The effect of oxytocin, estrogen, calcium ionophore A23187 and hydrocortisone on prostaglandin F2 alpha and 6-oxo-prostaglandin F1 alpha production by cultured human endometrial and myometrial explants.
Normal human endometrium (classified by histology and date after last menstrual period) was cultured for 72h, and the output of prostaglandin F2 alpha and 6-oxo-prostaglandin F1 alpha detected by radioimmunoassay. Hormones/stimuli were added to the culture during the second day of culture for 5h and 19h periods. The output of prostaglandin F2 alpha from cultured endometrium was significantly higher (p less than 0.05) at the beginning (d4-8) and end (d25-30) of the menstrual cycle, compared to mid-cycle (d13-24) endometrium. Significantly more prostaglandin F2 alpha was released from proliferative than from secretory phase endometrium (p less than 0.02). Prostaglandin F2 alpha release was rapidly stimulated by sodium arachidonate (20-300 micrograms/ml), and by calcium ionophore A23187 (5 micrograms/ml) at an extracellular calcium ion concentration of 1.8mM. The ionophore stimulation was greater in mid-cycle endometrium than in endometrium from the beginning or the end of the menstrual cycle. Estradiol-17 beta (10 ng/ml) gradually increased the output of prostaglandin F2 alpha from secretory phase endometrium, and this stimulation was observed in the post-incubation period after hormone had been removed from the incubation medium. Oxytocin (1 X 10(-5) U/ml caused a more rapid stimulation of prostaglandin F2 alpha output from secretory phase tissue (p less than 0.05 during the first 5h incubation period with hormone). Oxytocin (1 X 10(-5) U/ml) and estradiol (10ng/ml) together significantly stimulated prostaglandin F2 alpha production by proliferative as well as secretory phase endometria. A high dose of hydrocortisone (100 micrograms/ml) inhibited the output of prostaglandin F2 alpha from proliferative and secretory phase endometrium and also from ionophore-stimulated endometrium. However, this dose of hydrocortisone did not inhibit the synthesis of prostaglandin F2 alpha from exogenous arachidonic acid, or the estradiol-induced increase in prostaglandin F2 alpha production. Co-culture of endometrium with myometrium did not modify the output of prostaglandin F2 alpha or of 6-oxo-prostaglandin F1 alpha from cultured tissues. These experiments suggest that arachidonic acid supply to the cyclooxygenase enzyme may vary during the menstrual cycle; and indicate a gradual increase in prostaglandin synthesising capacity in response to estrogen, more rapid control via oxytocin, and an interaction between estrogen and oxytocin to modulate prostaglandin F2 alpha synthesis in human endometrium.
D000001:Calcimycin / Q000494:pharmacology*; D046508:Culture Techniques; D015237:Dinoprost; D004717:Endometrium / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008598:Menstruation; D009215:Myometrium / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D011460:Prostaglandins F / Q000096:biosynthesis*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D004967:Estrogens; D011460:Prostaglandins F; D000001:Calcimycin; D010121:Oxytocin; D015237:Dinoprost; D006854:Hydrocortisone