P. Lakatos et al., THYROID-HORMONES INCREASE INSULIN-LIKE GROWTH FACTOR-I CONTENT IN THEMEDIUM OF RAT BONE TISSUE, Journal of bone and mineral research, 8(12), 1993, pp. 1475-1481
The mechanism of action of thyroid hormones on bone is still not clear
. At low concentrations, they stimulate bone formation; at high concen
trations, they elicit bone resorption in vitro and in vivo. In the pre
sent study we investigated the effect of T3 and T3 as well as their ac
tive and inactive analogs (TRIAC, SKF L-94901, rT3, and DIT) on the IG
F-I and TNF-alpha content in the medium of UMR-106 rat osteoblastic ce
lls and fetal rat limb bones. In the dose-response studies, a biphasic
increase in medium IGF-I was observed in both cells and limb bones, w
ith peak stimulatory concentrations of 10(-8) M for T3 and 10(-7) M fo
r T4 in both systems. At higher concentrations, at which thyroid hormo
nes elicit bone resorption, the stimulatory effect diminished and fina
lly was no longer detectable. The active analogs TRIAC and SKF L-94901
also enhanced IGF-I release in UMR-106 cells. The inactive compounds
rT3 and DIT failed to increase IGF-I in these cultures. The protein co
ntent of the cell culture wells exposed to high concentrations of thyr
oid hormones was similar to those containing low concentrations, indic
ating that the decrease in IGF-I content at high doses was not due to
toxic effects. This was also confirmed by trypan blue exclusion. Time
course studies with UMR-106 cells revealed a significant increase in m
edium IGF-I after 2 days of incubation. No significant further increas
e was observed after this up to 5 days of culture. In contrast, the me
dium of limb bone cultures showed a linear increase in IGF-I content u
p to 7 days of culture. No TNF-alpha production was observed in either
UMR-106 cells or fetal limb bones. Also, no increase in medium TNF-al
pha levels was seen in response to thyroid hormones. Based on our resu
lts, we conclude that IGF-I may be responsible for some of the anaboli
c effects of thyroid hormones in bone tissue, but TNF-alpha, at least
in the models we used, does not play a role in the mediation of thyroi
d hormone action.