Physiological Levels of 5α-Dihydrotestosterone Depress Wound Immune Function and Impair Wound Healing Following Trauma-Hemorrhage

Nitsch, S.; Wittmann, F; Angele, Peter; Wichmann, Matthias W.; Hatz, Rudolf; Hernandez-Richter, T.; Chaudry, Irshad H.; Jauch, Karl Walter; Angele, Martin K.

doi:10.1001/archsurg.139.2.157

Cited by 18 publications

(8 citation statements)

References 32 publications

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“…To study this, male mice were castrated 2 wk before trauma-hemorrhage or sham operation. In several previous studies, castration of male mice 2 wk before the experiment has been shown to significantly lower plasma testosterone levels by ϳ95% (2,6,26,39). This reduction in testosterone plasma levels after castration was comparable in all studies (2, 6, 26, 39).…”

Section: Discussionsupporting

confidence: 54%

Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage

Mayr¹,

Walz²,

Angele³

et al. 2006

Journal of Applied Physiology

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. Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage. J Appl Physiol 101: 448 -453, 2006. First published April 13, 2006; doi:10.1152 doi:10. /japplphysiol.00166.2006eral studies indicate that cell-mediated immune responses, i.e., macrophage (M⌽) cytokine release capacities, myosin heavy chain (MHC) class II (Ia) expression, etc., are suppressed after traumahemorrhage in male mice. Testosterone has been shown to be responsible for the depression of M⌽ cytokine responses in males after trauma-hemorrhage. Antigen presentation via MHC class II plays a key role in initiating and maintaining cell-mediated and humoral immune responses. It remains unknown, however, whether testosterone has any effect on MHC class II after trauma-hemorrhage. To study this, male C3H/HeN mice were castrated or sham castrated 2 wk before trauma (midline laparotomy) and hemorrhage (Hem; blood pressure 35 Ϯ 5 mmHg for 90 min and resuscitation) or sham operation. Four hours thereafter, MHC class II (Ia) expression was measured using flow cytometry. The results indicate that MHC class II (Ia) expression on peritoneal and splenic M⌽ was significantly suppressed in male mice after trauma-hemorrhage. Prior castration, however, prevented the depression in MHC class II (Ia) expression on peritoneal and splenic M⌽ after trauma-hemorrhage. Castration did not affect MHC class II (Ia) expression in M⌽ from sham-castrated mice. Thus testosterone depresses MHC class II (Ia) expression on peritoneal and splenic M⌽ after trauma-hemorrhage in males. Because MHC class II is necessary for an adequate immune response, our results suggest that depletion of male sex steroids or blockade of androgen receptors using agents such as flutamide might prevent immunosuppression via maintaining MHC class II (Ia) expression after trauma and severe blood loss. antigen presentation; immunosuppression

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Section: Discussionsupporting

confidence: 54%

Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage

Mayr¹,

Walz²,

Angele³

et al. 2006

Journal of Applied Physiology

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“…The rationale for also testing 5a-DHT and 17b-estradiol were established by previous reports on the negative and positive influences, respectively, of these natural hormonal signals on skin [12,[20][21][22][23]. This study demonstrates equol's interaction with 5a-DHT that showed this botanical molecule can restore dermal cell viability and influence the expression of ECM components in a positive manner similar to that of the natural chemical messenger, 17b-estradiol, an estrogenic steroid compound known for its topical benefits on ECM proteins [12,22,23].…”

Section: Discussionmentioning

confidence: 99%

“…Equol is also a selective androgen modulator, having the ability to specifically bind 5a-dihydrotestosterone (5a-DHT) and inhibit its potent actions in skin [19]. For example, it is known that androgens decrease skin health (increase MMPs and decrease wound healing), whereas estrogens are known to have positive influences on the skin aging process (e.g., increase collagen, elastin (ELN), and decrease MMPs) [12,[20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Biochemical investigation and gene analysis of equol: A plant and soy‐derived isoflavonoid with antiaging and antioxidant properties with potential human skin applications

2012

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The purpose of this study was to investigate the effects of equol, a plant and intestinal flora derived isoflavonoid molecule on the expression of skin genes and proteins using human dermal models. As equol has been shown to mimic 17β-estradiol and bind specifically to 5α-dihydrotestostone (5α-DHT), these agents were used (in addition to equol) to determine whether equol may play important and beneficial roles in the extracellular matrix (ECM). Equol at 0.3 or 1.2% in qPCR experiments using a human skin barrier model examined ECM gene expression. Equol, 5α-DHT, and 17β-estradiol at 10 nM were studied in human monolayer fibroblasts cultures (hMFC) for ECM protein expression. Human fibroblast three-dimensional organotypic cultures revealed equol's influence (@ 10 nM) on ECM proteins via fluorescent-activated cell sorting (FACS) analysis. In qPCR experiments, equol significantly increased collagen, elastin (ELN), and tissue inhibitor of metalloprotease and decreased metalloproteinases (MMPs) gene expression and caused significant positive changes in skin antioxidant and antiaging genes. In hMFC, equol significantly increased collagen type I (COL1A1), whereas, 5α-DHT significantly decreased cell viability that was blocked by equol. FACS analysis showed equol and 17β-estradiol significantly stimulated COL1A1, collagen type III (COL3A1), and ELN while MMPs were significantly decreased compared with control values. Finally, tamoxifen blocked the positive influences of equol on ECM proteins via FACS analysis. These findings suggest that equol has the potential to be used topically for the treatment and prevention of skin aging, by enhancing ECM components in human skin.

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“…Others seemingly do not: both testosterone and DHT were shown to increase macrophage expression of IL-6 mRNA [168]. Castration was previously found to protect against potentially harmful wound induction of the same cytokine in mice subjected to traumahemorrhage [171].…”

Section: Androgensmentioning

confidence: 99%

Sex steroids as inflammatory regulators

Gilliver¹

2010

The Journal of Steroid Biochemistry and Molecular Biology

171

127

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Physiological Levels of 5α-Dihydrotestosterone Depress Wound Immune Function and Impair Wound Healing Following Trauma-Hemorrhage

Cited by 18 publications

References 32 publications

Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage

Castration prevents suppression of MHC class II (Ia) expression on macrophages after trauma-hemorrhage

Biochemical investigation and gene analysis of equol: A plant and soy‐derived isoflavonoid with antiaging and antioxidant properties with potential human skin applications

Sex steroids as inflammatory regulators

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