GROWTH-HORMONE UP-REGULATES GASTRIN AND PEPTIDE YY GENE-EXPRESSION

The purpose of these studies was to examine the effects of excess grow th hormone (GH) on gastrin and peptide YY (PYY) gene expression. Trans genic mice with the bovine GH gene linked to a mouse metallothionein I promoter were used as a model of chronic GH excess. Antral gastrin mR NA and peptide levels were elevated significantly (P < 0.05) in GH tra nsgenic mice compared with wild type littermates. Ileal PYY mRNA and i leal and colonic PYY levels were significantly elevated in GH transgen ic mice compared with wild type litter mates. The elevations in gastri n and PYY gene expression in GH transgenic mice were independent of fo od intake. Serum concentrations of gastrin and PYY were also elevated in GH transgenic mice. Immunohistochemical analysis showed that the de nsity of PYY-containing cells in the colon of GH transgenic mice and w ild type littermates did not differ. In addition, the mRNA and protein levels of chromogranin A, a marker of endocrine cells, were not incre ased in the colon of GH transgenic mice. Together, these data indicate that GH, insulin-like growth factor I, or both can upregulate gastroi ntestinal gastrin and PYY gene expression directly.