Dopamine agonists both stimulate and inhibit prolactin release in GH4ZR7 cells.

Prolactin secretion from the anterior pituitary gland is regulated by multiple factors including prolactin-release inhibiting factors (PIFs) and prolactin releasing factors. PIFs, however, usually dominate to exert a tonic inhibition in the biological system, and the physiological PIF is believed to be dopamine. However, there is accumulating evidence that dopamine can not only inhibit but also stimulate prolactin release. Many investigators believe that this is achieved by activating inhibitory and stimulatory subtypes of dopamine receptors. We tried to demonstrate that one subtype of dopamine receptors is capable of both inhibiting or stimulating prolactin release using GH4ZR7 cells. GH4ZR7 cells express only a short form of dopamine D2 receptors (D2s). Low concentrations of three well-established D2 receptor agonists (dopamine, apomorphine and bromocriptine) stimulated prolactin release from GH4ZR7 cells while high concentrations inhibited the release. Haloperidol, a D2 receptor antagonist, blocked the inhibitory action, but was unable to block the dopamine-induced stimulatory action. Pretreatment of cells with phenoxybenzamine, a receptor alkylating agent, abolished both the dopamine-induced stimulatory and inhibitory actions. Our results support the thesis that the stimulation of prolactin release induced by dopamine is mediated through dopamine D2s receptors since the GH4ZR7 cells have only D2s receptors among dopamine receptors. We have concluded that the D2s receptor is capable of both stimulating and inhibiting prolactin release, probably via the activation of a Gs protein by low concentrations and a Gi protein by high concentrations of dopaminergic agents.