Impairment of protein synthesis in the rat uterus following intrauterine delivery of indomethacin.

When indomethacin was incorporated into a slow-release preparation (initial content 1.6 mg drug) and placed in one horn of the rat uterus, a significant decrease in protein synthesis occurred for this horn in comparison with control animals (as determined by the incorporation of radioactive leucine) at three different times after insertion. Decreases of 20, 21% at the two times of dioestrus and 28% at the time of oestrus selected were determined. No significant reduction in protein synthesis was found for the contralateral horn, although there was a tendency for it to be lowered at the earliest time of examination when two complete oestrous cycles had passed following insertion. Measurement of the uptake of radioactive leucine by the uterine horns showed no change in response to indomethacin delivery compared to the control animals with silastic implants, and suggested that the transport system for this amino acid in cells of the uterine horns was not affected by the drug. It was apparent that in instances when the protein synthesis of the uterine horn was impaired by indomethacin that a decrease in RNA/DNA ratio existed. At the latest time examined, no alteration in DNA content occurred in the indomethacin-influenced horn but there was a significant reduction in RNA content. For a small proportion of the animals with indomethacin-releasing preparations there was a tendency to show a lengthening of the oestrous cycle over the first three cycles following insertion. Whether this was due to a direct effect of indomethacin on the ovaries or an effect caused by decreased concentrations of prostaglandins in the uterus was unknown. 5 These results provide further evidence that non-steroidal anti-inflammatory drugs can interfere with the synthesis of macromolecular substances, and that such changes need to be taken into account when considering the overall effect of these drugs on tissues and organs.