Testosterone production in mice lacking inducible nitric oxide synthase expression is sensitive to restraint stress

Weissman, Ben Avi; Sottas, Chantal M.; Zhou, Ping; Iadecola, Costantino; Hardy, Matthew P.

doi:10.1152/ajpendo.00412.2006

Cited by 19 publications

(25 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…; Weissman et al . ). There are, however, different results suggest that testosterone also plays a role in the regulation of stress‐induced HPA activity, including the release of corticosterone, via modulation of adrenocorticotropic hormone and 5α‐reductase within the central nervous system (Rubinow et al .…”

Section: Discussionmentioning

confidence: 97%

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model

Son

Lee

Kim

et al. 2015

Journal of Neurochemistry

View full text Add to dashboard Cite

Among sex hormones, estrogen is particularly well known to act as neuroprotective agent. Unlike estrogen, testosterone has not been well investigated in regard to its effects on the brain, especially under psychological stress. To investigate the role of testosterone in oxidative brain injuries under psychological stress, we adapted an orchiectomy and restraint stress model. BALB/c mice were subjected to either an orchiectomy or sham operation. After allowing 15 days for recovery, mice were re-divided into four groups according to exposure of restraint stress: sham, sham plus stress, orchiectomy, and orchiectomy plus stress. Serum testosterone was undetectable in orchiectomized groups and restraint-induced stress significantly reduced testosterone levels in sham plus stress group. The serum levels of corticosterone and adrenaline were notably elevated by restraint stress, and these elevated hormones were markedly augmented by orchiectomy. Two oxidative stressors and biomarkers for lipid and protein peroxidation were significantly increased in the cerebral cortex and hippocampus by restraint stress, while the reverse pattern was observed in antioxidant enzymes. These results were supported by histopathological findings, with 4-hydroxynonenal staining for oxidative injury and Fluoro-Jade B staining showing the degenerating neurons. The aforementioned patterns of oxidative injury were accelerated by orchiectomy. These findings strongly suggest the conclusion that testosterone exerts a protective effect against oxidative brain damage, especially under stressed conditions.

show abstract

Section: Discussionmentioning

confidence: 97%

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model

Son

Lee

Kim

et al. 2015

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…NO is a small, diffusible, short-lived free radical gas active in diverse biological responses. In the testis, NO modulates germ cell viability and development and coordinates the testicular production of hormones and cytokines [23]–[26]. It has also been reported that testicular NO production is involved in compromised spermatogenesis in infertile men with varicocele [27].…”

Section: Discussionmentioning

confidence: 99%

Disturbed Relaxin Signaling Pathway and Testicular Dysfunction in Mouse Offspring upon Maternal Exposure to Simazine

Park

Bae

2012

PLoS ONE

View full text Add to dashboard Cite

Simazine is a triazine herbicide that is being widely applied worldwide and commonly detected in surface and groundwater. Despite its popular use in controlling weeds and algae, very limited information is available regarding its toxicity. In the present study, pregnant mice were orally exposed to low doses (0, 5, 50, or 500 µg/kg body weight per day) of simazine during gestation and lactation, during which no overt maternal toxic response was detected, and their offspring was assessed. Simazine-exposed male offspring showed decreased body, testicular, and epididymis weight, increased testicular apoptosis, and decreased sperm concentrations. Differentially-expressed genes in the testes of male offspring exposed to simazine were identified by DNA microarray, revealing 775 upregulated and 791 downregulated genes; among these, the relaxin-family peptide receptor 1 (Rxfp1), which is the receptor for relaxin hormone, was significantly downregulated. In addition, the expression of target genes in the relaxin pathway, including nitric oxide synthase 2 (Nos2) and Nos3, was significantly decreased in simazine-exposed F1 testes. Moreover, simazine inhibited NO release, and knockdown of Rxfp1 blocked the inhibitory action of simazine on NO production in testicular Leydig cells. Therefore, the present study provides a better understanding of the toxicities associated with the widely used herbicide simazine at environmentally relevant doses by demonstrating that maternal exposure interferes with the pleotropic relaxin-NO signaling pathway, impairing normal development and reproductive activity of male offspring.

show abstract

“…In contrast, inhibitory paracrine factors were released from interstitial cells and their inhibitory effect on NO production was evident in absence of seminiferous tubule and/or Sertoli cells. Recent studies on iNOS (Weissman et al. , 2007) and nNOS (Weissman et al.…”

Section: Discussionmentioning

confidence: 99%

“…, 1999). However, Weissman et al. (2007) reported that testicular NO originating from inducible NO synthase (iNOS) activation does not play an important role in the disruption of testosterone synthesis following IMO.…”

Section: Introductionmentioning

confidence: 99%

Structural complexity of the testis and PKG I / StAR interaction regulate the Leydig cell adaptive response to repeated immobilization stress

et al. 2010

View full text Add to dashboard Cite

The role of the structural complexity of the testis and the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway was analysed in adult male rats exposed to acute and repeated immobilization stress (IMO). In whole testis preparations, exposure to acute and repeated IMO caused an increase in NO production. In contrast, NO production was inhibited in interstitial cell preparations after exposure to all types of stress. In purified Leydig cell preparations, NO production was inhibited only after exposure to prolonged IMO. These findings indicate that biologically active compounds released from various testicular compartments exert both stimulatory and inhibitory effects on NO production. TaqMan Low Density Array of rat phosphodiesterases revealed a decrease in the expression of cGMP-specific phosphodiesterase 5 (PDE5) in Leydig cells of animals exposed to repeated IMO. In contrast, the expression of cGMP-dependent protein kinase type I (PKG I), total and phosphorylated steroidogenic acute regulatory protein (StAR), and PKG I/StAR immunoprecipitated complex was increased during repeated exposure to IMO. The increase in both total and phosphorylated StAR formation was effectively blocked by inhibition of PKG I in vitro. Thus, increased expressions of PKG I and StAR complex, accompanied by decreased PDE5 activity, suggest that the NO-cGMP signalling pathway and consequent activation of the StAR protein regulate the adaptive response of Leydig cells to repeated IMO stress.

show abstract

Testosterone production in mice lacking inducible nitric oxide synthase expression is sensitive to restraint stress

Cited by 19 publications

References 60 publications

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model

Testosterone depletion increases the susceptibility of brain tissue to oxidative damage in a restraint stress mouse model

Disturbed Relaxin Signaling Pathway and Testicular Dysfunction in Mouse Offspring upon Maternal Exposure to Simazine

Structural complexity of the testis and PKG I / StAR interaction regulate the Leydig cell adaptive response to repeated immobilization stress

Contact Info

Product

Resources

About