Interleukin-3 and interleukin-6 stimulate cortisol secretion from adult human adrenocortical cells
Abstract
Accumulating data indicate that interleukins can activate the hypothalamic-pituitary-adrenal (HPA) axis. We evaluated the effect of human recombinant interleukin-3 (IL-3) and interleukin-6 (IL-6) on cortisol secretion from adult human adrenocortical cells in primary culture. IL-3 and IL-6 (100 microg/L) equipotently stimulated basal cortisol secretion approximately 5-fold. The stimulatory effect was significant after 12 h (p<0.01) and maximum cortisol levels were induced after 48 h. In contrast to ACTH, which significantly induced cAMP levels in parallel to its steroidogenic effect, IL-3 or IL-6 had no significant effect on cAMP. Furthermore, we showed that specific inhibition of the cyclooxygenase pathway by indomethacin completely blocked the steroidogenic effect of IL-6 while the effect of IL-3 was not affected. In contrast, coincubation with nordihydroguaiaretic acid--a specific inhibitor of the lipoxygenase system--abolished IL-3 stimulated steroidogenesis but had no effect on IL-6 stimulated cortisol secretion. These findings indicate that IL-3 and IL-6 directly stimulate the steroidogenesis at the adrenal level through activation of different, cAMP-independent pathways. While the stimulatory effect of IL-6 on cortisol secretion from adult human adrenocortical cells seems to be mediated through the cyclooxygenase pathway, the effect of IL-3 on adrenocortical cortisol secretion is dependent on the lipoxygenase pathway.
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Corticotropin releasing hormone secreted by the hypothalamus increases ACTH secretion by the pituitary gland and may act directly on adrenocortical cells to increase cortisol secretion and expression of CYP21A2 and other steroidogenic enzymes.
“The main effect of corticotropin releasing hormone (CRH) secreted by the hypothalamus is to increase ACTH secretion by the pituitary gland, but additionally, it may act directly on adrenocortical cells to increase cortisol secretion, and expression of CYP21A2 and other steroidogenic enzymes (163).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [163]
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ИНТЕРЛЕЙКИН-6 И ДИАБЕТИЧЕСКАЯ НЕФРОПАТИЯ: ПАТОГЕНЕТИЧЕСКИЕ СВЯЗИ, МИШЕНИ ДЛЯ НЕФРОПРОТЕКЦИИ
Pchelin, I. Y., Байрашева, В. К., Шишкин, А. Н., Vasilkova, V., & Худякова, Н. В. (2017) · Juvenis scientia
- Authors
- Weber, M. M., Michl, P., Auernhammer, C. J., & Engelhardt, D.
- Affiliations
- LMU Klinikum (DE)
- Corresponding author
- Weber, M. M.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1997-05-01
- Volume
- 138
- Issue
- 5
- Pages
- 2207-2210
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2038220228
- Cited by
- 74
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 4 · 2020: 1 · 2019: 1 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 1
- FWCI
- 5.36
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- interleukin-3, interleukin-6, cortisol secretion, adrenocortical cells, steroidogenesis, hypothalamic-pituitary-adrenal axis, cyclooxygenase pathway, lipoxygenase pathway, cAMP-independent signaling, indomethacin, nordihydroguaiaretic acid, ACTH
- MeSH terms
- Cyclic AMP, Adrenal Cortex, Adrenocorticotropic Hormone, Adult, Cells, Cultured, Humans, Hydrocortisone, Indomethacin, Interleukin-3, Kinetics, Masoprocol, Recombinant Proteins, Interleukin-6, Lipoxygenase Inhibitors, Cyclooxygenase Inhibitors
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