The Inhibition of Phosphatidylinositol Turnover: A Possible Postreceptor Mechanism for the Prolactin Secretion-Inhibiting Effect of Dopamine

We studied the association between the inhibition of phosphatidylinositol (PI) turnover and the inhibition of PRL secretion in the presence of dopamine. The incorporation of radiolabeled phosphate into anterior pituitary gland PI as well as serum PRL levels were significantly (P < 0.01) greater in female than in male rats. No significant sex-related difference was found in the incorporation by pituitary tissue of ³²P into phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Dopamine decreased the incorporation of ³²P into PI, but not into PC or PE, by female rat pituitary glands; this effect was reversed by two dopamine receptor-blocking agents, haloperidol and pimozide. After dopamine was removed from the incubation medium, basal ³²P incorporation into PI was restored within 10 min. The administration of bromocriptine (500 μg/kg, ip, 4 h earlier) significantly reduced pituitary PI turnover. Conversely, in vivo injection of 0α-methyl-p-tyrosine (0αMpT; 200 mg, ip, 2.5 h before death), an inhibitor of catecholamine biosynthesis, dramatically increased serum PRL levels. In vitro incorporation of ³²P into PI, but not into PC or PE, increased (+130%) when these glands were incubated for 30 min with radiolabeled phosphate. The in vitro addition of 0.5 μM dopamine to glands from 0αMpT-treated rats counteracted the stimulation of ³²P incorporation into PI produced by 0αMpT treatment. In rats bearing the transplantable PRL-secreting tumor MtTWl5, the hyperprolactinemia produced by the tumor stimulates hypothalamic turnover of dopamine, with a consequent inhibition of pituitary gland PRL secretion. ³²P incorporation into PI, but not into PC or PE, was significantly (P < 0.01) inhibited (–41%) in pituitary glands from these rats. The injection of 0αMpT (200 mg/kg, ip) or haloperidol (2 mg/kg, ip) 12 and 3 h before death into MtTW15 tumor-bearing rats abolished the inhibition of ³²P incorporation into pituitary PI. Dopamine also decreased PI turnover in the 7315a PRL-secreting pituitary tumor. Our data indicate that the PI cycle may be an intracellular mechanism controlling PRL release in the rat and that the changes in its cleavage and turnover may be an early postreceptor event responsible for the inhibition of PRL secretion produced by factors such as dopamine. (Endocrinology 113: 7, 1983).