Involvement of immune cells in regulation of ovarian function.
Primary cultures of luteal cells have been used to determine both acute and chronic effects of cytokines on luteal cell function and viability. Gonadotrophin-stimulated progesterone production is inhibited by interleukin 1 beta (IL-1 beta), tumour necrosis factor alpha (TNF-alpha), or gamma-interferon (IFN-gamma), the last two cytokine being more effective than IL-1. In contrast, all three cytokines are potent stimulators of prostaglandin production by these cells. The mechanism by which prostaglandin synthesis is enhanced may differ slightly for each cytokine. In luteal cells, TNF-alpha appears to act primarily through stimulation of phospholipase A2, whereas IL-1 beta may activate phospholipase C and prostaglandin endoperoxide synthase (PGS) in addition to phospholipase A2. The mechanism of action of IFN-gamma has not yet been determined. In addition to the observed functional effects, cytokines may also promote cell death during luteal regression. Although the three cytokines mentioned have little or no effect on viability of cultured luteal cells when administered separately, combined treatment with TNF-alpha and IFN-gamma results in a substantial decrease in the number of viable cells. Inhibition of cytokine-stimulated prostaglandin production does not alter the cytotoxic effect of these cytokines. Expression of major histocompatibility (MHC) class I molecules on luteal cells is enhanced, and MHC class II molecules are induced, by exposure to IFN-gamma. This is especially intriguing, as MHC class II expression increases before luteal regression in vivo, and is suppressed in early pregnancy. In summary, evidence is rapidly accumulating that supports the hypothesis that the function or structural integrity of luteal cells may be modulated by resident immune cells. Future research will probably address how these local events are hormonally controlled, and if they can be modified to regulate corpus luteum function.
Pate
J L
JL
Ohio State University, Department of Animal Sciences, Columbus 43210, USA.
D000818:Animals; D002417:Cattle; D003338:Corpus Luteum / Q000276:immunology*; D016207:Cytokines / Q000502:physiology*; D005260:Female; D003341:Luteolysis / Q000276:immunology*; D008214:Lymphocytes / Q000502:physiology*; D011374:Progesterone / Q000502:physiology; D012756:Sheep
D016207:Cytokines; D011374:Progesterone