Triiodothyronine Regulates Insulin-Like Growth Factor-I Binding to Cultured Rat Pituitary Cells*

Triiodothyronine (T₃) stimulates the synthesis of growth hormone and enhances the growth of neoplastic rat pituitary somatomam-motrophs (GH cells) in culture. Moreover, T₃ has been shown to stimulate the production and secretion of an autocrine growth factor by these cells. We have previously demonstrated the presence of specific receptors for insulin-like growth factors (IGF) on GH cells. Since GH₃ cells contain mRNA encoding IGF-I, it has been suggested that IGF-I might act in an autocrine fashion in these cells. Therefore, it was of interest to learn how T₃ affects IGF-I binding to GH₃ cells. T₃ increased [¹²⁵I]IGF-I binding in a time - and dose-dependent manner. After 48 h of exposure to T₃, an increase in IGF-I binding was seen with 10^?11M T₃, maximizing with 10^?8M T₃. When cells were exposed to 10^?8 T₃, [¹²⁵I]IGF-I binding reached a maximum of 218 ± 20.8% of control (±SEM, P < 0.002) after 72 h of incubation. Scatchard analysis indicated that T₃ did not alter the K_d of IGF-I for its receptor, but that the total receptor number was increased. Dexamethasone (10^?7M) inhibited the T₃-induced increase in IGF-I binding, but glucocorticoid alone did not substantially alter receptor number. No significant change in insulin or IGF-II binding was seen after hormone treatment. 10^?8 M T₃ or IGF-I increased the growth of the GH₃ cells by ≥30%. Our data indicate that T₃ upregulates IGF-I binding in GH₃ cells without altering insulin binding and thereby provides a means for enhancing potential autocrine regulation in this cell line.