Thyroid hormones increase insulin-like growth factor I content in the medium of rat bone tissue.
The mechanism of action of thyroid hormones on bone is still not clear. At low concentrations, they stimulate bone formation; at high concentrations, they elicit bone resorption in vitro and in vivo. In the present study we investigated the effect of T3 and T4 as well as their active and inactive analogs (TRIAC, SKF L-94901, rT3, and DIT) on the IGF-I and TNF-alpha content in the medium of UMR-106 rat osteoblastic cells 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, with peak stimulatory concentrations of 10(-8) M for T3 and 10(-7) M for T4 in both systems. At higher concentrations, at which thyroid hormones elicit bone resorption, the stimulatory effect diminished and finally 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 content of the cell culture wells exposed to high concentrations of thyroid hormones was similar to those containing low concentrations, indicating 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 medium IGF-I after 2 days of incubation. No significant further increase was observed after this up to 5 days of culture.(ABSTRACT TRUNCATED AT 250 WORDS)
Lakatos
P
P
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois.
Caplice
M D
MD
Khanna
V
V
Stern
P H
PH
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D003470:Culture Media; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005121:Extremities; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000494:pharmacology*; D013970:Thyronines / Q000494:pharmacology; D013974:Thyroxine / Q000494:pharmacology; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000494:pharmacology; D014285:Triiodothyronine, Reverse / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003470:Culture Media; C050835:SK&F 94901; D013963:Thyroid Hormones; D013970:Thyronines; D014409:Tumor Necrosis Factor-alpha; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; D014285:Triiodothyronine, Reverse; D007334:Insulin-Like Growth Factor I; D013974:Thyroxine