GROWTH HORMONE-BINDING PROTEIN IN NORMAL MICE AND IN TRANSGENIC MICE EXPRESSING BOVINE GROWTH-HORMONE GENE

The levels and charactistics of growth hormone (GH)-binding protein (G HBP) and the distribution of GH in peripheral circulation between the free and the bound fractions were studied in three lines of transgenic mice with various degrees of overexpression of bovine (b) GH gene. Tw o serum fractions bound GH specifically: one with low affinity and hig h capacity (GHBP(I)) and one with high affinity and low capacity (GHBP (II)). The GHBP binding capacity in normal mice (both sexes), transgen ic male mice that express the metallothionein-I-hybrid bGH genes, tran sgenic female mice that express phosphoenolpyruvate carboxykinase (PEP CK)- bGH hybrid genes (PEPCK-bGH-1), and transgenic PEPCK-bGH-5 animal s was 1.1 +/- 0.2, 2.0 +/- 0.1, 3.0 +/- 0.1, and 3.9 +/- 0.6 pmol/ml s erum, respectively. The amount of GH bound to GHBP in transgenic anima ls vs. normal siblings was increased 1.8-, 2.5-, and 3.9-fold in these three lines. Consequently, the levels of GH-GHBP complexes in the cir culation of PEPCK-bGH-1 transgenic mice were increased similar to 10-f old. Specific GHBP radioimmunoassay confirmed a threefold increase in GHBP in PEPCK-bGH-1 transgenic animals. The levels of GHBP were not si gnificantly correlated to serum GH within or between lines, perhaps du e to elevation of serum GH in PEPCK-bGH mice above the level producing maximal response. From these and previous studies, we conclude that l ife-long exposure to supranormal GH levels leads to major shifts in GH binding in the circulation and in the GH target organs.