Abstract Triiodothyronine (T(3)) stimulates the synthesis of growth hormone and enhances the growth of neoplastic rat pituitary somatomam-motrophs (GH cells) in culture. Moreover, T(3) 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 GH(3) 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 T(3) affects IGF-I binding to GH(3) cells. T(3) increased [(125)I]IGF-I binding in a time - and dose-dependent manner. After 48 h of exposure to T(3), an increase in IGF-I binding was seen with 10(-11)M T(3), maximizing with 10(-8)M T(3). When cells were exposed to 10(-8) T(3), [(125)I]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 T(3) did not alter the K(d) of IGF-I for its receptor, but that the total receptor number was increased. Dexamethasone (10(-7)M) inhibited the T(3)-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 T(3) or IGF-I increased the growth of the GH(3) cells by >/=30%. Our data indicate that T(3) upregulates IGF-I binding in GH(3) cells without altering insulin binding and thereby provides a means for enhancing potential autocrine regulation in this cell line.