INTERLEUKIN-6 PRODUCTION BY RAT GRANULOSA-CELLS INVITRO - EFFECTS OF CYTOKINES, FOLLICLE-STIMULATING-HORMONE, AND CYCLIC 3',5'-ADENOSINE-MONOPHOSPHATE

In the present study we examined the influence of FSH as well as a num ber of well-established cytokines on interleukin (IL)-6 by rat granulo sa cells in culture. Increasing concentrations of FSH, IL-1alpha, IL-1 beta, tumor necrosis factor alpha (TNFalpha), and lipopolysaccharide ( LPS) were incubated for 48 h with undifferentiated granulosa cells obt ained from diethylstilbestrol-primed immature rats. The results demons trate that FSH, IL-1alpha, IL-1beta, and LPS, but not TNFalpha, caused significant concentration-dependent increases in IL-6 release. We als o examined the effects of dibutyryl-cAMP, forskolin, and 3-isobutyl-1- methyl-xanthine (IBMX) on IL-6 release by granulosa cells. Each of the se agents caused a significant concentration-dependent increase in IL- 6 production by granulosa cells in either the absence or presence of F SH. Taken together, these results show that the granulosa cell is not only a likely source of IL-6 but that the release of IL-6 can be regul ated. Moreover, evidence suggests that cAMP may serve as a second mess enger for the stimulated secretion of IL-6 by undifferentiated granulo sa cells.