SPECIFIC SOMATOTROPIC AND LACTOGENIC UPTAKE IN-VIVO IN THE LIVERS OF TRANSGENIC MICE EXPRESSING BOVINE GROWTH-HORMONE GENE

The distribution of labeled hGH, oGH and mPRL in different tissues of MT-bGH transgenic and normal mice was investigated using an in vivo te chnique. This technique allows comparisons of tissue uptake of radioac tivity after the labeled hormone was injected alone (20 ng/50 g BW) or together with an excess (300 mug/50 g BW) of unlabeled hormone. Liver , kidney and spleen are the organs that concentrate a significant amou nt of radioactivity 20 min after the injection of labeled hormones, bu t the uptake of radioactivity decreased in the presence of unlabeled h ormones only in the liver. Graphical analysis showed that the disappea rance curves were described by the sum of 3 compartments alpha, beta a nd gamma. The first two are similar in transgenic and in normal mice b ut the third had a t1/2 of 56 +/- 9 min in transgenic and 71 +/- 8 min in normal mice. The inhibition of liver uptake was related to the dos e of unlabeled hormone injected and a half maximal displacement was ob tained with 4 mug and 10 mug of hGH per 50 g of body weight for normal and transgenic mice, respectively. The I-125-hGH taken up in vivo by the liver of transgenic mice was bound to a molecular species with Sto kes radius of approximately 64 angstrom (which is consistent with the molecular size reported for the hormone-receptor complex). Both normal and transgenic mice injected with I-125-hGH showed the presence of tw o types of binding sites for the labelled hormone, since the maximum i nhibition of liver uptake of I-125-hGH was obtained when hGH was injec ted together with the unlabeled hormone, while partial displacements w ere observed with bGH. The liver uptake of radioactivity for both grou ps of mice was higher when I-125-hGH (hormone with lactogenic and soma totropic activities) was administered instead of I-125-oGH (somatotrop ic activity) or I-125-mPRL (lactogenic activity). These results sugges t induction of similar numbers of lactogenic and somatotropic receptor s in the liver of transgenic mice expressing bGH gene.