INTERFERENCE BETWEEN ESTRADIOL AND L-TRIIODOTHYRONINE IN THE CONTROL OF THE PROLIFERATION OF A PITUITARY-TUMOR CELL-LINE

We showed that the proliferation of F4Z2 cells, established from a rat pituitary tumor, was stimulated by L-triiodothyronine (LT3) in the pr esence of 3 or 0.1 % charcoal treated-fetal calf serum (CT-FCS), and b y estradiol (E2) in the presence of 3 % CT-FCS only (Cancer Res., 50, 1990, 3786). Here we report on the consequences of the simultaneous ad dition of these hormones. In the presence of 0. 1 % CT-FCS, E2, and wi th a lower potency, estrone and estriol inhibited dose-dependently sti mulation by LT3. The results were more complex with 3 % CT-FCS: the LT 3 effect was blunted by E2 > 0. 1 nM (and vice versa) and the hormone effects were additive at lower concentrations. E2, at concentrations a ntagonistic to the effects of LT3, decreased LT3 binding and LT3 recep tor mRNA without modifying the effect of LT3 on these mRNAs. In additi on, E2 blocked both the LT3-induced increases of insulin-like growth f actor-I (IGF-I) secretion and IGF-I mRNA concentration, and the LT3-in duced decrease of IGF-binding proteins in conditioned culture medium. We propose that E2 prevents LT3 stimulation of F4Z2 cell proliferation by blunting the LT3-induced accumulation of unbound IGF-I in the cult ure medium.