Tyrosine hydroxylase neurons regulate growth hormone secretion via short-loop negative feedback
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Universidade Federal de Minas Gerais
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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 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.
Abstract
Assunto
Hormônios, Neuroendocrinologia, Biologia
Palavras-chave
Catecholamines, Dopamine, Hypothalamus, Neuroendocrinology, Neuropeptides, Somatotropic axis
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Endereço externo
https://www.jneurosci.org/content/40/22/4309.long