Targeted overexpression of galanin in lactotrophs of transgenic mice induces hyperprolactinemia and pituitary hyperplasia

We generated transgenic mice that carry 4.6 kb of the mouse galanin gene fu sed to 2.5 kb of the rat PRL promoter. In all transgenic lines that carried and transmitted the transgene, there were significant increases in galanin messenger RNA and peptide levels in the anterior pituitary in both male an d female transgenic mice, and the elevation of galanin was restricted to th e anterior lobe. Furthermore, galanin release from pituitary cells in vitro of both male and female transgenic mice was dramatically increased compare d with that in control mice. At 2-4 months of age, pituitary PRL contents i n female transgenic mice were increased compared with those in normal contr ols. Moreover, PRL messenger RNA levels were increased in female transgenic mice. However, plasma levels of PRL in female transgenic mice were not sig nificantly higher until 6 months of age. By 11 months of age, cell numbers in the anterior pituitary were increased in female, but not male, transgeni c mice. The percentage of lactotrophs in female transgenic mice as well as PRL gene expression per cell were significantly higher. No differences were detected in PRL content, gene expression, or release between normal and tr ansgenic male mice. Six weeks of estrogen treatment significantly increased anterior pituitary weights and PRL secretion in male transgenic mice compa red with that in normal male mice. In addition, anterior pituitary weights and PRL secretion were decreased in female transgenic mice compared with co ntrols 6 weeks after ovariectomy. We conclude that overexpression of galani n in lactotrophs stimulates PRL synthesis and secretion and acts as a growt h factor resulting in the formation of pituitary hyperplasia and hyperprola ctinemia. Furthermore, estrogen appears critical for these galanin-mediated events.