GALANIN REGULATES PROLACTIN-RELEASE AND LACTOTROPH PROLIFERATION

The neuropeptide galanin is predominantly expressed by the lactotrophs (the prolactin secreting cell type) in the rodent anterior pituitary and in the median eminence and paraventricular nucleus of the hypothal amus. Prolactin and galanin colocalize in the same secretory granule, the expression of both proteins is extremely sensitive to the estrogen status of the animal, The administration of estradiol-17 beta induces pituitary hyperplasia followed by adenoma formation and causes a 3,00 0-fold increase in the galanin mRNA content of the lactotroph. To furt her study the role of galanin in prolactin release and lactotroph grow th we now report the generation of mice carrying a loss-of function mu tation of the endogenous galanin gene. There is no evidence of embryon ic lethality and the mutant mice grow normally. The specific endocrine abnormalities identified to date, relate to the expression of prolact in, Pituitary prolactin message levels and protein content of adult fe male mutant mice are reduced by 30-40% compared with wild-type control s. Mutant females fail to lactate and pups die of starvation/dehydrati on unless fostered onto wild-type mothers. Prolactin secretion in muta nt females is markedly reduced at 7 days postpartum compared with wild -type controls with an associated failure in mammary gland maturation. There is an almost complete abrogation of the proliferative response of the lactotroph to high doses of estrogen, with a failure to up-regu late prolactin release, STAT5 expression or to increase pituitary cell number. These data further support the hypothesis that galanin acts a s a paracrine regulator of prolactin expression and as a growth factor to the lactotroph.