Fas/Fas ligand system in prolactin-induced apoptosis in rat corpus luteum:Possible role of luteal immune cells

The prolactin (PRL) surge in cycling rats during the proestrous afternoon i s an inducer of apoptotic cell death in luteal cells. This luteolytic actio n of PRL is peculiar, because PRL may be categorized as a survival factor, if other known physiological functions of PRL are taken into account. Here we analyzed the underlying molecular/cellular mechanisms of this PRL-induce d apoptosis. Corpora lutea (CL) were prepared from the ovary on the proestr ous day and cultured with or without PRL (2 mu g/ml). An addition of PRL to the culture medium induced DNA breakdown in the nuclei of cells mostly ide ntified as steroidogenic by 3 beta-HSD activity staining, and the number of 3 beta-HSD-positive cells were significantly decreased, indicating the ind uction of apoptotic cell death by PRL among luteal cells in culture. Next, the expression of membrane form-Fas ligand (mFasL) in the luteal cell lysat e was quantified, because Fas receptor is known to have an exact physiologi cal role in luteolysis. An addition of PRL increased the expression of mFas L. Immunostaining and TUNEL assay on regressing: CL revealed that both CD3- positive cells and FasL-positive cells were co-localized in the regions whe re apoptosis convergently occurred. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, to the culture mimicked the PRL actio n by inducing apoptosis in luteal cells and enhancing the expression of mFa sL. These data suggest that the CD3-positive T lymphocyte in the CL is at l east one of the PRL-effector cell species during the process of luteolysis in rats, and that Fast expression of these cells is upregulated by PRL. (C) 1999 Academic Press.