This study was conducted to analyze the roles of prolactin (PRL) and progesterone in the induction of luteal cell apoptosis and accumulation of macrophages in the regressing corpus luteum. We studied the number of apoptotic cells and macrophages in regressing corpora lutea in estrus 1) in cycling rats or after blocking PRL secretion with the dopaminergic agonist CB154, and 2) after blocking progesterone actions with the progesterone receptor antagonists RU-486 or ZK98299. Cells showing the morphological features characteristic of apoptosis contained fragmented DNA as indicated by in situ 3′ end labeling.
In cycling rats, a 100-fold increase in the number of apoptotic cells and a 4-fold increase in the number of macrophages was found from the evening (1600 h) of proestrus to the morning (1100 h) of estrus. Both increases were blocked by PRL suppression with CB154. Furthermore, blocking progesterone actions with progesterone receptor antagonists RU-486 or ZK98299 without affecting PRL secretion inhibited apoptosis but did not affect the accumulation of macrophages, whether treatment was started on the morning of metestrus (blocking diestrous and proestrous progesterone) or on proestrus (blocking only proestrous progesterone). Otherwise, exogenous progesterone was not effective in inducing apoptosis in the absence of PRL. These results indicate that both PRL and progesterone in proestrus are necessary for the induction of apoptosis in the regressing corpora lutea, whereas the accumulation of macrophages seemed to be dependent exclusively on the PRL surge.