Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Tyrosine Hydroxylase Neurons Regulate Growth Hormone Secretion via Short-Loop Negative Feedback

Texto completo
Autor(es):
Wasinski, Frederick [1] ; Pedroso, Joao A. B. [1] ; dos Santos, Willian O. [1] ; Furigo, Isadora C. [1] ; Garcia-Galiano, David [2] ; Elias, Carol F. [2] ; List, Edward O. [3, 4] ; Kopchick, John J. [3, 4] ; Szawka, Raphael E. [5] ; Donato Jr, Jose
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 - USA
[3] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 - USA
[4] Ohio Univ, Heritage Coll Osteopath Med, Athens, OH 45701 - USA
[5] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Fisiol & Biofis, BR-31270901 Belo Horizonte, MG - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF NEUROSCIENCE; v. 40, n. 22, p. 4309-4322, MAY 27 2020.
Citações Web of Science: 0
Resumo

Classical studies suggest that growth hormone (GH) secretion is controlled by negative-feedback loops mediated by GH-releasing hormone (GHRH)- or somatostatin-expressing neurons. Catecholamines are known to alter GH secretion and neurons expressing TH are located in several brain areas containing GH-responsive cells. However, whether TH-expressing neurons are required to regulate GH secretion via negative-feedback mechanisms is unknown. In the present study, we showed that between 50% and 90% of TH-expressing neurons in the periventricular, paraventricular, and arcuate hypothalamic nuclei and locus ceruleus of mice exhibited STAT5 phosphorylation (pSTAT5) after an acute GH injection. Ablation of GH receptor (GHR) from TH cells or in the entire brain markedly increased GH pulse secretion and body growth in both male and female mice. In contrast, GHR ablation in cells that express the dopamine transporter (DAT) or dopamine beta-hydroxylase (DBH; marker of noradrenergic/adrenergic cells) did not affect body growth. Nevertheless, less than 50% of TH-expressing neurons in the hypothalamus were found to express DAT. Ablation of GHR in TH cells increased the hypothalamic expression of Ghrh mRNA, although very few GHRH neurons were found to coexpress TH- and GH-induced pSTAT5. In summary, TH neurons that do not express DAT or DBH are required for the autoregulation of GH secretion via a negative-feedback loop. Our findings revealed a critical and previously unidentified group of catecholaminergic interneurons that are apt to sense changes in GH levels and regulate the somatotropic axis in mice. (AU)

Processo FAPESP: 16/20897-3 - Papel dos neurônios orexina como mediadores dos efeitos centrais induzidos pelo hormônio do crescimento
Beneficiário:Frederick Wasinski
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 17/02983-2 - Ação do hormônio do crescimento no sistema nervoso: relevância para as funções neurais e na doença
Beneficiário:Jose Donato Junior
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/09679-4 - Estudo dos efeitos centrais do hormônio do crescimento sobre o metabolismo energético e controle glicêmico
Beneficiário:Isadora Clivatti Furigo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado