Role of tumor necrosis factor or and its type I receptor in luteal regression: Induction of programmed cell death in bovine corpus luteum-derived endothelial cells

The role of tumor necrosis factor or (TNF alpha) and its type I receptor (T NFRI) in structural luteolysis was investigated; A semiquatitative reverse- transcription polymerase chain reaction (RT-PCR) was used to characterize t he pattern of TNFRI mRNA expression within the corpus luteum (CL) throughou t the estrous cycle and its cellular distribution. Increase in TNFRI mRNA l evels was recorded both in regressed luteal tissue and in CL of cows inject ed with prostaglandin F-2 alpha. All three major cell types composing the C t, steroidogenic (large and small) and endothelial cells expressed the TNFR I gene. A densitometric analysis of TNFRI mRNA expression revealed that res ident endothelial cells had significantly higher levels of TNFRI mRNA than steroidogenic luteal cells. The physiological effects associated with TNFRI expression were investigated in the various luteal cell types. TNF alpha - induced programmed cell death (PCD) in dose- and time-dependent manners of cultured luteal endothelial cells (LECs) but not of in vitro luteinized ste roidogenic cells. Several lines of evidence are provided to show that proge sterone regulates luteal cell survival: 1) CL and LECs express progesterone receptor mRNA, 2) physiological levels of the steroid abolished TNF alpha -induced PCD of LECs, and 3) progesterone-producing cells are protected fro m PCD. In conclusion, this study suggests that TNFa-induced PCD during stru ctural luteolysis is mediated by TNFRI, primarily affects endothelial cells , and that the decline in progesterone, preceding structural luteolysis, is a prerequisite for the initiation of apoptosis in endothelial cells.