The effects of thyroid hormones on estrogen receptor (ER) levels in four different rat pituitary clonal cell lines designated as MtT/Se, SM, S and E, were investigated. When T-3 was added at 10(-7) M, a significant increase in ER was evident after 9 h with maximum levels reached after 24-48 h in MtT/Se (270% of control), MtT/SM (160%) and MtT/S (140%). No significant increase was noted in MtT/E cells in which the T-3 receptor (T3R) level was only one-tenth of that in the other cells, suggesting a direct link between ER expression and T3R binding. ER levels began to increase at 10(-10) M and reached maxima at 10(-8) M in MtT/Se, SM and S cells. Up to 10(-5) M of retinoic acid (RA) did not change ER levels in any of the cell lines. When Se cells were treated with cycloheximide before T-3 administration, the increase in ER was completely blocked. Northern blot analysis of total RNA isolated from T-3-treated MtT/Se cells revealed a limited 1.4-fold increase in ER mRNA at 10(-7) M. In conclusion, thyroid hormones (but not RA) increase ER levels in pituitary cells by a process requiring protein synthesis, and which is accompanied by an increase in the mRNA. (C) 1997 Elsevier Science Ltd.