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 acti on of retinoic acid (RA) on DNA synthesis and on thyroid peroxidase (T PO) and thyroglobulin (TGB) mRNA expression were investigated in prima ry cultures of human thyroid follicular cells. A time and dose-depende nt reduction in H-3-thymidine (H-3-thy) incorporation was found in cel ls exposed for 48 h to all-trans-RA up to 1 muM. A cytotoxic effect wa s found only with the higher dose of 50 muM. The RA-induced decrease o f H-3-thy incorporation was reflected by parallel change in DNA conten t of cell monolayers. The inhibitory effect of 1 muM RA on H-3-thy inc orporation ranged from 28.5 +/- 4.6 % in normal cells to 42 +/-3.2 % i n adenomatous cells. In addition, 1 muM RA significantly reduced basal and TSH-induced TPO mRNA levels in normal, goitrous and adenomatous c ells, but did not alter TGB mRNA levels. Furthermore, in these cells t he study of RAR alpha and beta mRNA showed the presence of two major R AR alpha mRNA transcripts of approximately 3.5 and 2.8 Kb in size, whe reas RAR beta mRNA was undetectable. Overall, our data indicate that R AR alpha gene is expressed in human thyrocytes and that RA may be invo lved in the regulation of the human thyroid by reducing proliferation and function of follicular cells.