Dehydroepiandrosterone (DHEA): A Steroid with Multiple Effects. Is there Any Possible Option in the Treatment of Critical illness?

Oberbeck, Reiner; Kobbe, Philipp

doi:10.2174/092986710790820570

Cited by 25 publications

(19 citation statements)

References 111 publications

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“…4 and 5, contributes to a decrease in fat mass and prevention of senescence. Epidemiological and clinical studies suggest that a high plasma DHEA-S level is associated with longevity (8,12,34,41); hence, our result supports the notion that DHEA prevents senescenceassociated phenomenon.…”

Section: Discussionsupporting

confidence: 87%

Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor

Fujioka¹,

Kajita²,

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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Several studies have suggested that both testosterone and dehydroepiandrosterone (DHEA) have weight-reducing and antidiabetic effects, especially in rodent studies; however, the precise mechanism of their action remains unclear. Here, we investigated the effect of DHEA on cell growth in adipose tissue. The appearance of senescence-associated β-galactosidase in stromal vascular fraction (SVF) isolated from Otsuka Long-Evans Tokushima fatty rats, an animal model of inherent obese type 2 diabetes, was prevented by DHEA administration. Next, the effects of DHEA and testosterone were compared in vivo and in vitro to evaluate whether these hormones influence cell growth in adipose tissue. Both DHEA and testosterone reduced body weight and epididymal fat weight equivalently when administered for 4 wk. To assess the effect of DHEA and testosterone on cell growth in adipose tissue, 5-bromo-2'-deoxyuridine (BrdU) uptake by SVF was measured. Quantification analysis of BrdU uptake by examining DNA isolated from each SVF revealed that treatment with DHEA and testosterone reduced cell replication. These results indicated that DHEA- and testosterone-induced decreased adiposity was associated with reduced SVF growth. Incubation with DHEA and testosterone equally decreased BrdU uptake by 3T3-L1 preadipocytes. Pretreatment with the androgen receptor (AR) inhibitor flutamide, but not the estrogen receptor inhibitor fulvestrant, abolished these effects. Knockdown of AR with siRNA also inhibited DHEA-induced decreases in BrdU uptake. These results suggest that DHEA-induced growth suppression of preadipocytes is mediated via AR. Therefore, both DHEA and testosterone similarly decrease adipocyte growth possibly via a common mechanism.

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Section: Discussionsupporting

confidence: 87%

Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor

Fujioka¹,

Kajita²,

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…Together, these findings indicate that maternal stress can program the development of the fetal adrenal gland so that there is diminished adrenal production of DHEA and preferential synthesis and secretion of cortisol. Such change of steroidogenesis also occurs in human patients with acute physiologic stress, such as burns (Lephart et al 1987), serious illnesses (Carlström et al 1990, Oberbeck & Kobbe 2010, and schizophrenia (Ritsner et al 2004). Interestingly, testosterone and androstenedione concentrations have also been observed to decline in men exposed to burn trauma, while cortisol concentrations were elevated (Dolecek 1989).…”

Section: Discussionmentioning

confidence: 96%

Adrenal steroidogenesis following prenatal dexamethasone exposure in the spiny mouse

Quinn¹,

Ratnayake²,

Castillo‐Melendez³

et al. 2014

Journal of Endocrinology

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Antenatal stress disturbs the development of the fetal hypothalamic-pituitary-adrenal axis and adrenal steroidogenesis. We investigated the effect of brief maternal exposure to high glucocorticoids (dexamethasone (DEX)) at mid-and late-pregnancy on adrenal structure and production of steroids in spiny mouse. Pregnant spiny mice were treated for 60 h with 125 mg/kg DEX or saline s.c. by osmotic minipump at day 20 (0.5) or 30 (0.75) of gestation. Immunohistochemical expression of steroidogenic acute regulatory-protein (StAR), 3b-hydroxysteroid dehydrogenase (3bHSD), 17-hydroxylase,17-20lyase (P450C17), and cytochromeb5 (CYTB5) was determined in adrenals on postnatal (P) day 170G20. DHEA, testosterone, and cortisol were measured by RIA. Maternal DEX at 20 days significantly reduced the expression of STAR, P450C17 (CYP17A1), and CYTB5 in the adrenal zona reticularis (ZR) of adult offspring, with greater change in male vs female offspring (P!0.05). Plasma DHEA was decreased in male offspring from DEX-treated (6.84G1.24 ng/ml) vs saline-treated (13G0.06 ng/ml; PZ0.01) dams, and the DHEA:cortisol ratio was lower in males (P!0.05). Testosterone levels increased in male offspring from DEX (266.03G50.75 pg/ml) vs saline (83.47G32.3 pg/ml, P!0.05)-treated dams. DEX treatment at 0.75 gestation had no significant effect on any parameters measured. This study shows that brief exposure to excess glucocorticoid has long-term impacts on the ZR and adrenal steroidogenesis, affecting the secretion of DHEA and testosterone in male offspring, an effect produced at 0.5 but not at 0.75 gestation. DHEA is important for brain development, and its suppression in adult life might contribute to the neurobehavioral pathologies that can arise after illness and stress during pregnancy.

