Effects of cyproheptadine on prolactin synthesis and release by normal and suppressed pituitary glands and by dispersed pituitary tumor cells.

Abstract

Trypsin-dispersed cells obtained from the transplantable PRL-secreting rat pituitary tumor MtTWl5 and normal whole pituitary glands were used to study the mechanism of action of cyproheptadine on the secretion of radioimmunoassayable and newly synthesized [3H]PRL. Cyproheptadine inhibited basal PRL release, whereas dibutyryl cAMP stimulated the in vitro secretion of PRL by these cells. The increase in PRL secretion was blocked by coincubation of the cells with cyproheptadine. No effect of cyproheptadine was observed on the synthesis and release of GH by the pituitary glands. Since serotonin was previously shown to have no direct effect on PRL secretion by the pituitary gland in vitro, the inhibiting effect of cyproheptadine on PRL secretion is probably not mediated by a specific antagonistic action on serotonin receptors on the pituitary lactotroph. The cyproheptadine-mediated inhibition of PRL secretion is also not mediated by activation of the dopamine receptor, because the effect of the drug was not bl...