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Effects of Cyproheptadine on Prolactin Synthesis and Release by Normal and Suppressed Pituitary Glands and by Dispersed Pituitary Tumor Cells^*

STEVEN W. J. LAMBERTS and ROBERT M. MACLEOD

Department of Medicine, Division of Endocrinology, University of Virginia School of Medicine Charlottesville, Virginia 22901

Address requests for reprints to: Dr. Robert M. MacLeod, Department of Internal Medicine, University of Virginia 22901.

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 blocked by low concentrations of specific dopamine receptor-blocking agents (perphenazine, pimozide, and haloperidol). It is concluded that cyproheptadine inhibits the in vitro synthesis and release of PRL by pituitary cells of normal and neoplastic origin by an unknown nonserotonin-linked mechanism.

Chronic administration of cyproheptadine to rats bearing a transplantable PRL-secreting pituitary tumor, however, had a stimulating effect on the PRL synthesis and release by the suppressed, atrophied pituitary glands of these animals. In addition, methysergide administration also increased the radioimmunoassayable PRL content of the pituitary gland and additionally stimulated the growth of atrophied pituitary gland in tumor-bearing rats.

Footnotes

^* This work was supported by USPHS Research Grants CA-07535-14 and CA-16664-3 from the National Cancer Institute.

On leave from Department of Internal Medicine (III) and Clinical Endocrinology, University Hospital Dijkzigt, Erasmus University, Rotterdam, the Netherlands.

Received January 16, 1978.