VASOACTIVE INTESTINAL POLYPEPTIDE MESSENGER-RNA AND PEPTIDE LEVELS ARE DECREASED IN THE ANTERIOR-PITUITARY OF THE HUMAN GROWTH HORMONE-RELEASING HORMONE TRANSGENIC MOUSE

We recently reported that galanin gene expression is markedly increase d in the hyperplastic anterior pituitary gland of the human growth hor mone-releasing hormone (hGHRH) transgenic mouse. To determine if anoth er pituitary peptide hormone with putative growth-promoting activity i s similarly affected, or if this effect is specific to the peptide gal anin, we examined vasoactive intestinal polypeptide (VIP) gene express ion in the hypothalamic-pituitary axis of male hGHRH transgenic and no n-transgenic mice. The objectives were to: 1) assess VIP peptide conce ntrations, 2) estimate relative differences in VIP mRNA levels, 3) det ermine the effects of acute treatment with 17 beta-estradiol on VIP pe ptide and mRNA levels, and 4) quantify the density of immunoreactive V IP pituitary cells by immunohistochemistry. Four to five month old mal e hGHRH transgenic mice and their non-transgenic siblings were identif ied by PCR. Immunoreactive VIP concentrations were decreased by 50% in the anterior pituitary glands of hGHRH transgenic mice as compared to non-transgenic siblings. In contrast, no differences in immunoreactiv e VIP concentrations were observed in the hypothalamus or frontal cere bral cortex of transgenic and nontransgenic mice. Treatment with 17 be ta-estradiol significantly increased VIP concentrations in the anterio r pituitary gland of both transgenic and non-transgenic mice; however, VIP peptide concentrations in the anterior pituitary glands of hGHRH transgenic mice remained 50% lower. Relative differences in VIP mRNA l evels were estimated by RT-PCR, and were found to be 2.5-fold higher i n the anterior pituitary glands of non-transgenic mice. In contrast, n o differences in VIP mRNA levels in the cerebral cortex were detected between transgenic and non-transgenic mice. Treatment with 17 beta-est radiol increased VIP mRNA levels in the anterior pituitary, but not in the cerebral cortex, In concert with the changes in VIP peptide and m RNA, the density of immunoreactive VIP pituitary cells was decreased a pproximately 50% in hGHRH transgenic mice. In conclusion, unlike galan in gene expression, VIP peptide and mRNA levels are significantly decr eased in the anterior pituitary gland of hGHRH transgenic mice. Moreov er, these changes appear to be tissue-specific and are likely due, in part, to the decrease in the density of VIP-containing pituitary cells in the hyperplastic pituitary. Although the pituitary cell type(s) sy nthesizing VIP remains unclear, these data suggest that VIP in the ant erior pituitary is not stimulating pituitary tumor development in hGHR H transgenic mice.