Ontogeny of Pituitary Regulation of Growth in the Developing Rat: Comparison of Effects of Hypophysectomy and Hormone Replacement on Somatic and Organ Growth, Serum Insulin-Like Growth Factor-I (IGF-I) and IGF-II Levels, and IGF-Binding Protein Levels in the Neonatal and Juvenile Rat*

Abstract

We investigated pituitary regulation of growth during two critical stages of development in the rat, using hypophysectomy (Hx) with replacement of GH and/or T4. In the neonatal period (Hx on day 6), body weight and tail length were inhibited by 60% and 50%, respectively, while these parameters were inhibited by 80% and 85% by Hx in the juvenile period (Hx on day 45). Administration of T4 alone significantly increased skeletal growth (tail length) in neonatal Hx rats, while T4 alone proved ineffective in promoting somatic growth in juvenile Hx rats. GH effects were greater on body weight than on tail length at both stages of development. Replacement of both GH and T4 restored somatic growth to normal values during both time periods. The brain was the sole organ whose growth appeared to be independent of the pituitary. Hx reduced serum insulin-like growth factor-I (IGF-I) and -II in both age groups, and GH alone restored IGF-I and -II levels to the control range. The major IGF-binding proteins (IGFBPs) were analyzed by Western ligand blots. The effect of Hx on the predominant IGFBP was greater in the juvenile rat. T4 replacement in the neonate and GH replacement in the juvenile rat restored IGFBPs to control levels. We conclude that somatic growth in the rat is less pituitary dependent in the neonatal period. There are also important age-specific differences in organ response to GH and T4. Serum IGFs and their binding proteins are pituitary dependent even in infancy, and GH is their primary regulator. The neonatal Hx rat is an important model for the study of the dynamic development of the pituitary-dependent growth.