TNF α: Altering Thecal and Granulosal Cell Steroidogenesis

Tumor necrosis factor α (TNF α) is a 17-kDa protein produced by macrophages in response to lipopolysaccharide (LPS) (1). Recent studies indicate that the ovary contains and produces TNF α (2-6). TNF α has been localized immunohistochemically in the ovary of the rat, cow (3), and human (4), and it has been detected in the human ovary by a bioassay specific for TNF α (5). Granulosa cells are a source of ovarian TNF α based on the presence of immunoreactive TNF α in cultured cells (3,4) and media (4,5) and in frozen ovarian sections (3,4). TNF α also has been shown to alter ovarian steroidogenesis (7-11). Using granulosa cells from the DES-treated immature rat (8, 9,11,12) and the adult rat (10), several labs have shown that TNF α inhibits FSH-stimulated progesterone production. In addition, our laboratory has found that TNF α stimulates thecal progestin production in adult rat preovulatory follicles (10). The purpose of this chapter is to review the current literature on TNF α in the ovary and attempt to construct a hypothesis as to the role(s) of TNF α in ovarian function.