Seriwatanachai Dutmanee, Thongchote Kanogwun, Charoenphandhu Narattaphol, Pandaranandaka Jantarima, Tudpor Kukiat, Teerapornpuntakit Jarinthorn, Suthiphongchai Tuangporn, Krishnamra Nateetip
Department of Physiology, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
Bone. 2008 Mar;42(3):535-46. doi: 10.1016/j.bone.2007.11.008. Epub 2007 Nov 29.
Hyperprolactinemia leads to high bone turnover as a result of enhanced bone formation and resorption. Although its osteopenic effect has long been explained as hyperprolactinemia-induced hypogonadism, identified prolactin (PRL) receptors in osteoblasts suggested a possible direct action of PRL on bone. In the present study, we found that hyperprolactinemia induced by anterior pituitary transplantation (AP), with or without ovariectomy (Ovx), had no detectable effect on bone mineral density and content measured by dual-energy X-ray absorptiometry (DXA). However, histomorphometric studies revealed increases in the osteoblast and osteoclast surfaces in the AP rats, but a decrease in the osteoblast surface in the AP+Ovx rats. The resorptive activity was predominant since bone volume and trabecular number were decreased, and the trabecular separation was increased in both groups. Estrogen supplement (E2) fully reversed the effect of estrogen depletion in the Ovx but not in the AP+Ovx rats. In contrast to the typical Ovx rats, bone formation and resorption became uncoupled in the AP+Ovx rats. Therefore, hyperprolactinemia was likely to have some estrogen-independent and/or direct actions on bone turnover. Osteoblast-expressed PRL receptor transcripts and proteins shown in the present study confirmed our hypothesis. Furthermore, we demonstrated that the osteoblast-like cells, MG-63, directly exposed to PRL exhibited lower expression of alkaline phosphatase and osteocalcin mRNA, and a decrease in alkaline phosphatase activity. The ratios of receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) proteins were increased, indicating an increase in the osteoclastic bone resorption. The present data thus demonstrated that hyperprolactinemia could act directly on bone to stimulate bone turnover, with more influence on bone resorption than formation. PRL enhanced bone resorption in part by increasing RANKL and decreasing OPG expressions by osteoblasts.
高催乳素血症由于骨形成和吸收增强导致骨转换率升高。尽管其骨质减少作用长期以来被解释为高催乳素血症诱导的性腺功能减退，但成骨细胞中已鉴定出的催乳素（PRL）受体提示PRL可能对骨有直接作用。在本研究中，我们发现通过垂体前叶移植（AP）诱导的高催乳素血症，无论是否进行卵巢切除术（Ovx），对双能X线吸收法（DXA）测量的骨矿物质密度和含量均无明显影响。然而，组织形态计量学研究显示，AP大鼠的成骨细胞和破骨细胞表面增加，但AP + Ovx大鼠的成骨细胞表面减少。由于两组的骨体积和骨小梁数量减少，骨小梁间距增加，故吸收活性占主导。雌激素补充剂（E2）完全逆转了Ovx大鼠雌激素缺乏的影响，但对AP + Ovx大鼠无效。与典型的Ovx大鼠不同，AP + Ovx大鼠的骨形成和吸收出现解偶联。因此，高催乳素血症可能对骨转换有一些雌激素非依赖性和/或直接作用。本研究中显示的成骨细胞表达的PRL受体转录本和蛋白证实了我们的假设。此外，我们证明直接暴露于PRL的成骨样细胞MG - 63碱性磷酸酶和骨钙素mRNA表达降低，碱性磷酸酶活性下降。核因子κB受体活化因子配体（RANKL）与骨保护素（OPG）蛋白的比例增加，表明破骨细胞性骨吸收增加。因此，本研究数据表明高催乳素血症可直接作用于骨以刺激骨转换，对骨吸收的影响大于骨形成。PRL部分通过增加成骨细胞RANKL表达和降低OPG表达来增强骨吸收。
