Increased intestinal chromatin template activity. Influence of 1α,25 dihydroxyvitamin D₃ and hormone receptor complexes

1α,25 Dihydroxyvitamin D₃ administration to rachitic chicks results in an increase in the chromatin template activity of intestinal target tissue assayed in vitro using Escherichia coli RNA polymerase. The maximum stimulation of template capacity was 12 to 20% over control values and occurred 2 hours after administration of the sterol. This rapid effect preceded the biologic response to 1α,25 dihydroxyvitamin D₃ in the intestine and was not observed in other tissues such as liver or kidney. The in vivo enhancement of intestinal chromatin template activity was specific for the 1α,25 dihydroxyvitamin D₃ hormone in that equivalent doses of 25 hydroxyvitamin D₃ or vitamin D₃ did not elicit a response in 2 to 3 hours. Only 1α hydroxyvitamin D₃, a synthetic sterol which is very rapidly metabolized to the 1α,25 dihydroxyvitamin D₃ form, was able to mimic the natural hormone in vivo. To further elucidate the nuclear mechanism of action of 1α,25 dihydroxyvitamin D₃, the hormone was preincubated at 0° with intestinal cytosol to form hormone receptor complexes. After addition of the hormone receptor complexes to purified intestinal mucosa nuclei and incubation for 1 hour at 25°, chromatin isolated from this reconstituted system displayed a significant increase in template activity as compared to chromatin prepared from similar in vitro incubations not containing hormone. This stimulation was 12 to 24% over control values and exhibited an absolute requirement for intestinal cell cytosol. The response was specific for physiologic levels of 1α,25 dihydroxyvitamin D₃, but occurred with pharmacologic doses of 25 hydroxyvitamin D₃. It is concluded that a stimulation of the chromatin template activity of intestinal target tissue by a 1α,25 dihydroxyvitamin D₃ may be an integral part of the ultimate physiologic response of enhanced calcium transport.