PARACRINE ACTIONS OF OXYTOCIN, PROSTAGLANDIN-F2-ALPHA, AND ESTRADIOL WITHIN THE HUMAN CORPUS-LUTEUM

Human luteal cells are known to interact in an auto- and paracrine fashion using a variety of substances, including prostaglandins (PGs), steroids, and peptides. In cultures of dispersed luteal cells obtained from several animal species prostaglandin F2-alpha (PGF2-alpha) and oxytocin (OXT) inhibit progesterone (P) secretion, indicating a luteloytic effect of these substances. The disadvantage of luteal cell cultures is that the different luteal cell types do not communicate with each other, i.e. auto- and paracrine effects cannot be studied. Therefore, we used a microdialysis tubing, which is implanted in human corpora lutea (CL) kept under short term organ culture conditions. Ringer's solution is pumped through the dialysis tubing, and substances secreted by the luteal tissue can be determined in the effluent fractions. This system also allows topical application of substances with putative intraluteal effects. In the present report we used PGF2-alpha, OXT, and estradiol (E2) to examine the effects of these substances on the respective other hormones and on P release from young human CL. Intraluteal application of PGF2-alpha stimulated OXT, E2, and P release. OXT was stimulatory to E2 and P secretion, an effect that can be blocked by a specific OXT antagonist and by tamoxifen. Elevation of intraluteal E2 concentrations also had marked stimulatory effects on P secretion. From luteal cell culture experiments it is known that PGF2-alpha and OXT have direct inhibitory effects on P production, but both substances stimulate E2 release. It was also shown that E2 counteracts the inhibitory effects on P release. Therefore, the PGF2-alpha- and OXT-induced E2 release may be responsible for the increased P release. This assumption is further substantiated by the observation that intraluteally applied E2 stimulates P secretion, and preexposure of human CL to tamoxifen prevents the OXT-induced stimulation of P, but not E2, secretion. We conclude that in young human CL, PGF2-alpha and OXT have dual effects: direct inhibitory effects on P release and E2-mediated stimulatory effects, which in young CL result in a net stimulation of P secretion.