Modulation of calcitriol and IGF 1 synthesis by dietary nitrogen in young goats

• Applicant: Dr. Alexandra Muscher-Banse
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry ; Veterinary Medical Science
• Term: from 2012 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 230858041

Dietary nitrogen (N) reduction leads to a decrease in intestinal calcium (Ca) absorption and therefore reduced plasma Ca concentrations in young goats. Diminished Ca absorption is based on a reduced expression of Ca transporting proteins in the intestinal epithelium mediated by reduced plasma calcitriol concentrations. The reason for low plasma calcitriol concentrations during dietary N reduction is a decrease in insulin-like-growth-factor-1 (IGF1) concentrations. Aim of the present study is to characterise the underlying mechanisms leading to modulated renal calcitriol and hepatic IGF1 synthesis in goats on an N reduced diet. Therefore, expression of the hepatic 25-hydroxylase, responsible for calcidiol synthesis, renal 1alpha-hydroxylase and 24-hydroxylase, involved in synthesis and degradation of calcitriol, respectively, are examined. IGF1 and growth hormone (GH) are hormones of the somatotropic axis. Therefore, the amplitude, amount and frequency of GH secretion from the pituitary are measured to determine changes in these parameters as one possible explanation for reduced IGF1 plasma concentrations during dietary N reduction. Additionally, these measurements can give information about the impact of GH on IGF1 synthesis and a potential decoupling of these processes in young goats receiving N reduced diets. Expression of the hepatic GH receptor and intracellular GH-signalling proteins are determined to examine if a reduced dietary N amount alters IGF1 action via altered expression of these structures. The amount of renal IGF1 receptor expression is determined during dietary N reduction to evaluate if receptor adaptation takes place because of reduced plasma IGF1 concentrations. In addition, concentration and composition of IGF1 binding proteins in plasma are measured as determinants of distribution and duration of action of IGF1 to evaluate potential changes in this system during dietary N reduction in young goats. Described investigations are likely to improve the comprehension of the effects of an N reduced diet on the hypothalamic-pituitary axis (especially GH and IGF1) as an explanation for the already known changes of calcitriol synthesis in young goats during this feeding regime. Knowledge about changed expression of modulators of calcitriol and IGF1 synthesis can help to better understand resulting consequences such as reduced plasma calcitriol concentrations and therefore reduced intestinal Ca absorption and diminished plasma Ca levels and as a consequence alteration of further metabolic pathway like bone metabolism.

• DFG Programme: Research Grants