见的建模方法有坐骨神经切除法、悬吊法等,机体长期处于无重力负荷状态,使得破骨细胞活性相对增加,导致骨量丢失。笔者就不同种类动物作为骨质疏松症研究模型的优缺点、绝经后骨质疏松症动物模型中对不同部位骨骼的影响作简要概述。     

Promotion of normal healing of bone defects under estrogen deficiency by implantation of beta‐tricalcium phosphate composed of rod‐shaped particles

We compared the healing of bone defects in ovariectomized rats implanted with beta‐tricalcium phosphate (β‐TCP) composed of rod‐shaped particles, which were prepared using the applied hydrothermal method (HTCP), and that of bone defects implanted with conventional β‐TCP composed of globular‐shaped particles (CTCP), which were prepared by normal sintering. Eight‐week‐old female Wistar rats were ovariectomized, and 2 weeks after the operation, 0.5‐ to 0.6‐mm diameter spherical granules of each ceramic were implanted in a bone defect created in the distal end of the femur. Four, 8, and 12 weeks after implantation, the amount of newly formed bone implanted with HTCP was significantly larger than that implanted with CTCP and was equivalent to that in non‐ovariectomized sham‐operated rats. Without implantation, spontaneous repair of the trabecular bone was barely observed. The physiological structure of the trabecular network was maintained in the region implanted with HTCP, but that in the region implanted with CTCP was severely destroyed. Gene expression microarray analysis revealed that the expression of genes involved in interferon signaling pathways was upregulated in osteoclasts cultured on HTCP compared with that cultured on CTCP. Our results suggest that the microstructure of β‐TCP affected the biological behavior of osteoclasts and regulated local bone metabolism. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:189–196, 2014.     

Endothelial and neuronal nitric oxide synthases variably modulate the oestrogen‐mediated control of blood pressure and cardiovascular autonomic control

相似文献   

去势大鼠骨质疏松性骨小梁的压缩断裂仿真

文题释义： 原发性骨质疏松症：是一种以骨量降低、骨微结构破坏、骨脆性增加、骨折风险性增大为特征的全身性骨骼系统疾病,其多发于老年人,尤以绝经后妇女多见。 断裂：材料或构件力学性能的基本表征。根据断裂前发生的塑性变形的大小,可把材料的断裂分为脆性断裂和延性断裂两大类。随材料和条件的不同,循环载荷作用下的疲劳断裂、高温下的蠕变断裂以及环境作用下的应力腐蚀断裂,均可表现为脆性断裂和延性断裂。 背景：目前已有相关有限元模型仿真模拟了股骨骨折,并探讨了载荷速率、载荷角度及松质骨在髋部骨折中的影响,但骨小梁的断裂仿真仍缺乏相关研究。 目的：仿真模拟去势大鼠骨质疏松性骨小梁压缩断裂的生物力学过程。 方法：取去势大鼠右侧股骨于Micro-CT扫描股骨远端,获得大鼠股骨感兴趣区域骨微结构参数及三维模型,在Geomagic Studio几何优化后在Hypermesh 14.0前处理,包括体网格划分、设置材料属性参数、边界条件,设置载荷1 200 N,作用时间2 ms,在LS-DYNA软件中进行运算。 结果与结论：①感兴趣区域骨小梁显示空间分布不均;②骨小梁体积小、数量少的部位最先开始出现变形断裂,板状及较大体积的骨小梁最后发生断裂塌陷;③Von-mises应力变化趋势与骨小梁断裂塌陷趋势大致相同;④感兴趣区域骨小梁断裂塌陷过程包括了垂直塌陷和水平扭转,其中水平扭转程度及速率低于垂直塌陷,使得横断面扭转成角大小及成角速率小于冠状面成角;⑤破坏单元的剪切应力增幅及峰值较Von-mises应力小;⑥提示骨小梁断裂塌陷是个复杂的过程,包含了不同平面的变形、成角。 ORCID: 0000-0002-5792-3012(吴宇航) 中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程     

Effects of estrogen deficiency and low bone mineral density on healthy knee cartilage in rabbits

The purpose of this study was to compare the effects of estrogen deficiency and bone mass loss on normal knee cartilage in mature rabbits. Bilateral ovariectomy (OVX) was performed in 13 rabbits, 6 of which also received systemic glucocorticoid for 4 weeks. Seven additional healthy rabbits were used as controls. Bone mineral density (BMD) was measured by dual X‐ray absorptiometry in lumbar spine, knee, and subchondral bone of the knee at baseline and 22 weeks after OVX. After sacrifice, the knees were dissected, macroscopy was assessed, and histological cartilage abnormalities were evaluated according to the Mankin score. Correlations of Mankin with BMD at different regions were also performed. When compared to baseline, differences in BMD were only found in spine and knee of the animals receiving glucocorticoids. All the animals subjected to OVX had a significantly higher Mankin score than controls. Mankin was upper in OVX animals receiving glucocorticoids, but differences were not significant. The Mankin score was inversely related with BMD in lumbar spine (r = ?0.67; p < 0.01). Although low bone mineral density contributes to the minor osteoarthritic alterations observed in our model, estrogen deficiency itself seems to act directly to induce the main pathogenic effects in healthy cartilage of the rabbit. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:812–818, 2010     

雌激素对卵巢切除后雌性大鼠心肌组织中雌激素受体表达的影响

目的：探讨雌激素对卵巢切除后雌性大鼠心肌组织中雌激素受体表达的影响。方法：雌性SD大鼠卵巢切除术（OVX）后1周,随机分成3组：OVX＋雌激素（0.15mg/kg,s.c.）、OVX＋生理盐水、对照组。4周后,Westernblotting检测α和β两种雌激素受体在心肌组织中的表达。结果：卵巢切除后,血清雌激素水平与对照组[（88±22vs403±59）pmol/L,P〈0.05]相比明显下降,左心室肌中两种雌激素受体表达均下降（P〈0.05）。给予雌激素后,血清雌激素水平上升为（3864±105）pmol/L,雌激素β受体表达增多（P〈0.05）,α受体表达下降（P〈0.05）。结论：雌激素改变卵巢切除后雌性大鼠心肌组织中雌激素受体的表达。