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 is an inducer of apoptotic cell death in luteal cells. This luteolytic action 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-induced apoptosis. Corpora lutea (CL) were prepared from the ovary on the proestrous day and cultured with or without PRL (2 microg/ml). An addition of PRL to the culture medium induced DNA breakdown in the nuclei of cells mostly identified as steroidogenic by 3beta-HSD activity staining, and the number of 3beta-HSD-positive cells were significantly decreased, indicating the induction of apoptotic cell death by PRL among luteal cells in culture. Next, the expression of membrane form-Fas ligand (mFasL) in the luteal cell lysate was quantified, because Fas receptor is known to have an exact physiological role in luteolysis. An addition of PRL increased the expression of mFasL. Immunostaining and TUNEL assay on regressing CL revealed that both CD3-positive cells and FasL-positive cells were co-localized in the regions where apoptosis convergently occurred. Moreover, an addition of concanavalin A (ConA), a T-cell specific activator, to the culture mimicked the PRL action by inducing apoptosis in luteal cells and enhancing the expression of mFasL. These data suggest that the CD3-positive T lymphocyte in the CL is at least one of the PRL-effector cell species during the process of luteolysis in rats, and that FasL expression of these cells is upregulated by PRL.
Kuranaga
E
E
Department of Veterinary Physiology, Veterinary Medical Science, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Kanuka
H
H
Bannai
M
M
Suzuki
M
M
Nishihara
M
M
Takahashi
M
M
D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000032:analysis; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003338:Corpus Luteum / Q000187:drug effects* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D005260:Female; D020287:In Situ Nick-End Labeling; D008562:Membrane Glycoproteins / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D011388:Prolactin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor; D013997:Time Factors; D019014:fas Receptor
D017252:CD3 Complex; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D009479:Neuropeptides; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D003208:Concanavalin A; D011388:Prolactin