The Inability of Bromocriptine to Inhibit Prolactin Secretion by Transplantable Rat Pituitary Tumors: Observations on the Mechanism and Dynamics of the Autofeedback Regulation of Prolactin Secretion*

Abstract

The effect of several ergot alkaloids on the growth of transplantable rat PRL- and GH-secreting tumors MtTW15 and 7315α was measured. In vivo administration of ergotamine and ergocryptine caused a significant decrease in tumor growth and decreased the serum PRL concentration. Tumor regression was not blocked by the concomitant administration of haloperidol, a dopamine antagonist. The administration of bromocriptine (0.8-40 mg/kg daily) did not cause tumor regression nor did it suppress the elevated serum PRL levels. Since ergotamine and ergocryptine but not bromocriptine are potent vasoconstrictor agents, it is suggested that the former ergot derivatives decrease the capillary blood supply to the tumors and thereby decrease tumor growth and PRL secretion. High serum PRL concentrations are known to produce atrophy of the hosts' pituitary gland and to decrease its synthesis and release of PRL. Since ergotamine significantly decreased the PRL secretion by the tumor, less of a tonic inhibitory signal was presumably perceived by the hypothalamo-pituitary axis, causing the synthesis of PRL by the pituitary gland to increase. Injection of ergocryptine and bromocriptine directly inhibited PRL secretion by the pituitary gland. Ergocryptine and the smaller doses of bromocriptine (0.8 and 2.0 mg/kg daily), although inhibitory to the secretion of PRL, permitted the continued synthesis of the hormone, and thus the pituitary gland content of PRL was increased. The larger doses of bromocriptine (4 and 40 mg/kg daily) inhibited PRL synthesis by the pituitary gland. Rats bearing PRL-secreting pituitary tumors were injected with reserpine (2.0 mg/kg daily for 2 days). Despite the exceedingly high concentration of PRL, injection of reserpine significantly increased the synthesis and release of PRL by the suppressed pituitary gland. These data are consistent with the hypothesis that hypothalamic catecholamines are responsible for the suppression of PRL secetion by the pituitary, and that their depletion restores PRL production by the gland despite an elevated serum PRL concentration.