Effects of the Isolated and Combined Ablation of Growth Hormone and IGF-1 Receptors in Somatostatin Neurons

Author(s):Show less -

Chaves, Fernanda M. ; Wasinski, Frederick ; Tavares, Mariana R. ; Mansano, Naira S. ; Frazao, Renata ; Gusmao, Daniela O. ; Quaresma, Paula G. F. ; Pedroso, Joao A. B. ; Elias, Carol F. ; List, Edward O. ; Kopchick, John J. ; Szawka, Raphael E. ; Donato Jr, Jose

• Document type: Journal article
• Source: Endocrinology; v. 163, n. 5, p. 13-pg., 2022-05-01.

Abstract

Hypophysiotropic somatostatin (SST) neurons in the periventricular hypothalamic area express growth hormone (GH) receptor (GHR) and are frequently considered as the key neuronal population that mediates the negative feedback loop controlling the hypothalamic-GH axis. Additionally, insulin-like growth factor-1 (IGF-1) may also act at the hypothalamic level to control pituitary GH secretion via long-loop negative feedback. However, to the best of our knowledge, no study so far has tested whether GHR or IGF-1 receptor (IGF1R) signaling specifically in SST neurons is required for the homeostatic control of GH secretion. Here we show that GHR ablation in SST neurons did not impact the negative feedback mechanisms that control pulsatile GH secretion or body growth in male and female mice. The sex difference in hepatic gene expression profile was only mildly affected by GHR ablation in SST neurons. Similarly, IGF1R ablation in SST neurons did not affect pulsatile GH secretion, body growth, or hepatic gene expression. In contrast, simultaneous ablation of both GHR and IGF1R in SST-expressing cells increased mean GH levels and pulse amplitude in male and female mice, and partially disrupted the sex differences in hepatic gene expression. Despite the increased GH secretion in double knockout mice, no alterations in body growth and serum or liver IGF-1 levels were observed. In summary, GHR and IGF1R signaling in SST neurons play a redundant role in the control of GH secretion. Furthermore, our results reveal the importance of GH/IGF-1 negative feedback mechanisms on SST neurons for the establishment of sex differences in hepatic gene expression profile. (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 Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/25281-3 - Effects of growth hormone on POMC, cholinergic and hypothalamic paraventricular nucleus neurons: implications for energy and glycemic metabolism control
• Grantee: Paula Gabriele Fernandes Quaresma Bergonsi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions
• Grantee: Jose Donato Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/10102-9 - Study of the effects induced by GH receptor ablation in neurons of the lateral hypothalamic area
• Grantee: Mariana Rosolen Tavares
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/21707-1 - Food deprivation effects in kisspeptin neurons excitability
• Grantee: Renata Frazão
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/21854-9 - Investigation of pro- and anti-inflamatory cytokines in biophysical properties of POMC and AgRP neurons of the arcuate nucleus of the hypothalamus
• Grantee: Fernanda Machado Chaves
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/22189-9 - Does the factors that change food intake modulate the activity of Kiss1 neurons?
• Grantee: Naira da Silva Mansano
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 21/03316-5 - Evaluation of the importance of GABAergic and dopaminergic transmission in neurons that express the growth hormone-releasing hormone to the control of GH secretion
• Grantee: Daniela de Oliveira Gusmão
• Support Opportunities: Scholarships in Brazil - Post-Doctoral