Conditional Deletion of the Prolactin Receptor Reveals Functional Subpopulations of Dopamine Neurons in the Arcuate Nucleus of the Hypothalamus
| Autor: | Amanda Wyatt, Sharon R Ladyman, Papillon Gustafson, Hollian R Phillipps, Paul LeTissier, Caroline M. Larsen, David R. Grattan, Ilona C. Kokay, Penelope J. Knowles, Rosemary S E Brown, Siew Hoong Yip |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty RNA Untranslated Receptors Prolactin Green Fluorescent Proteins Radioimmunoassay Mice Transgenic Biology Statistics Nonparametric Prolactin cell 03 medical and health sciences 0302 clinical medicine Dopamine Arcuate nucleus Internal medicine STAT5 Transcription Factor medicine Animals RNA Messenger gamma-Aminobutyric Acid Tyrosine hydroxylase Glutamate Decarboxylase Dopaminergic Neurons General Neuroscience Prolactin receptor Arcuate Nucleus of Hypothalamus Articles Prolactin Rats Mice Inbred C57BL 030104 developmental biology Endocrinology Gene Expression Regulation nervous system Hypothalamus GABAergic Female 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Brown, R S E, Kokay, I C, Phillipps, H R, Yip, S H, Gustafson, P, Wyatt, A, Larsen, C M, Knowles, P, Ladyman, S R, Le Tissier, P & Grattan, D R 2016, ' Conditional Deletion of the Prolactin Receptor Reveals Functional Subpopulations of Dopamine Neurons in the Arcuate Nucleus of the Hypothalamus ', Journal of Neuroscience, vol. 36, no. 35, pp. 9173-85 . https://doi.org/10.1523/JNEUROSCI.1471-16.2016 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.1471-16.2016 |
| Popis: | UNLABELLED: Tuberoinfundibular dopamine (TIDA) neurons, known as neuroendocrine regulators of prolactin secretion from the pituitary gland, also release GABA within the hypothalamic arcuate nucleus. As these neurons express prolactin receptors (Prlr), prolactin may regulate GABA secretion from TIDA neurons, potentially mediating actions of prolactin on hypothalamic function. To investigate whether GABA is involved in feedback regulation of TIDA neurons, we examined the physiological consequences of conditional deletion of Prlr in GABAergic neurons. For comparison, we also examined mice in which Prlr were deleted from most forebrain neurons. Both neuron-specific and GABA-specific recombination of the Prlr gene occurred throughout the hypothalamus and in some extrahypothalamic regions, consistent with the known distribution of Prlr expression, indicative of knock-out of Prlr. This was confirmed by a significant loss of prolactin-induced phosphorylation of STAT5, a marker of prolactin action. Several populations of GABAergic neurons that were not previously known to be prolactin-sensitive, notably in the medial amygdala, were identified. Approximately 50% of dopamine neurons within the arcuate nucleus were labeled with a GABA-specific reporter, but Prlr deletion from these dopamine/GABA neurons had no effect on feedback regulation of prolactin secretion. In contrast, Prlr deletion from all dopamine neurons resulted in profound hyperprolactinemia. The absence of coexpression of tyrosine hydroxylase, a marker for dopamine production, in GABAergic nerve terminals in the median eminence suggested that rather than a functional redundancy within the TIDA population, the dopamine/GABA neurons in the arcuate nucleus represent a subpopulation with a functional role distinct from the regulation of prolactin secretion.SIGNIFICANCE STATEMENT: Using a novel conditional deletion of the prolactin receptor, we have identified functional subpopulations in hypothalamic dopamine neurons. Although commonly considered a uniform population of neuroendocrine neurons involved in the control of prolactin secretion, we have shown that approximately half of these neurons express GABA as well as dopamine, but these neurons are not necessary for the feedback regulation of prolactin secretion. The absence of tyrosine hydroxylase in GABAergic nerve terminals in the median eminence suggests that only the non-GABAergic dopamine neurons are involved in the control of pituitary prolactin secretion, and the GABAergic subpopulation may function as interneurons within the arcuate nucleus to regulate other aspects of hypothalamic function. |
| Databáze: | OpenAIRE |
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