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. Regressio n of the corpus luteum is essential for normal cyclicity as it allows the d evelopment of a new ovulatory follicle, whereas prevention of luteolysis is necessary for the maintenance of pregnancy. Evidence acquired over the pas t three decades indicated that PGF(2 alpha) is the luteolytic hormone in ru minants. Nevertheless, the detailed mechanisms of PGF(2 alpha) action are j ust beginning to be clarified. A pivotal role for an endothelial cell produ ct endothelin 1 (ET-1) has been documented in PGF(2 alpha)-induced luteal r egression. ET-1 inhibited progesterone production by luteal cells in a dose -dependent manner via selective ET-1 binding sites (ETA). The inhibitory ac tion of PGF(2 alpha) on progesterone secretion (in vivo and in vitro) was b locked by a selective ET, receptor antagonist. This implied that ET-1 (thro ugh ET, receptors present on steroidogenic cells) may have mediated the inh ibitory effect of PGF(2 alpha). The involvement of ET-l in luteal regressio n was also suggested by the observation that the highest concentrations of ET-1 coincide with uterine PGF(2 alpha) surges. Furthermore, PGF(2 alpha) a dministration upregulated ET-1 expression within the corpus luteum. Later s tages of luteal regression, which involve programmed cell death (PCD), are presumably mediated by immune cells. ET-1 may also be involved in this proc ess by promoting leukocyte migration and stimulating macrophages to release tumour necrosis factor alpha (TNF alpha). The TNF alpha receptor type 1 (p 55) is present on luteal cells (endothelial and steroidogenic cells) and co uld initiate PCD and the structural demise of the corpus luteum.