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

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF NEUROSCIENCE; v. 40, n. 22, p. 4309-4322, MAY 27 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 16/20897-3 - Role of orexin neurons as mediators of the central effects induced by growth hormone
• Grantee: Frederick Wasinski
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 17/02983-2 - The role of growth hormone in the brain: relevance for neural functions and in disease
• Grantee: Jose Donato Junior
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 16/09679-4 - Central effects of growth hormone on energetic metabolism and glicemic control
• Grantee: Isadora Clivatti Furigo
• Support type: Scholarships in Brazil - Post-Doctorate