Dopamine is a small and relatively simple molecule that fulfills diverse functions. Within the brain, it acts as a classical
neurotransmitter whose attenuation or overactivity can result in disorders such as
Parkinson's disease and
schizophrenia. Major advances in the cloning and characterization of biosynthetic
enzymes, transporters, and receptors have increased our knowledge regarding the metabolism, release, reuptake, and mechanism of action of
dopamine.
Dopamine reaches the pituitary via hypophysial portal blood from several hypothalamic nerve tracts that are regulated by PRL itself,
estrogens, and several
neuropeptides and
neurotransmitters.
Dopamine binds to type-2
dopamine receptors that are functionally linked to
membrane channels and
G proteins and suppresses the high intrinsic secretory activity of the pituitary lactotrophs. In addition to inhibiting PRL release by controlling
calcium fluxes,
dopamine activates several interacting intracellular signaling pathways and suppresses PRL gene expression and lactotroph proliferation. Thus, PRL homeostasis should be viewed in the context of a fine balance between the action of
dopamine as an inhibitor and the many hypothalamic, systemic, and local factors acting as stimulators, none of which has yet emerged as a primary PRL releasing factor. The generation of transgenic animals with overexpressed or mutated genes expanded our understanding of
dopamine-PRL interactions and the physiological consequences of their perturbations. PRL release in humans, which differs in many respects from that in laboratory animals, is affected by several drugs used in clinical practice.
Hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in both men and women. The treatment of
hyperprolactinemia has greatly benefited from the generation of progressively more effective and selective
dopaminergic drugs.