Effect of actinomycin D on prostaglandin synthesis by and output from the guinea-pig uterus.

The intra-uterine administration of actinomycin D on Day 10 reduced the output of prostaglandin (PG) F2 alpha (the major PG released) from the Day 15 guinea-pig uterus in vitro by 80 to 85%. PGE2 output was reduced by 50%, while 6-keto-PGF1 alpha output was unaffected. Plasma progesterone levels were high (3 to 15 ng/ml) on Day 15 due to the reduction in uterine PGF2 alpha output. Endometrial PGF2 alpha synthesizing capacity was reduced by 50% by actinomycin D treatment, while endometrial PGE2 and 6-keto-PGF1 alpha synthesizing capacities were unaffected. Oestradiol treatment in vivo did not reverse the inhibitory effects of actinomycin D on uterine PG production. A23187 increased uterine PGF2 alpha, 6-keto-PGF1 alpha and PGE2 outputs irrespective of treatment, indicating that substrate supply was always rate limiting. Actinomycin D inhibited the uterotrophic action of oestradiol indicating that fresh protein synthesis had been inhibited. Overall, this study suggests that increased protein synthesis is involved in stimulating endometrial PGF2 alpha synthesis and release. Previous studies have shown that increases in enzyme activities induced by oestradiol are only secondary events in the stimulation of endometrial PGF2 alpha production. We propose that oestradiol induces the synthesis of a protein ('lipostimulin') which, acting on a progesterone-primed uterus, "switches on" endometrial PGF2 alpha synthesis and release by causing the activation of endometrial phospholipase A2.