This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DeMaria, J. E. Articles by Freeman, M. E. Search for Related Content PubMed PubMed Citation Articles by DeMaria, J. E. Articles by Freeman, M. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB COCAINE DOPAMINE ESTRADIOL MAZINDOL

Dopamine Transporters Participate in the Physiological Regulation of Prolactin¹

Department of Biological Science (J.E.D., A.A.L., M.E.F.) and Department of Nutrition, Food, and Exercise Sciences (C.W.L.), Program in Neuroscience, Florida State University, Tallahassee, Florida 32306-4340; Neuroendocrine Research Laboratory (G.M.N.), Department of Human Morphology and Embryology, Semmelweis Medical University, Budapest, Hungary; and Institute of Experimental Medicine (M.I.E.F.), Hungarian Academy of Sciences, Budapest, Hungary

Address all correspondence and requests for reprints to: Marc E. Freeman, Ph.D., 208 Biomedical Research Facility, Florida State University, Tallahassee, Florida 32306-4340. E-mail: freeman{at}neuro.fsu.edu

Three populations of hypothalamic neuroendocrine dopaminergic (NEDA) neurons, arising from the arcuate and periventricular nuclei of the hypothalamus release dopamine (DA) that acts at the pituitary gland to regulate the secretion of PRL. It is generally accepted that NEDA neurons lack functional DA transporters (DATs), which are responsible for uptake of DA from the synaptic cleft into the presynaptic axon terminal. This study localized DATs to the hypothalamo-pituitary axis and evaluated the effect of DAT blockade on the hypothalamo-pituitary regulation of PRL. After 7 days of treatment with cocaine (a nonspecific amine transporter blocker) or mazindol (a specific DAT blocker), the relative abundance of PRL messenger RNA (mRNA) in the anterior lobe (AL) of OVX rats was significantly decreased, whereas the relative abundance of tyrosine hydroxylase mRNA in the hypothalamus was significantly increased. The effect of cocaine or mazindol administration on DA turnover and serum PRL concentration was examined in estradiol (E₂)- treated OVX rats. E₂ administration (iv) resulted in a significant increase in serum PRL within 4 h; however, cocaine or mazindol administration abolished the E₂-induced increase of PRL. Cocaine or mazindol significantly increased the concentration of DA at the site of the axon terminals within the median eminence (ME), intermediate lobe (IL) and neural lobe (NL), indicating blockade of uptake. Because formation of DOPAC requires uptake of DA, concentrations of DOPAC in the ME, IL and NL decreased following treatment with either cocaine or mazindol. These data, together with the presence of immunopositive DAT in the ME, pituitary stalk, IL, and NL, suggest that a functional DAT system is present within all three populations of NEDA neurons. Moreover, similarity between the effects of cocaine and mazindol treatment indicate that blockade of the DAT, but not other amine transporters, is responsible for suppression of PRL gene expression and secretion. Blockade of DATs prevent uptake of DA into NEDA neurons and consequently increases the amount of DA that diffuses into the portal vasculature and reaches the AL. These data provide evidence that DATs play a physiological role in the regulation of DA release from and TH expression in NEDA neurons and consequently PRL secretion and PRL gene expression and further support our previous observation that the regulation of PRL secretion involves all three populations of NEDA neurons.

This article has been cited by other articles:

				H. B. Patisaul, A. E. Fortino, and E. K. Polston Sex Differences in Serotonergic But Not {gamma}-Aminobutyric Acidergic (GABA) Projections to the Rat Ventromedial Nucleus of the Hypothalamus Endocrinology, January 1, 2008; 149(1): 397 - 408. [Abstract] [Full Text] [PDF]

				A. Jaubert, G. Drutel, T. Leste-Lasserre, F. Ichas, and L. Bresson-Bepoldin Tyrosine Hydroxylase and Dopamine Transporter Expression in Lactotrophs from Postlactating Rats: Involvement in Dopamine-Induced Apoptosis Endocrinology, June 1, 2007; 148(6): 2698 - 2707. [Abstract] [Full Text] [PDF]

				N. K. Mello, J. H. Mendelson, S. S. Negus, and M. Kelly Ovarian Steroid Hormone Modulation of the Acute Effects of Cocaine on Luteinizing Hormone and Prolactin Levels in Ovariectomized Rhesus Monkeys J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 156 - 167. [Abstract] [Full Text] [PDF]

				N. Ben-Jonathan and R. Hnasko Dopamine as a Prolactin (PRL) Inhibitor Endocr. Rev., December 1, 2001; 22(6): 724 - 763. [Abstract] [Full Text] [PDF]

				Z. B. Andrews, I. C. Kokay, and D. R. Grattan Dissociation of Prolactin Secretion from Tuberoinfundibular Dopamine Activity in Late Pregnant Rats Endocrinology, June 1, 2001; 142(6): 2719 - 2724. [Abstract] [Full Text] [PDF]

				M. E. Freeman, B. Kanyicska, A. Lerant, and G. Nagy Prolactin: Structure, Function, and Regulation of Secretion Physiol Rev, October 1, 2000; 80(4): 1523 - 1631. [Abstract] [Full Text] [PDF]