Tumor necrosis factor alpha alters follicular steroidogenesis in vitro

Preovulatory follicles from cyclic proestrous rats were incubated in vitro in M199 for up to 24 hours with various doses of human tumor necrosis factor alpha (TNF). Stepwise increases in progesterone (P) production (20-80 ng/ml/2 follicle/24 hours) were observed with 30-300 pM TNF; 3000 pM TNF reduced (p less than 0.001) P production compared to 300 pM TNF but it was still higher (p less than 0.001) than controls. Follicular androstenedione production was inhibited by low doses of TNF (30-60 pM TNF) and stimulated by 3000 pM TNF. TNF did not alter follicular estradiol (E2) production. The time course studies using 300 pM TNF revealed that follicular P production did not increase significantly until 24 hours in culture unlike LH (160 pM) which increased P by 6 hours. Preincubation of 30 pM TNF with a monoclonal antibody to human recombinant TNF alpha prevented the increase in follicular P production observed at 24 hours in TNF-treated controls. These results indicate that in vitro TNF stimulates follicular P production but only after a lag period and thus provide a basis for future studies elucidating the role of TNF in follicular development.