Tumor Necrosis Factor α: Localization and Actions Within the Preovulatory Follicle

Abstract

In 1985 we reported that the hamster ovary contained mast cells (1). This discovery led us to investigate the effects of histamine and serotonin on follicular and luteal function because these amines are the primary secretory products of mast cells. We extended our findings to the cow (2) and the human (3–4). Another major secretory product of mast cells is heparin, and it was evident from a previous study that heparin could synergize with fibroblast growth factor in promoting endothelial cell growth (5). Thus, we began our search in the ovary for growth factors that bind heparin. During the course of our studies, Gospodarowicz reported that the bovine corpus luteum contained FGF (6). During our purification scheme, using various concentrations of ammonium sulphate, we found a fraction that inhibited the growth of endothelial cells in vitro and reported this at the 1987 SSR meeting at Cornell. Subsequently, we published a full description of our findings (7–8). It was at this point that we asked the question: What ovarian factor might retard the growth of endothelial cells in vitro? In searching the literature we found a publication by Sato, et al., 1986, that described morphological changes in the endothelial cells treated with tumor necrosis factor alpha (TFNα) (9). Thus, with the assistance of Genentech, Inc., we secured monoclonal and polyclonal antibodies to human recombinant TNFα and embarked on our studies elucidating the presence of TNF in the ovary of the rat, human, and cow. The following discussion of the pertinent literature on TNF in the ovary describes its presence in specific ovarian compartments and its effects on ovarian function in vitro.