A screen for modulators reveals that orexin-A rapidly stimulates thyrotropin releasing hormone expression and release in hypothalamic cell culture
Por:
Cote-Vélez, A., Martínez Báez, A., Lezama, L., Uribe, R.M., Joseph-Bravo, P., Charli, J.-L.
Publicada:
1 abr 2017
Resumen:
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 (0.5-3 h) modified by synaptic inputs
onto TRH neurons; in some experiments, TRH cell content or release was
also analyzed. Various modulators, including histamine, serotonin,
beta-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
GABA(B) 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. (C) 2017 Elsevier Ltd. All rights reserved.
Filiaciones:
Cote-Vélez, A.:
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico
Martínez Báez, A.:
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico
Lezama, L.:
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico
Uribe, R.M.:
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico
Joseph-Bravo, P.:
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico
Charli, J.-L.:
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico
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