REGULATION OF ANTERIOR-PITUITARY GALANIN AND VASOACTIVE-INTESTINAL-PEPTIDE BY ESTROGEN AND PROLACTIN STATUS

The neuropeptides vasoactive intestinal peptide (VIP) and galanin are synthesized in the anterior pituitary, galanin in the lactotroph and V IP probably in another cell type, and both stimulate prolactin secreti on. Oestrogen regulates anterior pituitary VIP and galanin, galanin ex pression reflecting physiological variation in oestrogen status, whils t VIP is induced by pharmacological concentrations of oestrogen. Impla nting anterior pituitaries under the renal capsule to induce hyperprol actinaemia we studied the regulation of anterior pituitary VIP and gal anin synthesis and storage by prolactin and its interaction with oestr ogen status. Five groups of animals were studied: control, hypophysect omized implanted, implanted, hyperoestrogenized (oestradiol-17 beta; 2 50 mu g/day) and hyperoestrogenized implanted. Spontaneously cycling a nimals were followed through two cycles prior to implanting and were m aintained for at least 1 week and then killed once they were in dioest rus. Circulating prolactin levels were significantly elevated in impla nted animals but not in hypophysectomized implanted animals compared w ith controls. There was a more marked increase in prolactin levels in hyperoestrogenized animals and hyperoestrogenized implanted animals, w ith no significant difference between these two groups. Native anterio r pituitary galanin and VIP content was suppressed in implanted animal s, and markedly increased in hyperoestrogenized animals. Pituitary imp lantation only marginally reduced the effect of hyperoestrogenization on galanin content but abolished the effect of hyperoestrogenization o n VIP content. Implant peptide content was suppressed to less than 10% of native anterior pituitary content. Galanin was not detected in imp lants from hypophysectomized-implanted animals but implant VIP content was unaffected by hypophysectomy. VIP content was increased in implan ts from hyperoestrogenized implanted animals but implant galanin conte nt was unaffected by hyperoestrogenization. Peptide mRNA levels change d in parallel with peptide content except that the implant galanin mRN A levels were increased by hyperoestrogenization. Thus it appears that prolactin negatively regulates anterior pituitary galanin and VIP gen e expression and content, probably due to a direct effect on the anter ior pituitary and by altered secretion of hypothalamic factors. Oestro gen is a potent stimulus to expression of both peptide genes. Its posi tive effect on anterior pituitary peptide gene expression and content is greatly diminished by the effect of implant-induced hyperprolactina emia, suggesting that circulating prolactin levels may be controlled b y a negative feedback effect of prolactin on galanin and VIP. A simila r effect of hyperoestrogenization is observed in the implants, except that galanin content remains at a low level, suggesting that the combi nation of hyperoestrogenization and the absence of dopamine may lead t o uncontrolled release of high levels of galanin.