Interleukin-3 and interleukin-6 stimulate bovine adrenal cortisol secretion through different pathways.
Several interleukins have been reported to play a major role in the regulation 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 bovine adrenocortical cells in primary culture under serum-free conditions. Both IL-3 and IL-6 stimulated basal cortisol secretion dose-dependently to a similar extent at a similar time course. After incubation with IL-3 or IL-6 at concentrations of 100 microg/l, a maximum 4.1-fold increase of the cortisol secretion was reached after 12 h (P<0.01). Coincubation of IL-3 and IL-6 (100 microg/l) revealed no significant synergism. To elucidate a possible involvement of arachidonic acid metabolites in the signal transduction, we coincubated IL-3 or IL-6 together with the cyclo-oxygenase inhibitor indometacin or the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Coincubation with indometacin completely abolished the stimulatory effect of IL-6 but had no effect on IL-3 stimulated cortisol secretion. In contrast, specific inhibition of the lipoxygenase system by nordihydroguaiaretic acid blocked IL-3 stimulated steroidogenesis while the effect of IL-6 was not affected. 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 secretion of bovine adrenocortical cells to a similar extent and with a similar 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 adrenocortical cortisol secretion is mediated through the cyclo-oxygenase pathway.
Michl
P
P
Medical Department II, Laboratory of Endocrine Research, Klinikum Grosshadern, University of Munich, Munich, Germany.
Beikler
T
T
Engelhardt
D
D
Weber
M M
MM
D000302:Adrenal Cortex / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D015383:Zona Fasciculata / Q000187:drug effects / Q000502:physiology; D015385:Zona Reticularis / Q000187:drug effects / Q000502:physiology
D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D009637:Masoprocol; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D006854:Hydrocortisone; D007213:Indomethacin