EFFECTS OF CYTOKINES ON FSH-INDUCED ESTRADIOL PRODUCTION BY BOVINE GRANULOSA-CELLS IN-VITRO - DEPENDENCE ON SIZE OF FOLLICLE

The objective of the present studies was to determine the effect of cy tokines on FSH-induced estrogen production by granulosa cells from sma ll (1-5 mm) and large (greater than or equal to 8 mm) bovine follicles . FSH-induced estradiol production by granulosa cells from large folli cles (expressed as pg estradiol/l0(5) cells/24 hr) was not affected (P >.05) by 10 or 100 ng/ml of interleukin (IL)-1 beta, 10 or 100 ng/ml o f tumor necrosis factor-a (TNF alpha) or 100 ng/ml of IL-2. In contras t, 100 ng/ml of IL-1 beta, IL-2 or TNF alpha inhibited (P<.05) FSH-ind uced estradiol production by 31%, 55% or 72%, respectively in cells fr om small follicles. Interferon-a (IFN alpha; 100 U/ml) inhibited (P<.0 5) FSH-induced estradiol production by 61% and 20% in cultures of cell s from small and large follicles, respectively. Interferon-beta (IFN b eta; 100 U/ml), interferon gamma (IFN gamma; 100 U/ml) and bovine trop hoblast protein-1 (bTP-1; 100 U/ml) inhibited (P<.05) estradiol produc tion by 47%, 71% and 28%, respectively in cells from small follicles, but had no effect (P>.05) on FSH-induced estradiol production in cells from large follicles. TNF alpha binding protein-I blocked (P<.05) the inhibitory effect of TNF alpha on FSH-induced estradiol production by cells from small follicles. Viability of granulosa cells was not affe cted (P>.05) by the various cytokines. In summary, cytokines have litt le or no effect on FSH-induced estradiol production by bovine granulos a cells collected from large follicles, whereas cytokines (bTP-1 less than or equal to IL-1 beta < IL-2 = IFN beta < IFN alpha < IFN gamma = TNF alpha) have potent inhibitory effects on FSH-induced estradiol pr oduction by granulosa cells collected from small follicles. Thus, it a ppears that less differentiated granulosa cells (small follicles) are more responsive to cytokines than are highly differentiated granulosa cells (large follicles).