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

Endocrinology 2022 May 01

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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. © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Citation

Fernanda M Chaves, Frederick Wasinski, Mariana R Tavares, Naira S Mansano, Renata Frazao, Daniela O Gusmao, Paula G F Quaresma, João A B Pedroso, Carol F Elias, Edward O List, John J Kopchick, Raphael E Szawka, Jose Donato. Effects of the Isolated and Combined Ablation of Growth Hormone and IGF-1 Receptors in Somatostatin Neurons. Endocrinology. 2022 May 01;163(5)