ACTIONS AND INTERACTIONS OF GROWTH-HORMONE AND INSULIN-LIKE GROWTH FACTOR-II - BODY AND ORGAN GROWTH OF TRANSGENIC MICE

To characterize long-term actions and interactions of growth hormone ( GH) and insulin-like growth factor-II (IGF-II) on postnatal body and o rgan growth, hemizygous phosphoenolpyruvate carboxykinase (PEPCK)-huma n IGF-II transgenic mice were crossed with hemizygous PEPCK-bovine GH transgenic mice. The latter are characterized by two-fold increased se rum levels of IGF-I and exhibit markedly increased body, skeletal and organ growth. Four different genetic groups were obtained: mice harbou ring the IGF-II transgene (I), the bGH transgene (B), or both transgen es (IB), and non-transgenic controls (C). These groups of mice have pr eviously been studied for circulating IGF-I levels (Wolf et al., 1995a ), whereas the present study deals with body and organ growth. Growth curves (week 3 to 12) were estimated by regression with linear and qua dratic components of age on body weight and exhibited significantly (p < 0.001) greater linear coefficients in B and IB than in I and C mice . The linear coefficients of male I and C mice were significantly (p < 0.001) greater than those of their female counterparts, whereas this sex-related difference was absent in the bGH transgenic groups. The we ights of internal organs as well as the weights of abdominal fat, skin and carcass were recorded from 3.5- to 8-month-old mice. In addition, organ weight-to-body weight-ratios (relative organ weights) were calc ulated. Except for the weight of abdominal fat, absolute organ weights were as a rule significantly greater in B and IB than in I and C mice . IGF-II overproduction as a tendency increased the weights of kidneys , adrenal glands, pancreas and uterus both in the absence and presence of the bGH transgene. Analysis of relative organ weights demonstrated significant (p < 0.05) effects of elevated IGF-II on the relative gro wth of kidneys (males and females) and adrenal glands (females), confi rming our previous report on organ growth of PEPCK-ICF-II transgenic m ice. In females, IGF-II and GH overproduction were additive in stimula ting the growth of spleen and uterus, providing evidence for tissue-sp ecific postnatal growth promoting effects by IGF-II in the presence of elevated IGF-I.