Dietary protein and calcium modulate parathyroid vitamin D receptor expression in young ruminants

Abstract

For economic reasons and in order to minimize nitrogen excretion and thus pollution, the crude protein content in the diet of livestock animals should be as low as possible without negatively affecting the animals´ health and performance. As ruminants can efficiently use dietary protein because of the ruminohepatic circulation of urea, they are considered to cope more easily with such a feeding regime than monogastric animals. However, despite unaltered daily weight gain, massive changes in mineral homeostasis and vitamin D metabolism were observed with dietary protein reduction (N-) in young, growing goats. Serum concentrations of 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) were decreased with a low N intake, even if calcium (Ca) was also restricted (Ca-). Interestingly, concentrations of cyclic adenosine monophosphate (cAMP) measured as an indirect assessment for the parathyroid hormone (PTH) activity were not affected by low protein. Therefore, it was hypothesized that the sensitivity of the parathyroid gland is modulated during these dietary interventions. Four groups of male German colored goats received a control (N+/Ca+), a reduced protein (N-/Ca+), a reduced Ca (N+/Ca-) or a reduced protein and Ca (N-/Ca-) diet. After six weeks we determined the expression of PTH, PTH receptor, Ca sensing receptor (CASR), vitamin D receptor (VDR), retinoid X receptor (RXRα), Klotho, fibroblast growth factor receptor 1c-splicing form, and the sodium-dependent P_i transporter (PiT1) in the parathyroid glands. Concentrations of cAMP were not affected, while those of Ca and 1,25-(OH)₂D₃were diminished and that of 25-hydroxyvitamin D₃ was increased with N- feeding. The expression patterns of the described target genes were not altered. In contrast, animals fed the Ca- rations showed enhanced serum 1,25-(OH)₂D₃ and cAMP levels with no changes in blood Ca concentrations demonstrating an efficient adaptation. The mRNA expression of expression of VDR and CASR in the parathyroid gland was significantly diminished and RXRα, PTHR and PiT1 expression was elevated. Instead of the assumed desensitization of the parathyroid gland with N-, our results indicate elevated responsiveness to decreased blood Ca with feeding Ca-.

Keywords: Calcium sensing receptor; Goat; Nitrogen; Parathyroid gland; Sodium-dependent P(i) transporter 1; Vitamin D receptor.