Dopamine as a prolactin (PRL) inhibitor.
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.
Ben-Jonathan
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Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati Medical Center, Cincinnati, Ohio 45267, USA. Nira.Ben-Jonathan@uc.edu
Hnasko
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D000818:Animals; D004298:Dopamine / Q000502:physiology*; D005260:Female; D006801:Humans; D007031:Hypothalamus / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D010902:Pituitary Gland / Q000502:physiology; D011247:Pregnancy; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000502:physiology; D011954:Receptors, Dopamine; D011981:Receptors, Prolactin
D011954:Receptors, Dopamine; D011981:Receptors, Prolactin; D011388:Prolactin; D004298:Dopamine