Dopamine transporters participate in the physiological regulation of prolactin

Jamie E. Demaria, György M. Nagy, Anna A. Lerant, M. Fekete, Cathy W. Levenson, Marc E. Freeman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)366-374
Number of pages9
JournalEndocrinology
Volume141
Issue number1
DOIs
Publication statusPublished - 2000

Fingerprint

Dopamine Plasma Membrane Transport Proteins
Mazindol
Prolactin
Dopaminergic Neurons
Dopamine
Cocaine
Posterior Pituitary Gland
Median Eminence
Presynaptic Terminals
3,4-Dihydroxyphenylacetic Acid
Pituitary Gland
Amines
Population
Gene Expression
Messenger RNA
Arcuate Nucleus of Hypothalamus
Tyrosine 3-Monooxygenase
Serum
Hypothalamus
Estradiol

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Demaria, J. E., Nagy, G. M., Lerant, A. A., Fekete, M., Levenson, C. W., & Freeman, M. E. (2000). Dopamine transporters participate in the physiological regulation of prolactin. Endocrinology, 141(1), 366-374. https://doi.org/10.1210/en.141.1.366

Dopamine transporters participate in the physiological regulation of prolactin. / Demaria, Jamie E.; Nagy, György M.; Lerant, Anna A.; Fekete, M.; Levenson, Cathy W.; Freeman, Marc E.

In: Endocrinology, Vol. 141, No. 1, 2000, p. 366-374.

Research output: Contribution to journalArticle

Demaria, JE, Nagy, GM, Lerant, AA, Fekete, M, Levenson, CW & Freeman, ME 2000, 'Dopamine transporters participate in the physiological regulation of prolactin', Endocrinology, vol. 141, no. 1, pp. 366-374. https://doi.org/10.1210/en.141.1.366
Demaria, Jamie E. ; Nagy, György M. ; Lerant, Anna A. ; Fekete, M. ; Levenson, Cathy W. ; Freeman, Marc E. / Dopamine transporters participate in the physiological regulation of prolactin. In: Endocrinology. 2000 ; Vol. 141, No. 1. pp. 366-374.
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