Testosterone signaling in T cells and macrophages

Wunderlich, Frank; Benten, W. Peter M.; Lieberherr, Michèle; Guo, Zhiyong; Stamm, Olaf; Wrehlke, Christian; Sékeris, Constantin E.; Mossmann, Horst

doi:10.1016/s0039-128x(01)00175-1

Cited by 107 publications

(75 citation statements)

References 15 publications

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“…At a concentration of 10 nM, which is within the physiological range (21), testosterone significantly inhibits the production of nitrite, a metabolite of NO, from RAW 264.7 cells activated by exposure to lipopolysaccharide. By contrast, high doses of estrogen (22) increase nitrite production from these cells (Fig.…”

Section: Gender Differences On Renal Function and Morphology Aftermentioning

confidence: 93%

Testosterone Is Responsible for Enhanced Susceptibility of Males to Ischemic Renal Injury

Park

Kim

Ahn

et al. 2004

Journal of Biological Chemistry

292

273

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Female mice are much more resistant to ischemia/ reperfusion (I/R)-induced kidney injury when compared with males. Although estrogen administration can partially reduce kidney injury associated with I/R, we demonstrated that the presence of testosterone, more than the absence of estrogen, plays a critical role in gender differences in susceptibility of the kidney to ischemic injury. Testosterone administration to females increases kidney susceptibility to ischemia. Dihydrotestosterone, which can not be aromatized to estrogen, has effects equal to those of testosterone. Castration reduces the I/R-induced kidney injury. In contrast, ovariectomy does not affect kidney injury induced by ischemia in females. Testosterone reduces ischemia-induced activation of nitric oxide synthases (NOSs) and Akt and the ratio of extracellular signal related kinase (ERK) to c-jun N-terminal kinase (JNK) phosphorylation. Pharmacological (N -nitro-L-arginine) or genetic (endothelial NOS or inducible NOS) inhibition of NOSs in females enhances kidney susceptibility to ischemia. Nitric oxide increases Akt phosphorylation and protects MadinDarby canine kidney epithelial cells from oxidant stress. Antagonists of androgen or estrogen receptors do not affect the gender differences. In conclusion, testosterone inhibits the post-ischemic activation of NOSs and Akt and the ratio of ERK to JNK phosphorylation through non-androgen receptor-medicated mechanisms, leading to increased inflammation and increased functional injury to the kidney. These findings provide a new paradigm for the design of therapies for ischemia/ reperfusion injury and may be important to our understanding of the pathophysiology of acute renal failure in pregnancy where plasma androgen levels are elevated.

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Section: Gender Differences On Renal Function and Morphology Aftermentioning

confidence: 93%

Testosterone Is Responsible for Enhanced Susceptibility of Males to Ischemic Renal Injury

Park

Kim

Ahn

et al. 2004

Journal of Biological Chemistry

292

273

View full text Add to dashboard Cite

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“…For over two decades a group of researchers led by Frank Wunderlich have demonstrated [Ca 2+ ] i changes due to androgen treatment on a number of cell types including murine macrophages [29]. The macrophages used in these experiments lacked measurable expression of the intracellular AR.…”

Section: Androgens Can Interact With Intracellular Calcium Regulatorymentioning

confidence: 99%

Non-genomic actions of androgens

Foradori

Weiser

Handa

2008

Frontiers in Neuroendocrinology

397

244

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Previous work in the endocrine and neuroendocrine fields has viewed androgen receptors (AR) as a transcription factor activated by testosterone or one of its many metabolites. The bound androgen receptor acts as transcription factor and binds to specific DNA response elements in target gene promoters, causing activation or repression of transcription and subsequently protein synthesis. Over the past two decades evidence has begun to accumulate to implicate androgens, dependent or independent of the AR, in rapid actions at the cellular and organism level. Androgen's rapid time course of action; effects in the absence or inhibition of the cellular machinery necessary for transcription/translation; and/or the effects of androgens not able to translocate to the nucleus suggest a method of androgen action not initially dependent on genomic mechcanisms (i.e. non-genomic in nature). In the present paper the non-genomic effects of androgens are reviewed, along with a discussion of the possible role non-genomic androgen actions have on animal physiology and behavior.

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“…Previous studies has also documented that male sex hormone, testosterone plays an important role for infections with parasitic protozoans inducing an immuno-suppressive effect (Greenblatt, 1980;Alexander, 1988). Macrophages and lymphocytes, the two major cell types involved in the disease outcome of leishmaniasis, possesses receptors for sex hormones such as androgen, estrogens and progesterone (Wunderlich et al, 2002;Danel et al, 1983;Jones et al, 2008). Based on these data it is not surprising that testosterone could affect the outcomes of VL.…”

Section: Ajimentioning

confidence: 81%

Association of Testosterone and Cholesterol Level in Modulation of Immunity and Severity of Disease in Visceral Leishmaniasis Patients-a Preliminary Study

Pandey¹

2014

American Journal of Immunology

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Males are more prone to Visceral Leishmaniasis (VL) as compared to females. The role of androgens in host defence against Leishmania and other pathogens is of considerable interest. This study was aimed to understand a baseline mechanistic understanding of the pathogenesis of visceral leishmaniasis with respect to testosterone. We examined the relationship between serum testosterone and cholesterol levels, antigen induced Interleukin-10 (IL-10) and Interferon-gamma (IFN-γ) and production by Peripheral Blood Mono Nuclear Cells (PBMCs) and parasite burden as determined by microscopic examination on male patients (n = 18) with VL and gender-and age-matched controls (n = 10). Testosterone plasma levels were found to be up regulated in VL patients as compared to healthy controls. In severely infected patients, the mean testosterone concentration was observed to be increased compared with other VL patients (p<0.001). Further, serum cholesterol level was found much down regulated during severe infection of VL (p<0.005) as compared to healthy control. Further an in-vitro stimulation of PBMCs of VL patients with exogenous testosterone resulted in an increase IL-10 production with a subsequent decline in host protective IFN-γ response. This study suggests that testosterone level might be linked to immuno-pathogenicity of VL infection. Whether testosterone level is probably a marker of severe VL infection with an immunosuppressive effect needs to be validated further.

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Testosterone signaling in T cells and macrophages

Cited by 107 publications

References 15 publications

Testosterone Is Responsible for Enhanced Susceptibility of Males to Ischemic Renal Injury

Testosterone Is Responsible for Enhanced Susceptibility of Males to Ischemic Renal Injury

Non-genomic actions of androgens

Association of Testosterone and Cholesterol Level in Modulation of Immunity and Severity of Disease in Visceral Leishmaniasis Patients-a Preliminary Study

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