The novel estrogen receptor G-protein-coupled receptor 30 is expressed in human bone

Estrogens have significant impact on bone mineral metabolism. Besides the classical estrogen receptors (ER alpha and ER beta), a trans-membrane G-protein-coupled receptor (GPR30) has been demonstrated to mediate estrogenic effects. We aimed to study whether GPR-30 is expressed in bone cells and if so, whether the level of expression is developmentally regulated. Metaphyseal bone biopsies were collected from the tibia in 14 boys and 6 girls, all at different stages of puberty. GPR30 protein expression was studied by immunohistochemistry in paraffin-embedded sections. GPR30-positive osteocytes and osteoblasts were quantified and linear regression analysis was applied. Cyto-plasmic GPR30 expression was detected in osteoblasts, osteocytes, and osteoclasts. Osteocytes were more frequently positive for GPR30 than osteoblasts (58 +/- 4% vs 46 +/- 3% positive cells respectively, P<0-05). Detailed analysis demonstrated that GPR30 positivity declined during pubertal development in osteocytes (R=-0.56, P<0.01) but not in osteoblasts (R=-0.31, P>0.05). No sex difference was observed in the numbers of GPR30-positive osteoblasts or osteocytes. Furthermore, GPR30 expression did not correlate with chronological or bone age. In conclusion, the novel ER GPR30 is expressed in osteoblasts, osteocytes, and osteoclasts suggesting that non-genomic estrogen signaling via GPR30 may exist in bone. However, the functional role of GPP30 in bone tissue remains to be elucidated.