REVIEW - CYTOKINE INVOLVEMENT IN OVARIAN PROCESSES

PROBLEM: Expression of tumor necrosis factor-alpha (TNF) and interleuk ins 1 alpha and 1 beta (IL-1) have been reported in ovaries of several species and humans and are implicated in ovarian follicular developme nt and atresia, ovulation, steroidogenesis, and corpus luteum function (including formation, development, and regression). The principal abn ormal processes affected by these cytokines are ovarian cancer and red uction of ovarian function during sepsis. METHODS: A literature review . RESULTS: Numerous studies indicate that TNF and IL-1 inhibit gonadot ropin-stimulated steroidogenesis of undifferentiated ovarian cells due to inhibition of adenylyl cyclase and post-cAMP sites. In differentia ted ovarian cells, these cytokines either stimulate progesterone synth esis or have little to no effect on steroidogenesis. Both cytokines pa rticipate in ovulation and levels of these cytokines increase during t he periovulatory period. Endotoxin inhibits gonadotropin-stimulated ov arian steroidogenesis and follicular development and these effects are mediated, in part, by TNF and by direct effects of endotoxin on ovari an cells. In newly formed corpora lutea, progesterone secretion is inh ibited by TNF and IL-1, although each has proliferative effects. TNF a lso has been implicated in regression of corpora lutea because TNF sti mulates prostaglandin synthesis and luteal TNF increases after initiat ion of the decline in progesterone secretion. TNF and IL-1 are secrete d by some ovarian cancer cells and stimulate growth of these cells. CO NCLUSIONS: Thus, TNF and IL-1 are multifunctional factors affecting va rious ovarian processes.