P. Michl et al., Interleukin-3 and interleukin-6 stimulate bovine adrenal cortisol secretion through different pathways, J NEUROENDO, 12(1), 2000, pp. 23-28
Several interleukins have been reported to play a major role in the regulat
ion of steroid secretion at all three levels of the hypothalamic-pituitary-
adrenal axis. The objective of this study was to investigate the effect of
interleukin-3 (IL-3) and interleukin-6 (IL-6) on cortisol secretion of bovi
ne adrenocortical cells in primary culture under serum-free conditions. Bot
h IL-3 and IL-6 stimulated basal cortisol secretion dose-dependently to a s
imilar extent at a similar time course. After incubation with IL-3 or IL-6
at concentrations of 100 mu g/l, a maximum 4.1-fold increase of the cortiso
l secretion was reached after 12 h (P < 0.01). Coincubation of IL-3 and IL-
6 (100 mu g/l) revealed no significant synergism. To elucidate a possible i
nvolvement of arachidonic acid metabolites in the signal transduction, we c
oincubated IL-3 or IL-6 together with the cyclo-oxygenase inhibitor indomet
acin or the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Coincu
bation with indometacin completely abolished the stimulatory effect of IL-6
but had no effect on IL-3 stimulated cortisol secretion. In contrast, spec
ific inhibition of the lipoxygenase system by nordihydroguaiaretic acid blo
cked IL-3 stimulated steroidogenesis while the effect of IL-6 was not affec
ted. Neither IL-3 nor IL-6 altered cAMP levels significantly, whereas ACTH
significantly induced cAMP levels in parallel to its steroidogenic effect.
In conclusion, our data indicate that IL-3 and IL-6 stimulate the steroid s
ecretion of bovine adrenocortical cells to a similar extent and with a simi
lar time course. However, the effects of IL-3 and IL-6 are mediated through
different, cAMP-independent pathways. While the stimulatory effect of IL-3
seems to be dependent on the lipoxygenase pathway, the effect of IL-6 on a
drenocortical cortisol secretion is mediated through the cyclo-oxygenase pa
thway.