Androgen cell signaling pathways involved in neuroprotective actions

Pike, Christian J.; Nguyen, Thuy‐Vi V.; Ramsden, Martin; Yao, Meicun; Murphy, Michael P.; Rosario, Emily R.

doi:10.1016/j.yhbeh.2007.11.006

Cited by 116 publications

(84 citation statements)

References 140 publications

(194 reference statements)

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“…Decreased levels of glucocorticoids and androgens have been associated with an increased risk for neurodegenerative diseases (35,42). Androgens and glucocorticoids downregulate reactive gliosis after a neural injury (3,13).…”

Section: Discussionmentioning

confidence: 99%

Loss of the Androgen Receptor Cofactor p44/WDR77 Induces Astrogliosis

Vincent

Gao

et al. 2012

Molecular and Cellular Biology

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Astrogliosis is induced by neuronal damage and is also a pathological feature of the major aging-related neurodegenerative disorders. The mechanisms that control the cascade of astrogliosis have not been well established. In a previous study, we identified a novel androgen receptor (AR)-interacting protein, p44/WDR77, that plays a critical role in the proliferation and differentiation of prostate epithelial cells. In the present study, we found that deletion of the p44/WDR77 gene caused premature death with dramatic astrogliosis in mouse brain. We further found that p44/WDR77 is expressed in astrocytes and that loss of p44/WDR77 expression in astrocytes leads to growth arrest and astrogliosis. The astrocyte activation induced by deletion of the p44/WDR77 gene was associated with upregulation of p21Cip1 expression and NF-B activation. Silencing p21 Cip1 or NF-B p65 expression with short hairpin RNA (shRNA) abolished astrocyte activation and rescued the astrocyte growth inhibition induced by deletion of the p44/WDR77 gene. Our results reveal a novel role for p44/WDR77 in the control of astrocyte activation through p21Cip1 and NF-B signaling.

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Section: Discussionmentioning

confidence: 99%

Loss of the Androgen Receptor Cofactor p44/WDR77 Induces Astrogliosis

Vincent

Gao

et al. 2012

Molecular and Cellular Biology

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“…We speculate that testosterone and estrogen are likely acting via different pathways to induce protection. In support of this idea, recent observations suggest that nonaromatizable androgens mimic the protective properties of testosterone (Pike et al, 2008), and that activation of the androgen receptor stimulates mitogenactivated protein kinase signaling (MAPK) and subsequent inactivation of the proapoptotic protein Bad (Nguyen et al, 2005).…”

Section: Estrogen Endogenous Androgens and Apoptosismentioning

confidence: 97%

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

Kachadroka

Hall

Niedzielko

et al. 2010

Journal of Neurotrauma

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Several groups have recently shown that 17b-estradiol is protective in spinal cord injury (SCI). Testosterone can be aromatized to 17b-estradiol and may increase estrogen-mediated protection. Alternatively, testosterone has been shown to increase excitotoxicity in models of central nervous system (CNS) injury. These experiments test the hypothesis that endogenous testosterone in male rats alters 17b-estradiol-mediated protection by evaluating a delayed administration over a clinically relevant dose range and manipulating testicular-derived testosterone. Adult male Sprague Dawley rats were either gonadectomized or left gonad-intact prior to SCI. SCI was produced by a midthoracic crush injury. At 30 min post SCI, animals received a subcutaneous pellet of 0.0, 0.05, 0.5, or 5.0 mg of 17b-estradiol, released over 21 days. Hindlimb locomotion was analyzed weekly in the open field. Spinal cords were collected and analyzed for cell death, expression of Bcl-family proteins, and white-matter sparing. Post-SCI administration of the 0.5-or 5.0-mg pellet improved hindlimb locomotion, reduced urinary bladder size, increased neuronal survival, reduced apoptosis, improved the Bax=Bcl-xL protein ratio, and increased white-matter sparing. In the absence of endogenous testicular-derived androgens, SCI induced greater apoptosis, yet 17b-estradiol administration reduced apoptosis to the same extent in gonadectomized and gonadintact male rats. These data suggest that delayed post-SCI administration of a clinically relevant dose of 17b-estradiol is protective in male rats, and endogenous androgens do not alter estrogen-mediated protection. These data suggest that 17b-estradiol is an effective therapeutic intervention for reducing secondary damage after SCI in males, which could be readily translated to clinical trials.

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“…The protective action of androgens on tissues is currently receiving increased attention. The existence of beneficial effects of androgens on cardiovascular system, pancreas, neurons, testis, and bone has been reported (Erkkilä et al 1997, Morimoto et al 2005, Pike et al 2008, Chen et al 2010, Sánchez-Más et al 2010. It is well known that skeletal muscle is also a target tissue for androgens.…”

Section: Introductionmentioning

confidence: 99%

Testosterone exerts antiapoptotic effects against H2O2 in C2C12 skeletal muscle cells through the apoptotic intrinsic pathway

Pronsato¹,

Boland²,

Milanesi³

2012

Journal of Endocrinology

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Experimental data indicate that apoptosis is activated in the aged skeletal muscle, contributing to sarcopenia. We have previously demonstrated that testosterone protects against hydrogen peroxide (H 2 O 2 )-induced apoptosis in C2C12 muscle cells. Here we identified molecular events involved in the antiapoptotic effect of testosterone. At short times of exposure to H 2 O 2 cells exhibit a defense response but at longer treatment times cells undergo apoptosis. Incubation with testosterone prior to H 2 O 2 induces BAD inactivation, inhibition of poly(ADP-ribose) polymerase cleavage, and a decrease in BAX levels, and impedes the loss of mitochondrial membrane potential, suggesting that the hormone participates in the regulation of the apoptotic intrinsic pathway. Simultaneous treatment with testosterone, H 2 O 2 , and the androgen receptor (AR) antagonist, flutamide, reduces the effects of the hormone, pointing to a possible participation of the AR in the antiapoptotic effect. The data presented allow us to begin to elucidate the mechanism by which the hormone prevents apoptosis in skeletal muscle.

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Androgen cell signaling pathways involved in neuroprotective actions

Cited by 116 publications

References 140 publications

Loss of the Androgen Receptor Cofactor p44/WDR77 Induces Astrogliosis

Loss of the Androgen Receptor Cofactor p44/WDR77 Induces Astrogliosis

Effect of Endogenous Androgens on 17β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats

Testosterone exerts antiapoptotic effects against H2O2 in C2C12 skeletal muscle cells through the apoptotic intrinsic pathway

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