RETINOIC ACID-INDUCED DECREASE OF DNA-SYNTHESIS AND PEROXIDASE MESSENGER-RNA LEVELS IN HUMAN THYROID-CELLS EXPRESSING RETINOIC ACID RECEPTOR-ALPHA

In order to clarify the effect of retinoids on thyroid cell growth and function, the presence of retinoic acid receptors (RARs) and the action of retinoic acid (RA) on DNA synthesis and on thyroid peroxidase (TPO) and thyroglobulin (TGB) mRNA expression were investigated in primary cultures of human thyroid follicular cells. A time and dose-dependent reduction in H-3-thymidine (H-3-thy) incorporation was found in cells exposed for 48 h to all-trans-RA up to 1 muM. A cytotoxic effect was found only with the higher dose of 50 muM. The RA-induced decrease of H-3-thy incorporation was reflected by parallel change in DNA content of cell monolayers. The inhibitory effect of 1 muM RA on H-3-thy incorporation ranged from 28.5 +/- 4.6 % in normal cells to 42 +/-3.2 % in adenomatous cells. In addition, 1 muM RA significantly reduced basal and TSH-induced TPO mRNA levels in normal, goitrous and adenomatous cells, but did not alter TGB mRNA levels. Furthermore, in these cells the study of RAR alpha and beta mRNA showed the presence of two major RAR alpha mRNA transcripts of approximately 3.5 and 2.8 Kb in size, whereas RAR beta mRNA was undetectable. Overall, our data indicate that RAR alpha gene is expressed in human thyrocytes and that RA may be involved in the regulation of the human thyroid by reducing proliferation and function of follicular cells.