Tissue distribution and molecular heterogeneity of human growth hormone-releasing factor in the transgenic mouse.

Transgenic mice expressing the human growth hormone-releasing factor (hGRF) gene linked to the metallothionein promoter exhibit high circulating levels of hGRF and GH and increased growth. We have described the distribution of GRF immunoreactivity (GRF-IR) in various tissues and characterized its molecular heterogeneity using gel filtration and high performance liquid chromatography (HPLC) and two separate RIAs that recognized mid-molecule and carboxyl-terminal epitopes of hGRF. The highest levels of GRF-IR were in the pituitary, followed by the pancreas. Intermediate levels were present in hypothalamus and liver, and lower levels in visceral organs, heart, and gonads. The pituitary and brain revealed evidence of the two mature hormone forms [hGRF(l–44)-NH2 and hGRF(l–40)-OH and in addition a more hydrophobic form that is believed to represent the hGRF precursor (proGRF) on the basis of its estimated molecular size (∽9,000) and selective recognition by the mid-molecule RIA. The profiles of GRF in pancreas...