Comparative and Molecular Endocrinology Group, Centre for Marine Sciences (CCMAR), Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
Gen Comp Endocrinol. 2012 Dec 1;179(3):421-7. doi: 10.1016/j.ygcen.2012.09.018. Epub 2012 Oct 1.
In teleosts the regulation of skeletal homeostasis and turnover by estrogen is poorly understood. For this reason raloxifene, a selective estrogen-receptor modulator (SERM), was administered to sea bream (Sparus auratus) and its effect on plasma calcium balance and transcript expression in dentary (dermal bone) and vertebra (perichondral bone) was studied. The concentration of total calcium or phosphorus in plasma was unchanged by raloxifene treatment for 6days. The activity of alkaline phosphatase (ALP) in dentary bone of raloxifene treated fish was significantly (p<0.05) higher than control fish but it was not changed in vertebral bone. Transcripts for estrogen receptor (ER) α were in very low abundance in the sea bream dentary and vertebra and were unchanged by raloxifene treatment. In contrast, raloxifene caused significant (p<0.05) up-regulation of the duplicate ERβ transcripts in the dentary but did not affect specific transcripts for osteoclast (TRAP), osteoblast (ALP, Runx2, osteonectin) or cartilage (IGF1, CILP2, FN1a). In the vertebra ERβb was not changed by raloxifene but ERβa was significantly (p<0.05) down-regulated as was the skeletal specific transcripts, TRAP, ALP, CILP2, FN1a. In summary, ERβs regulate estrogen sensitivity of the skeleton in sea bream, which responds in a non uniform manner. In common with mammals raloxifene appears to have an anti-resorptive role (in sea bream vertebra), but also an osteoblast stimulatory role, inducing ALP activity in the dentary of sea bream. Overall, the results indicate bone specific responsiveness to raloxifene in the sea bream. Further work will be required to understand the basis of bone responsiveness and the role of E(2) and ERs in teleost bone homeostasis.
在硬骨鱼中，雌激素对骨骼动态平衡和转换的调节作用还知之甚少。出于这个原因，给真鲷（Sparus auratus）投喂了雷洛昔芬，一种选择性雌激素受体调节剂（SERM），并研究了其对血浆钙平衡和齿状骨（真皮骨）和椎骨（软骨骨）转录表达的影响。6 天的雷洛昔芬处理并没有改变血浆中总钙或磷的浓度。雷洛昔芬处理鱼的齿状骨碱性磷酸酶（ALP）活性显著（p<0.05）高于对照组，但软骨骨中的 ALP 活性没有变化。真鲷的齿状骨和椎骨中雌激素受体（ER）α的转录本含量非常低，并且雷洛昔芬处理没有改变。相比之下，雷洛昔芬导致齿状骨中 ERβ 的重复转录本显著（p<0.05）上调，但不影响破骨细胞（TRAP）、成骨细胞（ALP、Runx2、骨桥蛋白）或软骨细胞（IGF1、CILP2、FN1a）的特异性转录本。在椎骨中，雷洛昔芬没有改变 ERβb，但 ERβa 显著（p<0.05）下调，骨骼特异性转录本 TRAP、ALP、CILP2、FN1a 也是如此。总之，ERβs 调节真鲷骨骼对雌激素的敏感性，其反应方式不一致。与哺乳动物一样，雷洛昔芬似乎具有抗吸收作用（在真鲷的椎骨中），但也具有成骨细胞刺激作用，诱导真鲷齿状骨的 ALP 活性。总的来说，这些结果表明，真鲷对雷洛昔芬具有骨骼特异性反应。需要进一步的研究来了解骨骼对雷洛昔芬的反应基础以及 E2 和 ERs 在硬骨鱼骨骼动态平衡中的作用。
