GALANIN GENE-EXPRESSION IS INCREASED IN THE ANTERIOR-PITUITARY GLAND OF THE HUMAN GROWTH HORMONE-RELEASING HORMONE TRANSGENIC MOUSE

The peptide galanin is synthesized within and secreted from specific c ells of the anterior pituitary gland. Previous studies showed that GH- releasing hormone (GHRH) stimulates galanin release from pituitary cel ls in vitro. In the present study we used human (h) GHRH transgenic mi ce to examine the effects of high circulating levels of GHRH on pituit ary galanin gene expression in vivo. Moreover, the hGHRH transgenic mi ce develop pituitary tumors and, thus, may be used as a model of estro gen-independent pituitary adenoma formation. We examined male hGHRH tr ansgenic mice and nontransgenic siblings at 2, 4, 6, 8, and 10 months of age. Transgenic mice were identified using the polymerase chain rea ction. Body weights and plasma mGH levels were higher in transgenic mi ce at all ages. Total protein contents in the anterior pituitary gland s of transgenic mice were significantly greater at each age. Galanin p eptide contents in the anterior pituitary gland of hGHRH mice were nor malized for differences in total protein content and were significantl y elevated at all ages examined. At 10 months of age, anterior pituita ry galanin peptide concentrations were increased 7-fold. Hypothalamic concentrations of galanin peptide were also increased in hGHRH transge nic mice, but were not greater than those in nontransgenic siblings un til 4 months of age. In contrast, no significant differences in galani n peptide concentrations of the neurointermediate lobes were evident. Galanin mRNA concentrations in the anterior pituitary of 6-month-old t ransgenic mice were increased 4-fold. In conclusion, 1) galanin peptid e concentrations in the anterior pituitary gland and hypothalamus are increased in hGHRH transgenic mice compared to those in nontransgenic siblings, whereas galanin peptide concentrations in the neurointermedi ate lobe are not different; 2) pituitary galanin mRNA concentrations a re increased 4-fold in 6-month-old transgenic mice; and 3) the develop ment of pituitary hyperplasia is correlated to the increase in galanin mRNA and peptide concentrations.