Capacity of 1,25-dihydroxyvitamin D to stimulate expression of calbindin D changes with age in the rat

Studies in rats and humans have shown that there is an age-related decline in the stimulation of intestinal Ca transport by 1,25- dihydroxyvitamin D₃ [1,25(OH)₂D], the active metabolite of vitamin D. The calbindins are a family of vitamin D-dependent calcium-binding proteins found in the intestine (calbindin D-9k) and kidney (calbindin D-28k) and are thought to play a role in calcium transport and homeostasis. The purpose of this study was to determine if the capacity of 1,25(OH)₂D to stimulate the expression of calbindin protein and mRNA changes with age. Young (2 months), adult (12 months), and old (22 months) male F344 rats were made deficient in 1,25(OH)₂D by being fed a strontium-containing diet and then being given a single ip injection of 1,25(OH)₂D. Calbindin protein levels were measured by immunological techniques using specific antisera, and mRNA levels were measured by Northern and dot blots. The maximal amount of calbindin D-9k protein induced by 1,25(OH)₂D declined with age in the duodenum but not in the ileum. In time-course studies, there was a delay in calbindin D-9k induction in the duodenum but not in the ileum of adult rats compared to young rats. In contrast to protein induction, maximal calbindin D-9k mRNA levels in response to 1,25(OH)₂D were greater in the adult animal and showed no time lag compared to those in the young animal. In the kidney, maximal levels of renal calbindin D-28k protein and mRNA did not change with age, but there was delayed induction in the adult. These studies demonstrate mRNA into protein in the duodenum with age.