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“…The physiological role of DHEA is poorly understood, but there are clear indications that it modulates the immune response and influences both pro-and anti-inflammatory cytokine release (51)(52)(53)(54).…”

Section: Discussionmentioning

confidence: 99%

Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

et al. 2015

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bHuman brucellosis is a protean disease with a diversity of clinical signs and symptoms resulting from infection with Brucella species. Recent reports suggest a cross-regulation between adrenal steroids (cortisol and dehydroepiandrosterone [DHEA]) and the immune system. Monocytes and macrophages are the main replication niche for Brucella. Therefore, we investigated the role of adrenal hormones on the modulation of the immune response mediated by macrophages in B. abortus infection. Cortisol treatment during B. abortus infection significantly inhibits cytokine, chemokine, and MMP-9 secretion. In contrast, DHEA treatment had no effect. However, DHEA treatment increases the expression of costimulatory molecules (CD40, CD86), the adhesion molecule CD54, and major histocompatibility complex class I (MHC- Human brucellosis is characterized by a great diversity of clinical manifestations resulting from infection with Brucella species (4). It is chiefly an inflammatory disease. Inflammation is present both in the acute and chronic phases of the disease and in practically all of the organs affected. Clinical signs of such inflammation are undulant fever, endocarditis, arthritis, osteomyelitis, meningitis, pleocytosis, cellular infiltration of the joints, orchitis, nephritis, hepatic granuloma, etc. (5).IBrucella abortus infection elicits a vigorous Th1 immune response, which also activates cytotoxic T lymphocytes (6-9). Despite the recognition that Th1 immunity is crucial for the control of Brucella infection, several aspects of the immune response, i.e., how the innate immune response shapes the adaptive Th1 immune response and why Th1 immunity is not sufficient to completely eradicate the infection, constitute a conundrum. Macrophages/monocytes were recognized to play an important role in resistance to facultative intracellular bacteria such as Brucella, and activation of macrophages by specifically committed T lymphocytes formed the basis for cell-mediated immunity. However, B. abortus is endowed with a panoply of survival stratagems to evade immune responses and survive inside macrophages, creating a safe niche of replication inside the host (10-13).Several cytokines that are produced during B. abortus infec- [18][19][20]. In previous studies, significantly higher levels of cortisol in serum were reported in patients with acute brucellosis than in brucellosis patients at the end of antibiotic treatment or than in healthy subjects (21). In addition, adrenal glands are enlarged in patients with acute brucellosis but return to normal size after therapy (21). Of note, Th1 Citation Gentilini MV, Velásquez LN, Barrionuevo P, Arriola Benitez PC, Giambartolomei GH, Delpino MV. 2015. Adrenal steroids modulate the immune response during Brucella abortus infection by a mechanism that depends on the regulation of cytokine production.

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Dehydroepiandrosterone (DHEA): A Steroid with Multiple Effects. Is there Any Possible Option in the Treatment of Critical illness?

Cited by 25 publications

References 111 publications

Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor

Dehydroepiandrosterone reduces preadipocyte proliferation via androgen receptor

Adrenal steroidogenesis following prenatal dexamethasone exposure in the spiny mouse

Adrenal Steroids Modulate the Immune Response during Brucella abortus Infection by a Mechanism That Depends on the Regulation of Cytokine Production

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