AJP - Endocrinology and Metabolism, Vol 272, Issue 2 E212-E217, Copyright © 1997 by American Physiological Society
Site selectivity of osteoblast gene expression response to thyroid hormone localized by in situ hybridization
S. Suwanwalaikorn, M. Van Auken, M. I. Kang, S. Alex, L. E. Braverman and D. T. Baran
Department of Medicine, University of Massachusetts Medical Center, Worcester 01655, USA.
We have previously reported that thyroid-stimulating hormone
(TSH)-suppressive doses of L-thyroxine (L-T4) decrease femoral, but not
vertebral, bone mineral density (BMD) in rats. L-T4-induced decreases in
BMD were associated with increased expression of genes, reflecting
osteoblast activity in mRNA extracted from whole femurs but not from
vertebrae. To document that this skeletal selectivity reflected altered
osteoblast activity, we studied gene expression by in situ hybridization in
8-wk-old rats treated with L-T4 (20 microg x 100 g body wt(-1) x day(-1))
for 4 wk. TSH-suppressive doses of L-T4 were associated with decreased
femoral (0.299 +/- 0.005 vs. 0.273 +/- 0.005 g/cm2, P < 0.01), but not
vertebral (0.222 +/- 0.004 vs. 0.218 +/- 0.003 g/cm2), BMD. In situ
hybridization documented that L-T4 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 osteoblasts to L-T4. This
altered degree of gene expression markers of osteoblast activity documented
by in situ hybridization may in part explain the apparent clinical
differences in the effect of L-T4 on femoral and vertebral BMD.
