Pituitary control of growth in the neonatal rat: effects of neonatal hypophysectomy on somatic and organ growth, serum insulin-like growth factors (IGF)-I and -II levels, and expression of IGF binding proteins

Abstract

The neonatal period is a time of transition between pituitary-independent fetal growth and the pituitary-dependent growth seen in older mammals. To evaluate pituitary-dependent neonatal growth, Wistar rats were hypophysectomized (Hx) on postnatal day 6. Nineteen days post-Hx, body weight and tail length were inhibited 48% and 34%, respectively, compared with sham-Hx controls. Organ weights determined on days 10, 15, 20, 25, and 30 revealed three patterns of pituitary-dependence: 1) pituitary-independent growth in the brain and lung; 2) moderate pituitary-dependent growth in the heart, liver, kidney, and intestine; and 3) marked pituitary-dependent growth in the adrenals, spleen, and testes. Both serum insulin-like growth factor (IGF)-I and -II levels fell significantly in Hx pups by 54 h after Hx (P = 0.0005), and Northern analysis on day 15 showed a significant decrease in liver messenger RNA (mRNA) for IGF-II. Analysis of the major IGF binding proteins (BPs) was performed by Western ligand blots. Hx performed on day 6 resulted in a linear decrease in the amount of the 22k BP from day 10 to day 30. In contrast, the major neonatal BP (IGFBP-2, a 29.5k molecule) showed a biphasic response to neonatal Hx. On postnatal day 10, 4 days after Hx, a significant decrease in IGFBP-2 occurred, which persisted through day 15; by postnatal day 20 and continuing through postnatal day 30, the amount of IGFBP-2 in the serum dramatically increased. The 40 to 50k fraction of IGFBP-3 first appeared in significant quantities by postnatal day 20, and after Hx dropped to 10% of sham-control values. Similarly, Northern analysis on day 15 demonstrated a significant decrease in liver, but not brain, mRNA for IGFBP-2 after Hx, whereas on postnatal day 25, liver mRNA for IGFBP-2 was increased in Hx pups compared with sham controls. We conclude that the pituitary gland exerts significant but selective effects on neonatal growth, with the notable exception of brain growth. Serum levels of both IGF-I and IGF-II, as well as their BPs, are pituitary dependent in the neonatal period. Pituitary-dependent neonatal growth thus appears to be mediated by IGF and modulated by IGF-binding proteins. On the other hand, that portion of the persistent growth in the neonatal Hx rat that is independent of the pituitary-IGF axis may be a good model for investigation of fetal growth.