DECREASED ELASTIN SYNTHESIS IN NORMAL DEVELOPMENT AND IN LONG-TERM AORTIC ORGAN AND CELL-CULTURES IS RELATED TO RAPID AND SELECTIVE DESTABILIZATION OF MESSENGER-RNA FOR ELASTIN

We have previously shown that aortic organ cultures from 1- to 3-day-o ld chickens initially mimic the high levels of elastin production seen in vivo. However, more prolonged incubation of these tissues results in decreased synthesis of elastin. In the present study, we demonstrat e that decreased production of elastin in these aortic organ cultures is selective for elastin compared with collagen and is correlated with decreased steady state levels of mRNA for elastin. These decreases in steady state levels of elastin mRNA are due at least in part to a rap id and selective destabilization of mRNA for elastin, the half-life of which falls from approximate to 25 hours in fresh aortic tissues to a pproximate to 15 hours after incubation for only 8 hours. Destabilizat ion of elastin mRNA can be prevented by incubation in the presence of blockers of DNA transcription (5,6-dichlorobenzimidazole riboside and actinomycin D) and mRNA translation (cycloheximide). Furthermore, the half-life of aortic elastin mRNA decreases from approximate to 25 hour s in the 1-day-old chicken to approximate to 7 hours in the 8-week-old chicken, demonstrating that destabilization of mRNA is an important c ontributing factor in the decline in production of aortic elastin taki ng place during normal postnatal growth.