THE EFFECTS OF THYROXINE ON SERUM AND TISSUE CONCENTRATIONS OF INSULIN-LIKE GROWTH-FACTORS (IGF-I AND IGF-II) AND IGF-BINDING PROTEINS IN THE FETAL PIG

We have extensively studied the effect of hypophysectomy on the growth and development of tissues in the fetal pig. However, little is known about the effect of hypophysectomy on tissue levels of insulin-like g rowth factors I and II (IGF-I and -II) and how these growth factors ar e affected by T4 replacement. Fetal pigs were hypophysectomized (Hypox ) at 70 days of gestation, and pellets containing 15 mg T4 were implan ted into the lateral musculature of the hind limb at either 70 or 90 d ays of gestation. Fetuses were removed at either 90 or 105 days of ges tation, respectively. Control (non-Hypox), Hypox, and T4 (Hypox-T4) fe tal weights were similar at 90 days, but Hypox-T4 weighed less than co ntrol and Hypox fetuses at 105 days. Hypophysectomy decreased levels o f serum T4, LH, cortisol, and IGF-I (105 days) when compared with cont rols. Heart and liver (105 days and 90 days) and fat, muscle, and kidn ey (90 days) IGF-I levels were lower in Hypox fetuses when compared wi th controls. Hypophysectomy decreased concentrations of IGF-II in only 105-day fetal kidneys. Hypophysectomy decreased serum levels of IGF b inding protein 1 (IGFBP-1) (90 days) and IGFBP-2 (105 days) and increa sed IGFBP-4 (105 days) in comparison with control. T4 treatment of Hyp ox fetuses increased serum concentrations of T4 and IGF-I over Hypox l evels at both 90 and 105 days gestation. Cortisol levels remained decr eased in the T4-treated fetuses. Levels of IGF-I in the heart (90 and 105 days) and liver (90 days) of Hypox fetuses were increased by T4 tr eatment. T4 did not effect tissue IGF-II levels when compared with Hyp ox. T4 increased serum IGFBP-1, -2, and -4 levels over Hypox values. W e suggest that T4 enhances production of IGF-I (as opposed to IGF-II), which in turn mediates some of T4's capability to enhance tissue deve lopment in the fetal pig.