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

Abstract

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 i.p. 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 that there is an age-related decrease in the induction of calbindin protein in response to 1,25(OH)2D in the duodenum, but not in the ileum or kidney. This decline may be due to decreased translation of calbindin D-9k mRNA into protein in the duodenum with age.