Expression and functional implications of luteal endothelins in pregnant and non-pregnant dogs

Luteal development is regulated by many locally produced mediators, e.g., prostaglandins and angiogenic factors. However, the role and function of vasoactive factors in the canine corpus luteum (CL) remain largely unknown. Consequently, expression of the endothelin (ET) receptors-A and -B (ETA and ETB, revealing vasoconstriction and vasodilator properties respectively), the ET-converting enzyme (ECE1) and ET1, -2 and -3 were investigated in CL from non-pregnant dogs (days 5, 15, 25, 35, 45 and 65 post-ovulation), and at selected stages of pregnancy (pre-implantation, post-implantation, mid-gestation), and during normal and antigestagen-induced prepartum luteolysis/abortion. The interrelationship between PGE2 and the ET system was investigated in PGE2-treated canine primary lutein cells from early CL. ET1 did not change significantly over time; ET2, ECE1 and ETB were elevated in early CL and were downregulated towards the mid/late-luteal phase. The prepartum increase of ET2 was significant. ET3 increased gradually, and was highest in late CL and/or at prepartum luteolysis. ETA remained constant until the late CL phase and increased only during prepartum luteolysis. ET1 was localized to the luteal cells, and ET2, ET3 and ETA to vascular endothelium. ECE1 and ETB were detected at both locations. Except for upregulated ET1 and lack of effect on ET2, antigestagen applied to mid-pregnant dogs evoked similar changes to those observed during normal luteolysis. PGE2 upregulated ETB in treated cells; ETA and ET1 remained unaffected, and ET2 decreased. A modulatory role of the ETs in canine CL, possibly in association with other factors (e.g., PGE2 and progesterone receptor), is strongly indicated