The 7315a Pituitary Tumor Is Refractory to Dopaminergic Inhibition of Prolactin Release But Contains Dopamine Receptors*

Abstract

The PRL-secreting pituitary tumor 7315a was grown in female rats, tested for its biological responsiveness, and monitored for the presence of dopamine (DA) receptors under in vitro conditions. The basal PRL secretion from enzymatically dispersed tumor cells or fragments not treated with enzyme was 10-30 times less than that from dispersed or fragmented anterior pituitary cells which were continuously perifused in a cell column apparatus. Neither DA, its agonists pergolide and lisuride, nor the DA antagonist metoclopramide in the presence of agonist affected PRL release from the tumor cells. In contrast to these results, the same dopaminergic agonists caused a dramatic inhibition of PRL release from the normal anterior pituitary cells, while coincubation with antagonists reversed the agonist effect. Thus, the tumor was refractory to DA agonist inhibition of PRL release. In contrast, TRH was capable of stimulating PRL secretion from both the tumor and the anterior pituitary cells. The binding of the DA antaonist [³H]spiperone to homogenates of the 7315a tumor was saturable, reversible, and stereoselective. The order of potency of a large variety of agonists and antagonists was characteristic of an interaction at a DA receptor and was highly correlated with the potencies previously reported for the DA receptor of the anterior pituitary. The guanine nucleotide 5′-guanylimide-diphosphate reduced the affinity of the agonists DA, apomorphine, and 6, 7-ADTN by 3–6 times, but had no effect on the affinity of the antagonists haloperidol, d-butaclamol, and l-sulpiride and the agonist bfomocriptine. Although the 7315a pituitary tumor is refractory to DA agonist inhibition of PRL release, it possesses DA receptors; thus, a defect may exist at a postreceptor site in this tumor cell, in contrast to the GH₃ cell line where there is no detectable receptor.