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.