Windahl S H, Andersson N, Chagin A S, Mårtensson U E A, Carlsten H, Olde B, Swanson C, Movérare-Skrtic S, Sävendahl L, Lagerquist M K, Leeb-Lundberg L M F, Ohlsson C
Institute of Medicine, Sahlgrenska Academy, Göteborg University, Göteborg.
Am J Physiol Endocrinol Metab. 2009 Mar;296(3):E490-6. doi: 10.1152/ajpendo.90691.2008. Epub 2008 Dec 16.
In vitro studies suggest that the membrane G protein-coupled receptor GPR30 is a functional estrogen receptor (ER). The aim of the present study was to determine the possible in vivo role of GPR30 as a functional ER primarily for the regulation of skeletal parameters, including bone mass and longitudinal bone growth, but also for some other well-known estrogen-regulated parameters, including uterine weight, thymus weight, and fat mass. Three-month-old ovariectomized (OVX) GPR30-deficient mice (GPR30(-/-)) and wild-type (WT) mice were treated with either vehicle or increasing doses of estradiol (E(2); 0, 30, 70, 160, or 830 ng.mouse(-1).day(-1)). Body composition [bone mineral density (BMD), fat mass, and lean mass] was analyzed by dual-energy-X ray absorptiometry, while the cortical and trabecular bone compartments were analyzed by peripheral quantitative computerized tomography. Quantitative histological analyses were performed in the distal femur growth plate. Bone marrow cellularity and distribution were analyzed using a fluorescence-activated cell sorter. The estrogenic responses on most of the investigated parameters, including increase in bone mass (total body BMD, spine BMD, trabecular BMD, and cortical bone thickness), increase in uterine weight, thymic atrophy, fat mass reduction, and increase in bone marrow cellularity, were similar for all of the investigated E(2) doses in WT and GPR30(-/-) mice. On the other hand, E(2) treatment reduced longitudinal bone growth, reflected by decreased femur length and distal femur growth plate height, in the WT mice but not in the GPR30(-/-) mice compared with vehicle-treated mice. These in vivo findings demonstrate that GPR30 is not required for normal estrogenic responses on several major well-known estrogen-regulated parameters. In contrast, GPR30 is required for a normal estrogenic response in the growth plate.
体外研究表明，膜G蛋白偶联受体GPR30是一种功能性雌激素受体（ER）。本研究的目的是确定GPR30作为功能性ER在体内可能发挥的作用，主要用于调节骨骼参数，包括骨量和纵向骨生长，也用于调节其他一些众所周知的雌激素调节参数，包括子宫重量、胸腺重量和脂肪量。对3月龄卵巢切除（OVX）的GPR30基因缺陷小鼠（GPR30(-/-)）和野生型（WT）小鼠，分别给予溶媒或递增剂量的雌二醇（E2；0、30、70、160或830 ng·小鼠-1·天-1）进行处理。采用双能X线吸收法分析身体成分[骨矿物质密度（BMD）、脂肪量和瘦体重]，同时采用外周定量计算机断层扫描分析皮质骨和小梁骨部分。对股骨远端生长板进行定量组织学分析。使用荧光激活细胞分选仪分析骨髓细胞数量和分布。对于WT和GPR30(-/-)小鼠中所有研究的E2剂量，在大多数研究参数上的雌激素反应相似，包括骨量增加（全身BMD、脊柱BMD、小梁BMD和皮质骨厚度）、子宫重量增加、胸腺萎缩、脂肪量减少和骨髓细胞数量增加。另一方面，与溶媒处理的小鼠相比，E2处理降低了WT小鼠的纵向骨生长，表现为股骨长度和股骨远端生长板高度降低，但在GPR30(-/-)小鼠中未出现这种情况。这些体内研究结果表明，在几个主要的、众所周知的雌激素调节参数上，正常的雌激素反应不需要GPR30。相反，生长板中的正常雌激素反应需要GPR30。
