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Effects of Retinoids on Iodine Metabolism, Thyroid Peroxidase Gene Expression, and Deoxyribonucleic Acid Synthesis in Porcine Thyroid Cells in Culture^*

Institute for Growth Science Tokyo 162, Japan
Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women’s Medical College Tokyo 162, Japan

Address all correspondence and requests for reprints to: Dr. Toshio Tsushima, Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women’s Medical College, 8–1 Kawada-cho, Shinjuku-ku, Tokyo 162, Japan.

Abstract

Effects of retinoids on DNA synthesis, iodine metabolism, and thyroid peroxidase messenger RNA levels were studied in cultured porcine thyroid cells. Retinol (10^–8-10^–5 M) alone did not affect DNA synthesis but potentiated that induced by epidermal growth factor or insulin-like growth factor-I without changes in the number or affinity of receptors for the growth factors, suggesting that retinol stimulates postreceptor events responsible for DNA synthesis. Retinol was an inhibitor of TSHstimulated iodine metabolism. Iodide uptake and release of organified iodine stimulated by TSH or forskolin were inhibited dose dependently by treatment with retinol. The inhibition was detected at 10^–8 M and was approximately 50% at 10^–6 M. The potency of retinoic acid was comparable to that of retinol. The inhibitory effect of retinol was detected after treatments of thyroid cells for 24 h, and the maximal effect occurred after 48 h incubation. The cAMP accumulation in cultures treated with TSH plus retinol was lower than that of control cultures treated with TSH alone. However, iodide uptake stimulated by 8-bromocAMP was also inhibited by retinoids. Retinol reduced TSH- or 8-bromo-cAMP-stimulated gene expression of thyroid peroxidase. Thus, the data suggest that retinoids inhibit TSH-stimulated iodine metabolism by reducing cAMP accumulation and also by acting on the steps subsequent to cAMP production. (Endocrinology 129: 2827–2833, 1991)

Footnotes

^* This work was supported by grants from the Ministry of Health and Welfare and the Ministry of Education of Japan.

Received April 22, 1991.

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