Dopamine as a Prolactin (PRL) Inhibitor

Abstract

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.

Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers

“…As noted earlier, tuberoinfundibular dopaminergic neurons (TIDA) play a predominant role in control of PRL release (Ben-Jonathan, 1985;Ben-Jonathan and Hnasko, 2001). Continuous release of dopamine (DA) is ensured by its high rate of synthesis via hydroxylation of tyrosine to DOPA.…”

“…Opioid peptides of all three classes (mu-, kappa-and delta-) are known to interact with dopaminergic systems within median eminence. A number of neural systems and estradiol (E) (Ben-Jonathan and Hnasko, 2001) are thought to be involved in opioid-mediated hormone release, including noradrenergic (Carr and Gregg, 1995), cholinergic (Kaur, 2001), GABAergic (Kaur, 2001), serotonergic (Foresta et al, 1986), and dopaminergic systems Schlussman et al, 2002).…”

“…The most likely mechanism for the effects of opioids on hormone release relates to TIDA, which consists of neurons with cell bodies in the arcuate and periventricular nuclei of the hypothalamus and axons that project into the median eminence of the hypothalamus. Dopamine released from these axons inhibit prolactin release by binding to dopamine D2 receptors located on pituitary lactotrophs (Ben-Jonathan, 1985;Ben-Jonathan and Hnasko, 2001;Yen and Jaffe, 1999). Thus, a decrease in dopamine levels would lead to increased PRL release.…”

“…PRL is under inhibitory control by dopamine and dopamine antagonists stimulate PRL release (Ben-Jonathan and Hnasko, 2001). This study was part of a series designed to evaluate the effects of nalbuphine on the abuse-related effects of cocaine (Mello et al, 2005).…”

Distribution, Elimination, and Rearrangement of Cyclic Volatile Methylsiloxanes in Oil-Contaminated Soil of the Shengli Oilfield, China

“…This raises the possibility that in utero exposure to D5 could result in adverse effects on brain neural development. Dopamine D2 receptors, with which D5 interacts, have a role in neurological disorders and mental illness (Ben-Jonathan and Hnasko, 2001;Seeman et al, 2006). For example, administration of the dopamine agonist bromocriptine may exacerbate schizophrenia (Ben-Jonathan and Hnasko, 2001) or it may produce improvements in negative symptoms (Lindenmayer, 1995).…”