Abstract. Endothelin-1 (ET-1) is a luteolytic mediator in the bovine corpus luteum (CL), and its action appears to be via endothelin type A receptor (ETR-A). Thus, the aim of the present study was to determine the effect of ETR-A antagonist on PGF2α-induced luteolysis in the cow. Cows on days 10-12 of the estrous cycle were subjected to five intraluteal injections of the ETR-A antagonist LU 135252 in saline or only saline at -0.5, 2, 4, 6, and 8 h after PGF2α administration (=0 h). Serial luteal biopsies were conducted to determine the expression of mRNA in the luteal tissue. There were no significant differences in the decrease in plasma progesterone (P) concentrations and the mRNA expressions of steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase/∆ 5 , ∆ 4 -isomerase between the ETR-A antagonist-treated group and the control group. However, the start of the decline in CL volume and blood flow area surrounding the CL was delayed for almost two days in the ETR-A antagonist-treated group compared to the control group. The mRNA expression of preproET-1 and endothelin type B receptor increased in both groups, while the ETR-A mRNA remained unchanged. In addition, caspase-3 mRNA expression increased significantly at 24 h in the control group only and its level was higher than that of the ETR-A antagonist-treated group. Thus, the present study suggests that ET-1 regulates structural luteolysis via ETR-A by controlling blood vessel contraction in the CL of the cow. Key words: Apoptosis, Blood flow, Corpus luteum, Cow, Endothelin-1 (J. Reprod. Dev. 52: [551][552][553][554][555][556][557][558][559] 2006) he corpus luteum (CL) is a transient endocrine gland that secretes progesterone (P) to support pregnancy. If fertilization does not occur, the CL undergoes regression to induce the next ovulation. I n r u m i n a n t s , i t i s w e l l k n o w n t h a t t h e p r o s t a g l a n d i n ( P G ) F 2 α r el e a s e d f ro m t h e endometrium is a primary luteolysin [1]. A pulsatile release of physiological PGF 2α on days 17-18 (estrus=day 0) or an injection of exogenous PGF 2α during the mid-luteal phase of the estrous cycle induces a drastic decrease in the plasma P concentration followed by a gradual decline in blood flow to the CL and a decrease in the CL tissue [2-4]. However, our previous studies have i n d i c a t e d t h a t d i r e c t e x p o s u r e o f t h e microenvironment within the mid-CL to PGF 2α using an in vivo [5] and in vitro [6,7] microdialysis system (MDS) did not inhibit, but rather stimulated P secretion from the CL. These observations