EFFECTS OF PREGNANCY AND SYSTEMIC OR INTRAUTERINE OXYTOCIN INFUSION ON THE DISTRIBUTION OF ENDOMETRIAL OXYTOCIN RECEPTORS IN THE EWE - AN AUTORADIOGRAPHIC STUDY

Previous autoradiographic studies have suggested that the regulation o f oxytocin receptors differs between endometrial cell types during the ovine oestrous cycle, and that those present on luminal epithelial ce lls are of particular importance to the regulation of prostaglandin F2 alpha release during luteal regression. The present autoradiographic s tudy compares the distribution of the endometrial oxytocin receptor in day-15 non-pregnant and pregnant ewes. The distribution of the endome trial oxytocin receptor in day-15 non-pregnant ewes infused with syste mic or intrauterine oxytocin has also been investigated. Continuous, s .c. infusion of oxytocin (150 mmol/24 h) into ewes (n = 6) between day s 10 and 15 of the oestrous cycle significantly increased plasma oxyto cin concentrations (to approximately 100 pmol/1). There was no similar increase in systemic oxytocin concentrations in ewes receiving intrau terine (i.u.) oxytocin infusions (10 nmol/24 h) between days 10 and 15 of the oestrous cycle (n = 6). Luteolysis was inhibited in all six an imals infused with oxytocin (s.c.) and endometrial oxytocin receptor c oncentrations were significantly lower on day 15 in these animals (12. 8 +/- 6.5 (S.E.M.) fmol/mg protein; P<0.001) and in pregnant ewes (18. 4 +/- 15.4 fmol/mg protein; P<0.001; n=8) than in ewes infused with sa line (248.6 +/- 67.1 fmol/mg protein; n=6). While the I-125-labelled o xytocin receptor antagonist, [1-(beta-mercapto-beta,beta-cyclopentamet hylene propionic acid), 2-(ortho-methyl)-Tyr2, Thr4, Orn8, Tyr9-NH2]-v asotocin (I-125-labelled OTA) clearly labelled glandular epithelia, lu minal epithelium and caruncular stromal cells specifically on day 15 i n saline (s.c.)-infused ewes, such specific labelling appeared to be r educed or absent from pregnant animals and those infused with oxytocin (s.c.). A significant reduction in the density of labelling of carunc ular stroma (P<0.05) and luminal epithelium (P<0.001) was confirmed us ing quantitative densitometric analysis. The reduction in the labellin g of endometrium in oxytocin-infused ewes was not caused by the bindin g of exogenous oxytocin to endometrial binding sites. Oxytocin infusio n (i.u.) did not inhibit luteolysis, nor was there any significant dif ference in the endometrial oxytocin receptor concentration in this gro up of ewes on day 15 compared with those infused with saline (i.u.). T here was also clear specific labelling of luminal epithelial cells wit h I-125-labelled OTA in ewes receiving oxytocin infused i.u. and quant ification of autoradiograms failed to differentiate between these anim als and those infused with saline (i.u.). It was concluded that system ic oxytocin infusion and the early establishment of pregnancy led to a clear reduction in the endometrial oxytocin receptor concentration on luminal epithelial cells, glandular epithelial cells and caruncular s tromal cells, but that i.u. oxytocin infusions did not affect any of t hese receptor populations and notably not the luminal epithelial oxyto cin receptor. The results support the contention that the luminal epit helial oxytocin receptor is involved in the luteolytic process.