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Interleukin‐3 and Interleukin‐6 Stimulate Bovine Adrenal Cortisol Secretion Through Different Pathways
Author(s) -
Michl,
Beikler,
Engelhardt,
; Weber
Publication year - 2000
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1046/j.1365-2826.2000.00423.x
Subject(s) - nordihydroguaiaretic acid , medicine , endocrinology , lipoxygenase , secretion , arachidonic acid , interleukin , biology , cytokine , chemistry , enzyme , biochemistry
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 μg/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 μg/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.