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

Abstract

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-inducedprepartumluteolysis/abortion. The interrelationship between PGE2 and the ET system was investigated in PGE2-treated canine primary lutein cells from early CL.ET1did not change significantly over time;ET2,ECE1andETBwere elevated in early CL and were downregulated towards the mid/late-luteal phase. Theprepartumincrease ofET2was significant.ET3increased gradually, and was highest in late CL and/or atprepartumluteolysis.ETAremained constant until the late CL phase and increased only duringprepartumluteolysis. ET1 was localized to the luteal cells, andET2,ET3and ETA to vascular endothelium. ECE1 and ETB were detected at both locations. Except for upregulatedET1and lack of effect onET2,antigestagen applied to mid-pregnant dogs evoked similar changes to those observed during normal luteolysis. PGE2 upregulatedETBin treated cells;ETAandET1remained unaffected, andET2decreased. A modulatory role of the ETs in canine CL, possibly in association with other factors (e.g., PGE2 and progesterone receptor), is strongly indicated.