TY - JOUR AU - Lakatos, Péter AU - Stern, P H TI - Effects of cyclosporins and transforming growth factor β1 on thyroid hormone action in cultured fetal rat limb bones JF - CALCIFIED TISSUE INTERNATIONAL J2 - CALCIFIED TISSUE INT VL - 50 PY - 1992 IS - 2 SP - 123 EP - 128 PG - 6 SN - 0171-967X DO - 10.1007/BF00298788 UR - https://m2.mtmt.hu/api/publication/1802377 ID - 1802377 N1 - Manufacturers: sandoz, United States; sigma, United States; smith kline beecham, United States AB - To study the mechanism of action of thyroid hormones on bone, we examined the effects of immunosuppressive 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. LA - English DB - MTMT ER - TY - JOUR AU - Lakatos, Péter AU - Stern, P H TI - Evidence for direct non-genomic effects of triiodothyronine on bone rudiments in rats: Stimulation of the inositol phosphate second messenger system JF - ACTA ENDOCRINOLOGICA J2 - ACTA ENDOCRINOL VL - 125 PY - 1991 IS - 5 SP - 603 EP - 608 PG - 6 SN - 0001-5598 DO - 10.1530/acta.0.1250603 UR - https://m2.mtmt.hu/api/publication/1802379 ID - 1802379 AB - Thyroid hormones increase cytosolic free calcium by binding to plasma membrane receptors in several tissues. This calcium increase appears to initiate extranuclear effects in these tissues. Increases in cytosolic calcium are often a consequence of stimulation of inositol phosphate second messenger pathway. Several calcemic hormones act via this signal transduction route. Therefore we investigated the effects of the metabolically active T3 and the inactive analogues 3,5-diiodotyrosine and rT3 on the inositol phosphate pathway in fetal rat limb bone cultures prelabeled with [3H]myoinositol. Labelled inositol and inositol phosphates were separated by HPLC. There was a significant increase in the radioactivity in inositol bis- and trisphosphates after 1 min of exposure to 10-7 mol/l T3. Stimulation was also observed at 10-6 mol/l T3, but not at 10-5 mol/l. Time course studies demonstrated a rapid effect of T3 on inositol phosphates within 30 seconds that lasted through 5 min. After 20 min incubation with T3, no increase was observed in inositol mono- and bisphoshates, and a decrease was seen in inositol trisphosphate. Pretreatment with indomethacin prevented these effects of T3. 3,5-diiodothyrosine and rT3 did not affect inositol phosphate metabolism. These results suggest the existence of plasma membrane-associated receptors for T3 in bone, in addition to the nuclear receptors demonstrated previously. The role of these receptors in the effects of thyroid hormones on bone remains to be established. LA - English DB - MTMT ER -