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

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.

A reduced protein diet modulates enzymes of vitamin D and cholesterol metabolism in young ruminants.

Besides other adverse effects, a low protein diet has been shown to modulate cholesterol and vitamin D metabolism in monogastric species like rats and humans. As ruminants can increase the efficiency of the rumino-hepatic circulation of urea, it is assumed that goats should be able to compensate for a low dietary protein intake better. After a dietary protein restriction (9% vs. 20%) for six weeks, plasma concentrations of urea, albumin, 1,25-dihydroxyvitamin D3 and calcium were decreased, while plasma 25-hydroxyvitamin D3 (25-OHD3), and total cholesterol were significantly increased in young goats. Because this was not accompanied by any decrease in expression of CYP24A1 mRNA, we investigated mRNA expression of additional enzymes with known 24- and/or 25-hydroxylase activities (CYP2R1, CYP2J2, CYP3 A24, CYP27A1), receptors involved in their regulation (VDR, PXR, RXRα) and vitamin D binding protein (VDBP). CYP2R1expression was stimulated with the low dietary protein intake, negatively correlated with plasma urea and positively associated with serum 25-OHD3. The greater plasma concentrations of total cholesterol could be explained with the reduction of CYP2J2 and CYP27A1 expression. None of the receptors investigated were affected by the dietary protein restriction but mRNA expression of VDBP was slightly reduced. Taken together our results show that dietary protein restriction has an impact on vitamin D and cholesterol metabolism in ruminants, too. Therefore, further investigations are needed before dietary interventions aiming at diminishing nitrogen excretion can be implemented.