Prolactin (PRL)-releasing peptide stimulates PRL secretion from human fetal pituitary cultures and growth hormone release from cultured pituitary adenomas

The hypothalamic peptide PRL-releasing peptide (PrRP) has recently been clo ned and identified as a ligand of an orphan pituitary receptor that stimula tes in vitro PRL secretion. PrRP also induces PRL release in rats in vivo, especially in normal cycling females. However, no information on the effect s of PrRP in the human is available. To elucidate the role of PrRP in regul ating human anterior pituitary hormones, we used human PrRP-31 in primary c ultures of human pituitary tissues, including fetal (20-27 weeks gestation) and normal adult pituitaries, as well as PRL- and GH-secreting adenomas. P rRP increased PRL secretion from human fetal pituitary cultures in a dose-d ependent manner by up to 35% (maximal effect achieved with 10 nM), whereas TRH was slightly more potent for PRL release. Coincubation with estradiol r esulted in enhanced fetal PRL response to PrRP, and GH release was only inc reased in the presence of estradiol. Although PRL, secretion from PRL-cell adenomas was not affected by PrRP, PrRP induced PRL release from cultures o f a GH-cell adenoma that cosecreted PRL. PrRP enhanced GH release in severa l GH-secreting adenomas studied by 25-27%, including GH stimulation in a mi xed PRL-GH-cell tumor. These results show for the first time direct in, vit ro effects of PrRP-31 on human pituitary cells. PrRP is less potent than TR H in releasing PRL from human fetal lactohrophs and is unable to release PR L from PRL-cell adenomas in culture, but stimulated GH from several somatot roph adenomas. Thus, PrRP may participate in regulating GH, in addition to PRL, in the human pituitary.