Endometrial phospholipase A2 enzymes and their regulation by steroid hormones

The presence of two phospholipase A2 (PLA2) enzymes, designated PLA2(i) and PLA2(ii), has been demonstrated in human endometrium. These enzymes differ with respect to pH and calcium requirements, location within the tissue and regulation by steroid hormones. Phospholipase A2(i) is calcium dependent, optimally active at pH 7.5-9.0 and present mainly in the glandular component of the endometrium. Changes in activity occur during the menstrual cycle which are indicative of regulation by ovarian steroids. Conversely, PLA2(ii) is calcium independent, optimally active at pH 7.0 and located predominantly in the stromal layer. Wide variation in PLA2(ii) activity was found between individual subjects and there was no relationship with the stage of the menstrual cycle. Activity was, however, much higher in pathological endometrium and in endometrium from subjects with severe dysmenorrhoea. Triton X-100 activated PLA2(i) but not PLA2(ii). In cultured explants of endometrium, both enzymes were inhibited by progesterone whereas oestradiol and dexamethasone had no effect. However, progesterone priming followed by treatment with oestradiol caused a 2-fold stimulation of PLA2(i) but not PLA2(ii). Phospholipase A2 is favoured as the rate-limiting step in the generation of arachidonic acid for prostaglandin synthesis. However, our studies so far do not support a direct relationship between PLA2 and endometrial concentrations of prostaglandins, which implies that other important regulatory steps are involved. Other enzymes which are potentially capable of mobilizing arachidonic acid should also be investigated.