Non-classical actions of testosterone: an update

Rahman, Faisal; Christian, Helen C.

doi:10.1016/j.tem.2007.09.004

Cited by 179 publications

(111 citation statements)

References 87 publications

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“…Most importantly, activation of mARs with testosterone or membrane-impermeable testosterone-BSA (T-BSA) conjugates results in induction of anti-tumor responses and inhibition of cell motility via actin cytoskeleton re-organization in various prostate and breast cancer cell lines (15,20,21,26). For recent reviews on androgen rapid actions, see (27,28).…”

Section: Introductionmentioning

confidence: 99%

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

et al. 2008

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In recent years, membrane androgen receptors (mARs) have been identified in prostate and breast tumor cells, and their activation by specific mAR ligands was linked to the regulation of crucial cell responses, such as cell growth, motility, and apoptosis. Analysis of the molecular signals triggered by mAR in the presence of anti‐androgens has clearly differentiated mAR‐dependent biological actions from those induced by the activation of the classical intracellular androgen receptors (iARs). In this review, we summarize the specific cellular events attributed to mAR activation and the experimental results on distinct non‐genomic signaling cascades operating in various tumor cells independently of the iAR. Furthermore, we discuss the crucial role of actin cytoskeleton organization and signaling in mediating mAR responses. Finally, we assess the clinical impact of the reported mAR‐induced apoptotic regression of prostate cancer cells both in vitro and in vivo and discuss the potential role of mAR as a novel therapeutic target. © 2008 IUBMB IUBMB Life, 61(1): 56–61, 2009

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Section: Introductionmentioning

confidence: 99%

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

et al. 2008

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“…1,2 Nonclassical pathways of androgen action also have been identified that do not involve nuclear androgen receptor-mediated transcriptional activation of target genes. 3 However, the central role of androgens acting through the androgen receptor in the regulation of male physiology is elegantly illustrated by androgen insensitivity syndrome where 46XY males possessing a mutated androgen receptor unresponsive to androgen have the outward appearance of normal females. 4 …”

Section: Introductionmentioning

confidence: 99%

Are declining testosterone levels a major risk factor for ill-health in aging men?

Yeap

2008

Int J Impot Res

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As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone compared with total testosterone concentrations. Lower testosterone levels have been associated with poorer cognitive function, and with impaired general and sexual health in aging men. Recently, lower testosterone levels have been linked with metabolic syndrome and type II diabetes, both conditions associated with cardiovascular disease, and shown to predict higher overall and cardiovascular-related mortality in middle-aged and older men. However, reverse causation has to be considered, as systemic illness may result in reduced testosterone levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. Furthermore, these conditions may overlap, for example aging, lower testosterone levels, erectile dysfunction and cardiovascular disease are interrelated. Cross-sectional and longitudinal observational studies may be informative. However, ultimately randomized controlled trials of testosterone therapy are needed to clarify its role in the maintenance of general and sexual health in aging men. Testosterone therapy should be considered in hypogonadal men who meet rigorous criteria for the diagnosis of androgen deficiency. Additional consideration should be given to designing and testing interventions that may prevent or ameliorate the age-related decline in testosterone levels in men.

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“…There is also evidence for nongenomic testosterone actions through both a membrane-associated form of the classical androgen receptor and a distinct receptor with pharmacologic characteristics of a heterotrimeric G protein coupled receptor (11).…”

Section: Physiology Of Testosterone Actions On the Vasculaturementioning

confidence: 99%

“…In addition, sex steroids modulate inflammation, coagulation, and other functions that indirectly affect the vasculature (13,14). Rapid CV actions of sex steroids, such as vasodilation, are mediated by nongenomic pathways (11,15,16). Longer term actions occur via testosterone's transcriptional pathway (17).…”

Section: Physiology Of Testosterone Actions On the Vasculaturementioning

confidence: 99%

Testosterone therapy and cardiovascular risk

Walsh

Kitchens

2015

Trends in Cardiovascular Medicine

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Endogenous testosterone levels are inversely associated with cardiovascular risk in older men and men with cardiovascular disease. Current data on cardiovascular outcomes of testosterone therapy include only observational studies and adverse event monitoring in short term trials that were not designed to measure cardiovascular outcomes. These studies have yielded conflicting results, and some have raised concerns that testosterone therapy may increase cardiovascular risk. A well designed, adequately powered, prospective trial will ultimately be required to clarify whether testosterone therapy impacts cardiovascular outcomes. This review describes the findings and limitations of recent studies of cardiovascular risk in older men on testosterone therapy and discusses some of the mechanisms through which testosterone may modify cardiovascular risk

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Non-classical actions of testosterone: an update

Cited by 179 publications

References 87 publications

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

Membrane androgen receptor activation in prostate and breast tumor cells: Molecular signaling and clinical impact

Are declining testosterone levels a major risk factor for ill-health in aging men?

Testosterone therapy and cardiovascular risk

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