A stimulatory effect of interleukin-1 on adrenocortical cortisol secretion mediated by prostaglandins
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Published on: March 2, 2011
J S Winter1, K W Gow, Y S Perry
1Department of Pediatrics, University of Manitoba, Winnipeg, Canada.
Insights
Interleukin-1 (IL-1) stimulates cortisol secretion in bovine adrenal cells indirectly through prostaglandin release, despite lacking detectable IL-1 receptors. This cytokine-mediated pathway offers new insights into adrenal gland regulation.
Area of Science:
- Endocrinology
- Cell Biology
- Immunology
Background:
- Interleukin-1 (IL-1) is a cytokine involved in immune responses.
- The role of IL-1 in adrenal steroidogenesis is not fully understood.
- Previous studies had conflicting results regarding IL-1's effect on cortisol secretion.
Purpose of the Study:
- To investigate the direct and indirect effects of IL-1 on cortisol secretion in cultured bovine adrenocortical cells.
- To determine the presence of IL-1 receptors in adrenal cells.
- To elucidate the signaling pathway involved in IL-1-induced cortisol secretion.
Main Methods:
- Cultured bovine adrenocortical cells were treated with IL-1 alpha and IL-1 beta.
- IL-1 receptor binding assays were performed using iodinated IL-1 alpha.
- The effect of indomethacin on IL-1-induced cortisol secretion was assessed.
- Prostaglandin production was measured using [3H]arachidonate conversion assays.
Main Results:
- IL-1 alpha and IL-1 beta stimulated cortisol secretion in a dose- and time-dependent manner.
- No detectable IL-1 receptors were found in adrenal cells.
- Indomethacin blocked the stimulatory effect of IL-1, suggesting prostaglandin mediation.
- IL-1 enhanced prostaglandin synthesis by adrenal cells.
- Specific prostaglandins (PGD2, PGF2 alpha, PGE2) stimulated cortisol production.
Conclusions:
- IL-1 stimulates cortisol secretion in bovine adrenal cells indirectly.
- The mechanism involves the local release of prostaglandins by adrenal cells.
- This pathway highlights a novel interaction between cytokines and the endocrine system in regulating cortisol production.
Abstract:
Studies using cultured bovine adrenocortical cells now demonstrate that the cytokines interleukin-1 (IL-1) alpha and beta, contrary to previous reports, can stimulate cortisol secretion in vitro in a dose- and time-dependent fashion. However detectable levels of IL-1 receptor could not be demonstrated in adrenal cortical, medullary, or capsular cells by membrane displacement of iodinated IL-1 alpha by unlabeled IL-1 beta, a technique that readily demonstrates specific IL-1 alpha-binding sites on 3T3 fibroblasts. The stimulatory effect of IL-1 on cortisol secretion could be totally blocked by indomethacin, an indication that this effect might be mediated indirectly via local release of prostaglandins (PGs). Subsequent investigations have confirmed that IL-1 does enhance the conversion of [3H]arachidonate to PGs by cultured adrenal cells, and that some of these PGs (PGD2, PGF2 alpha, and PGE2), in turn, can stimulate cortisol production. Taken together these observations suggest that IL-1-induced stimulation of cortisol secretion is mediated through local release of PGs by a small subpopulation of cells within the adrenal gland.
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