A screen for modulators reveals that orexin-A rapidly stimulates thyrotropin releasing hormone expression and release in hypothalamic cell culture.
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 GABABreceptor 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.
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico.
Antonieta
A
Cote-Vélez
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico.
Anabel
A
Martínez Báez
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico.
Leticia
L
Lezama
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico.
Rosa María
RM
Uribe
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico.
Patricia
P
Joseph-Bravo
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México (UNAM), Cuernavaca, Mor. 62271, Mexico. Electronic address: charli@ibt.unam.mx.
Jean-Louis
JL
Charli
D000818:Animals; D002478:Cells, Cultured; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism / Q000494:pharmacology*; D010907:Pituitary Hormones / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D007028:Hypothalamic Hormones; D008543:Melanins; D000068797:Orexins; D010907:Pituitary Hormones; D011498:Protein Precursors; D013973:Thyrotropin-Releasing Hormone; C019463:melanin-concentrating hormone; D013972:Thyrotropin; D011761:Pyrrolidonecarboxylic Acid
Endocannabinoid; Hypothalamus; Orexin; Paraventricular nucleus of hypothalamus; TRH