Lipopolysaccharide Directly Stimulates Cortisol Secretion by Human Adrenal Cells by a Cyclooxygenase-Dependent Mechanism

Vakharia, Kunal; Hinson, J. P.

doi:10.1210/en.2004-0882

Cited by 87 publications

(57 citation statements)

References 26 publications

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“…Surprisingly, and partially in contrast to previous studies in adrenocortical cell cultures in vitro that have implicated TLR-signaling in the regulation of steroidogenesis (20), this study revealed no contribution of adrenocortical MyD88 to the systemic HPA activation or to the local immune-adrenal cross talk within the adrenal microenvironment in LPS-induced inflammation. On the other hand, our findings with these Mx1…”

Section: Discussioncontrasting

confidence: 99%

Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation

Kanczkowski

Alexaki

Tran

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Inflammation-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is central to the course of systemic inflammatory response syndrome or sepsis. The underlying mechanisms, however, are not well understood. Initial activation of adrenocortical hormone production during early sepsis depends on the stimulation of hypothalamus and pituitary mediated by cytokines; in late sepsis, there is a shift from neuroendocrine to local immuneadrenal regulation of glucocorticoid production. Therefore, the modulation of the local immune-adrenal cross talk, and not of the neuroendocrine circuits involved in adrenocorticotropic hormone production, may be more promising in the prevention of the adrenal insufficiency associated with prolonged sepsis. In the present work, we investigated the function of the crucial Toll-like receptor (TLR) adaptor protein myeloid differentiation factor 88 (MyD88) in systemic and local activation of adrenal gland inflammation and glucocorticoid production mediated by lipopolysachharides (LPSs). To this end, we used mice with a conditional MyD88 allele. These mice either were interbred with Mx1 Cre mice, resulting in systemic MyD88 deletion, predominantly in the liver and hematopoietic system, or were crossed with Akr1b7 Cre transgenic mice, resulting thereby in deletion of MyD88, which was adrenocortical-specific. Although reduced adrenal inflammation and HPAaxis activation mediated by LPS were found in Mx1Cre+ -MyD88 fl/fl mice, adrenocortical-specific MyD88 deletion did not alter the adrenal inflammation or HPA-axis activity under systemic inflammatory response syndrome conditions. Thus, our data suggest an important role of immune cell rather than adrenocortical MyD88 for adrenal inflammation and HPA-axis activation mediated by LPS.adrenal gland insufficiency | Toll-like receptors | the HPA axis S epsis and septic shock are major causes of death in intensivecare units worldwide and show an increasing incidence (1). In sepsis, excessive, uncontrolled activation of the immune system is harmful to the host and leads to multiorgan failure and death. Adrenal glucocorticoid production plays a beneficial role in response to systemic inflammation by counteracting hyperactivation of the immune system. However, in many critically ill patients, this homeostatic activation of adrenocortical hormone secretion is impaired (2). It has been estimated that 60% of critically ill patients show an abnormal adrenal glucocorticoid response to administration of exogenous adrenocorticotropic hormone (ACTH) (3).Adrenal hormone production in sepsis is thought to be regulated by cytokines that elevate hypothalamic corticotropin releasing hormone (CRH) levels. CRH, in turn, produces the release of pituitary ACTH-the main regulator of synthesis of adrenal glucocorticoid hormones (4). It is generally accepted that patternrecognition receptors such as Toll-like receptors (TLRs) play a substantial role in hypothalamic-pituitary-adrenal (HPA) axis activation induced by pathogens. This activation, in turn, may be a...

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Section: Discussioncontrasting

confidence: 99%

Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation

Kanczkowski

Alexaki

Tran

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…TLR4 is expressed on human adrenocortical cells, and it is involved in immuneneuroendocrine crosstalk (Zacharowski et al, 2006). LPS directly stimulates cortisol secretion by NCI-H295 cells (Vakharia and Hinson, 2005), and IL-6 and IL-8 expression by human adrenocortical cells (Kanczkowski et al, 2009). We found significant underexpression of TLR4 in ACCs in two studies (Giordano et al, 2009;To¨mbo¨l et al, 2009) and confirmed TLR4 expression changes by QRT-PCR (data not shown).…”

Section: Bacterial Lipopolysaccharide (Lps) Recognition Via Toll-likesupporting

confidence: 80%

Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

et al. 2010

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“…Both fatty acids have been found to be good precursors of cyclooxygenase-derived PG in fish (Bell et al 1994a, Ganga et al 2005. In turn, cyclooxygenase-derived PG have been shown to increase in vitro cortisol release in interrenal tissue of female frogs during ovulation (Gobbetti & Zerani 1993) and in human adrenal cells as well (Vakharia & Hinson 2005). Interestingly, DHA stimulation of ACTH-induced cortisol production was lower than that caused by EPA or ARA.…”

Section: Discussionmentioning

confidence: 99%

Modulation of ACTH-induced cortisol release by polyunsaturated fatty acids in interrenal cells from gilthead seabream, Sparus aurata

Ganga¹,

Tort²,

Acerete³

et al. 2006

Journal of Endocrinology

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Highly unsaturated fatty acids are essential components of cellular membranes of vertebrates and can modulate physiological processes, including membrane transport, receptor function and enzymatic activities. In gilthead sea bream, dietary deficiencies of essential fatty acids of marine fish raise the basal cortisol levels and alter the pattern of cortisol release after stress. The aim of the present study was to clarify the effect of different essential fatty acids on adrenocorticotropic hormone (ACTH)-induced cortisol production and release in fish, through in vitro studies of sea bream interrenal cells maintained in superfusion and incubated with different types of fatty acids and eicosanoid production inhibitors. Results showed the first evidence of the effect of certain fatty acids on cortisol production by ACTH-stimulated interrenal cells in fish. Both arachidonic acid (ARA) and particularly eicosapentaenoic acid (EPA) promoted cortisol production in sea bream interrenal cells. Moreover, incubation with indometacin (INDO) reduced the increased cortisol production induced by EPA and ARA, suggesting mediation by their cyclooxygenase-derived products. Docosahexaenoic acid stimulated cortisol production to a lesser extent than that caused by EPA or ARA, but the inhibitory effect of INDO was not as marked as it was for the other fatty acids. In contrast, supplementation with dihomogammalinoleic acid reduced cortisol production, denoting the inhibitor effect of this fatty acid in cortisol secretion.

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Lipopolysaccharide Directly Stimulates Cortisol Secretion by Human Adrenal Cells by a Cyclooxygenase-Dependent Mechanism

Cited by 87 publications

References 26 publications

Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation

Hypothalamo-pituitary and immune-dependent adrenal regulation during systemic inflammation

Meta-analysis of adrenocortical tumour genomics data: novel pathogenic pathways revealed

Modulation of ACTH-induced cortisol release by polyunsaturated fatty acids in interrenal cells from gilthead seabream, Sparus aurata

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