Department of Cell Biology, Neurobiology, and Anatomy, University
of Cincinnati Medical Center, Cincinnati, Ohio 45267
Correspondence: Address all correspondence and requests for reprints to: Dr. Nira Ben-Jonathan, Department of Cell Biology, 3125 Eden Avenue, University of Cincinnati, Cincinnati, Ohio 45267-0521. E-mail:
Nira.Ben-Jonathan{at}uc.edu
Dopamine is a small and relatively simple molecule that
fulfillsdiverse functions. Within the brain, it acts as a classical
neurotransmitterwhose attenuation or overactivity can result in
disorders suchas Parkinson’s disease and schizophrenia. Major
advancesin 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.
Dopaminereaches the pituitary via hypophysial portal blood from
severalhypothalamic nerve tracts that are regulated by PRL itself,
estrogens,and several neuropeptides and neurotransmitters. Dopamine
bindsto type-2 dopamine receptors that are functionally linked to
membranechannels and G proteins and suppresses the high intrinsic
secretoryactivity of the pituitary lactotrophs. In addition to
inhibitingPRL release by controlling calcium fluxes, dopamine
activatesseveral interacting intracellular signaling pathways and
suppressesPRL gene expression and lactotroph proliferation. Thus, PRL
homeostasisshould be viewed in the context of a fine balance between
theaction of dopamine as an inhibitor and the many hypothalamic,
systemic,and local factors acting as stimulators, none of which has
yetemerged as a primary PRL releasing factor. The generation of
transgenicanimals with overexpressed or mutated genes expanded our
understandingof dopamine-PRL interactions and the physiological
consequencesof their perturbations. PRL release in humans, which
differsin many respects from that in laboratory animals, is affected
byseveral drugs used in clinical practice. Hyperprolactinemiais a
major neuroendocrine-related cause of reproductive disturbancesin both
men and women. The treatment of hyperprolactinemia hasgreatly
benefited from the generation of progressively moreeffective and
selective dopaminergic drugs.
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