Galanin is a peptide widely distributed throughout vertebrate central and peripheral nervous systems. Although its precise physiologic role is unknown, it can stimulate the pituitary secretion of prolactin and growth hormone. We examined the control of rat galanin (rGal) gene expression in the anterior pituitary using RNA blot and in situ hybridization analyses and using specific RIA. Pituitaries of normal male and ovariectomized female rats contained little detectable rGal mRNA. Treatment of these animals with 17fi-estradiol increased pituitary rGal mRNA up to 4000-fold.These increases depended on time and dose of estrogen administration and correlated with up to 50-fold increases in pituitary galanin-like immunoreactivity. Galanin-like immunoreactivity was detectable in the plasma of estrogen-treated animals. Pituitary levels of rGal mRNA in female rats varied >30-fold during the estrous cycle, with a peak on estrus and a nadir on diestrus. Estrogen-induced rGal gene expression was also observed in transplantable MtTW1s prolactin-and growth hormone-containing tumors but not in neuronal tissues expressing this gene. These data demonstrate that rGal is a secreted product of rat anterior pituitary cells, where its gene expression is strongly affected by physiologic levels of circulating estrogen.Galanin is a 29-amino acid peptide, initially isolated from porcine intestine, that has little similarity to other known peptides (1). Galanin-like immunoreactivity (Gal-IR) is widely distributed in central and peripheral neurons of several mammalian species including humans, nonhuman primates, dogs, cats, cows, and various rodents (2). In addition, Gal-IR has been detected in bovine and porcine adrenal medulla (2, 3). Its intracellular localization suggests that galanin may function as a neurotransmitter. Moreover, a 53-to 55-kDa peptide has been isolated from the cell membrane fraction of rat brain and a hamster pancreatic beta cell tumor that selectively binds radiolabeled galanin with high affinity, consistent with a role as a galanin receptor protein (4,5).Although the precise physiologic role of galanin has not been established, the peptide has been shown to have several pharmacologic properties in whole animal and isolated tissue preparations. Direct injection of porcine galanin (pGal) into the third ventricle of rats increases plasma concentrations of growth hormone (GH) and prolactin and decreases dopamine concentrations in the median eminence (6-9). Intravenous pGal injection in humans stimulates GH release and augments the GH release induced by exogenous GH-releasing hormone (10, 11). pGal has little stimulatory effect on the release of these hormones in isolated pituitary preparations (6,(12)(13)(14), and there is evidence that its effects are exerted indirectly via the release of dopamine (for prolactin) and somatostatin (for GH) (8,11,15). Intracerebroventricular pGal increases luteinizing hormone release in ovariectomized rats treated with exogenous estrogen and progesterone (16). Intravenous pGal i...