Tyrosine hydroxylase neurons regulate growth hormone secretion via short-loop negative feedback

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dc.creatorFrederick Wasinski
dc.creatorJose Donato
dc.creatorJoão Pedroso
dc.creatorWillian dos Santos
dc.creatorIsadora Furigo
dc.creatorDavid Garcia-galiano
dc.creatorCarol Elias
dc.creatorEdward List
dc.creatorJohn Kopchick
dc.creatorRaphael Escorsim Szawka
dc.date.accessioned2025-01-20T20:38:22Z
dc.date.accessioned2025-09-09T00:15:00Z
dc.date.available2025-01-20T20:38:22Z
dc.date.issued2020-05-27
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1523/JNEUROSCI.2531-19.2020
dc.identifier.issn1529-2401
dc.identifier.urihttps://hdl.handle.net/1843/79336
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofThe Journal of Neuroscience
dc.rightsAcesso Aberto
dc.subjectHormônios
dc.subjectNeuroendocrinologia
dc.subjectBiologia
dc.subject.otherCatecholamines
dc.subject.otherDopamine
dc.subject.otherHypothalamus
dc.subject.otherNeuroendocrinology
dc.subject.otherNeuropeptides
dc.subject.otherSomatotropic axis
dc.titleTyrosine hydroxylase neurons regulate growth hormone secretion via short-loop negative feedback
dc.typeArtigo de periódico
local.citation.epage4322
local.citation.issue22
local.citation.spage4309
local.citation.volume40
local.description.resumoClassical 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 b-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.
local.identifier.orcidhttps://orcid.org/0000-0001-7310-6760
local.identifier.orcidhttps://orcid.org/0000-0002-4166-7608
local.identifier.orcidhttps://orcid.org/0000-0001-9506-8785
local.identifier.orcidhttps://orcid.org/0000-0002-8230-6331
local.identifier.orcidhttps://orcid.org/0000-0003-4561-2177
local.identifier.orcidhttps://orcid.org/0000-0002-2639-3469
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA
local.publisher.initialsUFMG
local.url.externahttps://www.jneurosci.org/content/40/22/4309.long

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