DOPAMINERGIC REGULATION OF GALANIN GENE-EXPRESSION IN THE RAT ANTERIOR-PITUITARY GLAND

Estrogen dramatically increases galanin mRNA and peptide levels in the rat anterior pituitary gland. We recently reported that galanin secretion in vitro from estrogen-exposed anterior pituitary cells is regulated by hypothalamic factors; dopamine and somatostatin inhibit galanin secretion, and thyrotrophin-releasing hormone stimulates galanin release. To determine whether galanin is regulated by a dopaminergic mechanism in vivo, we used ovariectomized Fischer 344 rats treated with 17-beta-estradiol-containing or empty Silastic capsules. Rats were also administered bromocriptine, a dopamine receptor agonist, haloperidol, a dopamine receptor antagonist, or placebo for 2 weeks. Galanin peptide levels were measured in the anterior pituitary, neurointermediate lobe, medial basal hypothalamus, and plasma by radioimmunoassay. Plasma and pituitary prolactin levels were also determined. Bromocriptine decreased galanin peptide levels in the anterior pituitary gland of ovariectomized rats by 30%, but had no effect on galanin in the neurointermediate lobe or medial basal hypothalamus. In contrast, haloperidol had no effect on galanin in the anterior pituitary or medial basal hypothalamus of ovariectomized rats, but decreased galanin peptide levels in the neurointermediate lobe. In the anterior pituitary gland of estrogen-treated rats, bromocriptine increased and haloperidol decreased both galanin and prolactin levels. Galanin mRNA levels were quantified in the anterior pituitary gland by solution hybridization. Bromocriptine increased galanin mRNA levels 3-fold in the anterior pituitary, whereas haloperidol had no effect. Galanin mRNA levels in the anterior pituitary were elevated 10-fold by estrogen. Bromocriptine reduced galanin mRNA levels in the pituitary by 50% in estrogen-treated rats, where again haloperidol had no effect. Estrogen increased plasma galanin levels 4-fold compared to ovariectomized rats and this effect was reduced 60% by bromocriptine and increased 20% by haloperidol. We conclude 1) galanin synthesis and release from the estrogen-exposed anterior pituitary gland is inhibited by a dopaminergic mechanism in vivo, 2) dopamine regulates galanin gene expression in the ovariectomized rat, 3) the changes in galanin peptide levels in the anterior pituitary of rats treated with estrogen and dopamine receptor ligands are primarily due to alterations in peptide secretion, and 4) galanin release from the neurointermediate lobe may also be regulated by a dopaminergic mechanism in vivo. These data, in conjunction with previous studies, provide evidence for the co-regulation of galanin and prolactin in estrogen-treated rats, and further discriminate between the regulation of galanin in the hypothalamus and pituitary gland.