A screen for modulators reveals that orexin-A rapidly stimulates thyrotropin releasing hormone expression and release in hypothalamic cell culture

Autor: Anabel Martínez Báez, Leticia Lezama, Antonieta Cote-Vélez, Rosa María Uribe, Patricia Joseph-Bravo, Jean-Louis Charli
Rok vydání: 2017
Předmět:
0301 basic medicine
endocrine system
medicine.medical_specialty
endocrine system diseases
Melanin-concentrating hormone
Hypothalamus
Thyroid Gland
Thyrotropin
Thyrotropin-releasing hormone
Kainate receptor
03 medical and health sciences
Cellular and Molecular Neuroscience
Orexin-A
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
Internal medicine
medicine
Animals
Protein Precursors
Rats
Wistar
Thyrotropin-Releasing Hormone
Cells
Cultured
Melanins
Neurons
Orexins
Hypothalamic Hormones
Endocrine and Autonomic Systems
Chemistry
General Medicine
Pyrrolidonecarboxylic Acid
Orexin
Pituitary Hormones
030104 developmental biology
Somatostatin
nervous system
Neurology
Paraventricular nucleus of hypothalamus
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Zdroj: Neuropeptides. 62:11-20
ISSN: 0143-4179
DOI: 10.1016/j.npep.2017.01.005
Popis: In the paraventricular nucleus of the mammalian hypothalamus, hypophysiotropic thyrotropin releasing hormone (TRH) neurons integrate metabolic information and control the activity of the thyroid axis. Additional populations of TRH neurons reside in various hypothalamic areas, with poorly defined connections and functions, albeit there is evidence that some may be related to energy balance. To establish extracellular modulators of TRH hypothalamic neurons activity, we performed a screen of neurotransmitters effects in hypothalamic cultures. Cell culture conditions were chosen to facilitate the full differentiation of the TRH neurons; these conditions had permitted the characterization of the effects of known modulators of hypophysiotropic TRH neurons. The major end-point of the screen was Trh mRNA levels, since they are generally rapidly (0.5-3h) modified by synaptic inputs onto TRH neurons; in some experiments, TRH cell content or release was also analyzed. Various modulators, including histamine, serotonin, β-endorphin, met-enkephalin, and melanin concentrating hormone, had no effect. Glutamate, as well as ionotropic agonists (kainate and N-Methyl-d-aspartic acid), increased Trh mRNA levels. Baclofen, a GABAB receptor agonist, and dopamine enhanced Trh mRNA levels. An endocannabinoid receptor 1 inverse agonist promoted TRH release. Somatostatin increased Trh mRNA levels and TRH cell content. Orexin-A rapidly increased Trh mRNA levels, TRH cell content and release, while orexin-B decreased Trh mRNA levels. These data reveal unaccounted regulators, which exert potent effects on hypothalamic TRH neurons in vitro.
Databáze: OpenAIRE
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