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Effects of cyclosporins and transforming growth factor β1 on thyroid hormone action in cultured fetal rat limb bones

  • Clinical Investigations
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Summary

To study the mechanism of action of thyroid hormones on bone, we examined the effects of immunosuppresive and nonimmunosuppressive cyclosporins, as well as of transforming growth factor β1 (TGFβ1), 17β-estradiol (E2), and dihydroxytestosterone (DHT) on thyroxine (T4)-and triiodothyronine (T3)-stimulated bone resorption in fetal rat limb bones. The immunosuppressive cyclosporins A (CsA) and G (CsG) inhibited thyroid hormone (T4+T3)-stimulated resorption and β-glucuronidase release into the culture medium, whereas the weak or nonimmunosuppressive cyclosporins D (CsD) and H (CsH) did not show this effect. Increasing the medium calcium concentration reduced the ability of T4 to stimulate 45Ca release, while not significantly affecting the response to CsA. TGFβ1 elicited a biphasic effect when administered together with T4. During the first 3 days of culture, TGFβ1 elicited a small, nonsignificant decrease in released 45Ca; during a subsequent 3 days of culture, it enhanced T4-stimulated bone resorption significantly. These effects differed from those of TGFβ1 on parathormone-stimulated resorption. E2 and DHT did not influence the action of T4 on bone tissue. These results suggest that the mechanism of action of thyroid hormones on bone may involve immune factors, as well.

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  1. Department of Pharmacology, Northwestern University Medical School, 303 East Chicago Ave., 60611, Chicago, Illinois, USA

    Peter Lakatos & Paula H. Stern

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  1. Peter Lakatos
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  2. Paula H. Stern
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Lakatos, P., Stern, P.H. Effects of cyclosporins and transforming growth factor β1 on thyroid hormone action in cultured fetal rat limb bones. Calcif Tissue Int 50, 123–128 (1992). https://doi.org/10.1007/BF00298788

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  • DOI: https://doi.org/10.1007/BF00298788

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