Modulation of growth hormone receptor-insulin-like growth factor 1 axis by dietary protein in young ruminants

Abstract

A reduced protein intake causes a decrease in insulin-like growth factor 1 (IGF1) concentrations and modulates Ca homoeostasis in young goats. IGF1 is synthesised by the liver in response to stimulation by growth hormone (GH). Due to rumino-hepatic circulation of urea, ruminants are suitable for investigating the effects of protein reduction despite sufficient energy intake. The present study aimed to investigate the impact of a protein-reduced diet on the expression of components of the somatotropic axis. Male young goats were divided into two feeding groups receiving either a control diet (20 % crude protein (CP)) or a reduced-protein diet (9 % CP). Blood concentrations of IGF1 and GH were measured, and a 24-h GH secretion profile was compiled. Moreover, ionised Ca and insulin concentrations as well as mRNA and protein expression levels of hepatic proteins involved in GH signalling were quantified. Due to the protein-reduced diet, concentrations of ionised Ca, insulin and IGF1 decreased significantly, whereas GH concentrations remained unchanged. Expression levels of the hepatic GH receptor (GHR) decreased during protein reduction. GHR expression was down-regulated due to diminished insulin concentrations as both parameters were positively correlated. Insulin itself might be reduced due to reduced blood Ca levels that are involved in insulin release. The protein-reduced diet had an impact on the expression of components of the somatotropic axis as a disruption of the GH-IGF1 axis brought about by diminished GHR expression was shown in response to a protein-reduced diet.

Calcium Homeostasis and Bone Metabolism in Goats Fed a Low Protein Diet

“…Meanwhile, different animal species may have various adaptations of the change of dietary protein levels. In goat studies, it has been reported that young male goats fed a reduced-protein for 6-8 weeks significantly reduced plasma Ca concentrations due to reduced intestinal Ca uptake and microbial metabolism (34)(35)(36), which was inconsistent with our results. The difference may be related with the different physiological state of the experimental goats gone through.…”

Transcriptomic and Metabolomic Analyses Reveal Inhibition of Hepatic Adipogenesis and Fat Catabolism in Yak for Adaptation to Forage Shortage During Cold Season

“…The possible reasons may be the abundant grass in the warm season, the average daily gain of the yak has been improved, and the growth and development of the animal body tend to mature with the increase in ADG, which gradually reduces the amount of protein synthesis in the body and increases fat deposition. Therefore, the role of GH is relatively weakened, and the serum GH concentration also decreases ( Firmenich et al, 2020 ). Serum triglyceride, total cholesterols, LDL, and HDL reflect the status or rate of lipid metabolism ( Huang et al, 2013 ).…”

Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers

“…Growth hormone is mainly produced by the anterior pituitary gland, secreted in a pulsatile manner and under direct control of hypothalamic neuronal projections ( Pombo et al, 2001 ), whose secretion is mainly regulated positively by growth hormone releasing hormone (GHRH), ghrelin ( Dimaraki and Jaffe, 2006 ; Khatib et al, 2014 ), and negatively by somatostatin (SS) ( Lu et al, 2019 ). Following release, the action of GH is achieved through binding with GH receptor (GHR), which is widely expressed in variety of tissues ( Møller and Jørgensen, 2009 ) and their interaction mainly results in the activation of JAK2/STAT5, MAPK-ERK1/2, PI3K-Akt, as well as PLC/PKC/Ca 2+ signaling pathways ( Zhu et al, 2001 ; Bocharov et al, 2018 ; Basu and Kulkarni, 2019 ; Chhabra et al, 2019 ) and the synthesis of IGF1 is mainly in liver ( Guevara-Aguirre et al, 2018 ; Zhang et al, 2019 ; Firmenich et al, 2020 ). In the GH signaling, GH binding proteins are produced at the cell surface and play complex roles, including modulate the half-life of plasma GH and the binding of GH to GHR ( Cawley et al, 2013 ).…”

“…In most cases, the growth-promoting effects of GH depend on IGF1. In general, GH promotes IGF1 gene transcription and synthesis in the liver, thus regulating the circulating levels of IGF1 ( Guevara-Aguirre et al, 2018 ; Firmenich et al, 2020 ). Hypophysectomized rats show a rapid increase in serum IGF1 after recombinant human GH (rhGH) administration, and a 75% reduction of circulating IGF1 levels due to the liver IGF1-deficient in mice leads to a fourfold increase in GH secretion ( Yakar et al, 2004 ).…”