Central growth hormone action regulates metabolism during pregnancy

Pryscila D.S. Teixeira, Gisele C. Couto, Isadora C. Furigo, Edward O. List, John J. Kopchick, Jose Donato

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

The maternal organism undergoes numerous metabolic adaptations to become prepared for the demands associated with the coming offspring. These metabolic adaptations involve changes induced by several hormones that act at multiple levels, ultimately influencing energy and glucose homeostasis during pregnancy and lactation. Previous studies have shown that central growth hormone (GH) action modulates glucose and energy homeostasis. However, whether central GH action regulates metabolism during pregnancy and lactation is still unknown. In the present study, we generated mice carrying ablation of GH receptor (GHR) in agouti-related protein (AgRP)-expressing neurons, in leptin receptor (LepR)-expressing cells or in the entire brain to investigate the role played by central GH action during pregnancy and lactation. AgRP-specific GHR ablation led to minor metabolic changes during pregnancy and lactation. However, while brain-specific GHR ablation reduced food intake and body adiposity during gestation, LepR GHR knockout (KO) mice exhibited increased leptin responsiveness in the ventromedial nucleus of the hypothalamus during late pregnancy, although their offspring showed reduced growth rate. Additionally, both Brain GHR KO and LepR GHR KO mice had lower glucose tolerance and glucosestimulated insulin secretion during pregnancy, despite presenting increased insulin sensitivity, compared with control pregnant animals. Our findings revealed that during pregnancy central GH action regulates food intake, fat retention, as well as the sensitivity to insulin and leptin in a cell-specific manner. Together, the results suggest that GH acts in concert with other "gestational hormones" to prepare the maternal organism for the metabolic demands of the offspring.

Original languageEnglish
Pages (from-to)E925-E940
Number of pages16
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume317
Issue number5
DOIs
Publication statusPublished - 1 Nov 2019
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the São Paulo Research Foundation [FAPESP-Brazil, Grants 16/09679-4 (to I. Furigo), 17/02983-2 (to J. Donato), and 17/04006-4 (to G. Couto)], Conselho Nacional de Desenvolvimento Científico e Tecnológico [CNPq-Brazil, Grant 160186/2015-3 (to P. Teixeira)] and National Institute on Aging Grant R01-AG-059779 (to J. Kopchick and E. List).

Publisher Copyright:
© 2019 American Physiological Society. All rights reserved.

Keywords

  • Food intake
  • Gestation
  • Glucose homeostasis
  • Hypothalamus
  • Leptin resistance

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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