Intraovarian regulation of luteolysis

The corpus luteum is a transient gland, which is only functional for 17-18 days in the cyclic cow or for up to 200 days in the pregnant cow.Regression of the corpus luteum is essential for normal cyclicity as it allows the development of a new ovulatory follicle, whereas prevention of luteolysis is necessary for the maintenance of pregnancy Evidence acquired over the past three decades indicated that PGF2" is the luteolytic hormone in ruminants.Nevertheless, the detailed mechanisms of PGF," action are just beginning to be clarified.A pivotal role for an endothelial cell product endothelin 1 (ET-1) has been documented in PGF,"-induced luteal regression.ET-1 inhibited progesterone production by luteal cells in a dose-dependent manner via selective ET-1 binding sites (ETA).The inhibitory action of PGF2" on progesterone secretion (in vivo and in vitro) was blocked by a selective ETA receptor antagonist.This implied that ET-1 (through ETA receptors present on steroidogenic cells) may have mediated the inhibitory effect of PGF,".The involvement of ET-1 in luteal regression was also suggested by the observation that the highest concentrations of ET-1 coincide with uterine PGF2" surges.Furthermore, PGF," administration upregulated ET-1 expression within the corpus luteum.Later stages of luteal regression, which involve programmed cell death (PCD), are presumably mediated by immune cells.ET-1 may also be involved in this process by promoting leukocyte migration and stimulating macrophages to release tumour necrosis factor a (TNFa).The TIXITareceptor type 1 (p55) is present on luteal cells (endothelial and steroidogenic cells) and could initiate PCD and the structural demise of the corpus luteum.