SITE SELECTIVITY OF OSTEOBLAST GENE-EXPRESSION RESPONSE TO THYROID-HORMONE LOCALIZED BY IN-SITU HYBRIDIZATION

We have previously reported that thyroid-stimulating hormone (TSH)-sup pressive sive doses of L-thyroxine (L-T-4) decrease femoral, but not v ertebral, bone mineral density (BMD) in rats. L-T-4-induced decreases in BMD were associated with increased expression of genes, reflecting osteoblast activity in mRNA extracted from whole femurs but not from v ertebrae. To document that this skeletal selectivity reflected altered osteoblast activity, we studied gene expression by in situ hybridizat ion in 8-wk-old rats treated with L-T-4 (20 mu g . 100 g body wt(-1) . day(-1)) for 4 wk. TSH-suppressive doses of L-T-4 were associated wit h decreased femoral (0.299 +/- 0.005 vs. 0.273 +/- 0.005 g/cm(2), P < 0.01), but not vertebral (0.222 +/- 0.004 vs. 0.218 +/- 0.003 g/cm(2)) , BMD. In situ hybridization documented that L-T-4 administration for 4 wk increased expression of osteocalcin and alkaline phosphatase mRNA in femoral, but not vertebral, osteoblasts. This study demonstrates a differential gene expression response of vertebral and femoral osteob lasts to L-T-4. This altered degree of gene expression markers of oste oblast activity documented by in situ hybridization may in part explai n the apparent clinical differences in the effect of L-T-4 on femoral and vertebral BMD.