Expression of human growth hormone-releasing factor in transgenic mice results in increased somatic growth

作者: Robert E. Hammer , Ralph L. Brinster , Michael G. Rosenfeld , Ronald M. Evans , Kelly E. Mayo

DOI: 10.1038/315413A0

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摘要: The neurohumoral regulation of growth hormone secretion is mediated in part by two hypothalamic peptides that reach the anterior pituitary via hypothalamo-hypophysial portal blood system1. Somatostatin inhibits release hormone2, whereas hormone-releasing factor (GRF) positively regulates both synthesis3,4 and secretion5,6. Two forms human GRF, 40 44 amino acids long, have been characterized from extra-hypothalamic tumours7,8 as well hypothalamus9. Analysis GRF complementary DNA10,11 genomic12 clones indicates are first synthesized a 107- or 108-amino-acid precursor protein. To examine physiological consequences expression, we established strains transgenic mice containing fusion gene including promoter/regulatory region mouse metal-lothionein-I (MT-I) gene13 coding gene12. We report expression protein these animals results measurable levels increased plasma accelerated rates relative to control littermates. These demonstrate direct role for positive somatic growth. Unexpectedly, female carrying MT-GRF fertile, contrast expressing rat hormone, which generally infertile. should provide useful animal models study several types disorders.

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