Site selectivity of osteoblast gene expression response to thyroid
hormone localized by in situ hybridization.
Suwanwalaikorn, S., M. Van Auken, Moo-Il Kang, S. Alex, L. E.
Braverman, and D. T. Baran.
Departments of Medicine and Orthopedics, University of
Massachusetts Medical Center, 55 Lake Avenue North, Worcester, MA
01655, Tel: (508) 856-2739, FAX: (508) 856-5916
APStracts 3:0198E, 1996.
We have previously reported that 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-week-old rats
treated with L-T4, 20 [mu]g/100 g body weight/day, for 4 weeks. 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 weeks
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.
Received 15 April 1996; accepted in final form 13 September 1996.
APS Manuscript Number E188-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996