Normal Responses to Restraint Stress in Mice Lacking the Gene for Neuronal Nitric Oxide Synthase

Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel.
Journal of Andrology (Impact Factor: 2.47). 04/2009; 30(5):614-20. DOI: 10.2164/jandrol.108.007443
Source: PubMed


The hormonal changes associated with immobilization stress (IMO) include a swift increase in corticosterone (CORT) concentration and a decrease in circulating testosterone (T) levels. There is evidence that the production of the short-lived neuromodulator nitric oxide (NO) is increased during stress in various tissues, including the brain. NO also suppresses the biosynthesis of T. Both the inducible and the neuronal isoforms of NO synthase (iNOS and nNOS, respectively) have been implicated in this suppression, but the evidence has not been conclusive. We used adult wild-type (WT) and nNOS knockout male mice (nNOS-/-) to assess the respective roles of CORT and nNOS-derived NO in stress mediated inhibition of T production. Animals were assigned to either basal control or 3-hour IMO groups. No difference in basal plasma and testicular T levels were observed between WT and nNOS-/-, although testicular weights of mutant mice were slightly lower compared to WT animals. The plasma contents of luteinizing hormone (LH) and CORT in unstressed mice of both genotypes were similar. Exposure to 3 hours of IMO increased plasma CORT and decreased T concentrations in mice of both genotypes. However, comparable levels of plasma LH and testicular nitrite and nitrate (NOx), NO stable metabolites, were detected in control and stressed WT and nNOS-/- mice. Adrenal concentrations of NOx declined after IMO, but the reduction was not statistically significant. These findings implicate CORT rather than NO generated by nNOS in the rapid stress-induced suppression of circulating T.

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Available from: Costantino Iadecola, Mar 28, 2015
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    • "It affects various physiological processes including reproductive functions. Numerous studies in human and experimental animals have shown that stress cause adverse effects in the male reproductive system: 1) erectile dysfunction (Nathan, 1986; Kennedy et al., 1999; Ernst et al., 1993), 2) decrease of sperm quality (Almeida et al., 1998; Clarke et al., 1999; Priya and Reddy, 2012; Priya et al., 2014; Rao et al., 2015; Zhang et al., 2015), 3) decrease of testosterone levels (Orr and Mann, 1990; Retana-Marquez et al., 2003; Weissman et al., 2009; Lin et al., 2014; Prabsattroo et al., 2015), and 4) damage to testicular tissue (Rai et al., 2003; 2004; Aziz et al., Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) ISSN 1673-1581 (Print); ISSN 1862-1783 (Online); "
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    ABSTRACT: Objective To investigate male reproductive parameters via changes of potential testicular protein markers in restraint-stress rats. Methods Male Sprague-Dawley rats were divided into two groups (non-immobilized control and restraint-immobilized/stress groups, n=8 each group). The stress animals were immobilized (12 h/d) by a restraint cage for 7 consecutive days. All reproductive parameters, morphology and histology were observed and compared between groups. In addition, the expression of steroidogenic acute regulatory (StAR) and phosphotyrosine proteins (previously localized in Sertoli and late spermatid cells) in testicular lysate was assayed by immuno-Western blotting. Results Testosterone level, sperm concentration and sperm head normality of stress rats were significantly decreased while the corticosterone level was increased as compared with the control (P<0.05). Histologically, stress rats showed low sperm mass in epididymal lumen and some atrophy of seminiferous tubules. Although the expression of testicular StAR protein was not significantly different between groups, changed patterns of the 131, 95, and 75 kDa testicular phosphorylated proteins were observed in the stress group compared with the control group. The intensity of a testicular 95-kDa phosphorylated protein was significantly decreased in stress rats. Conclusions This study has demonstrated the alteration of testicular phosphorylated protein patterns, associated with adverse male reproductive parameters in stress rats. It could be an explanation of some infertility in stress males.
    Full-text · Article · Dec 2015 · Journal of Zhejiang University SCIENCE B
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    ABSTRACT: 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.
    No preview · Article · Oct 2010 · International Journal of Andrology
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    ABSTRACT: Introduction: Chronic stress has been linked to many diseases. It has been proven to increase the susceptibility of different rat organs, such as the small intestine, colon, and brain, to inflammatory diseases. It has also been documented to cause hypogonadism in humans and laboratory animals. However, its effect on the pancreas, especially on the exocrine part, has received relatively little attention. Aim of the work: The aim of this study was to assess the effect of chronic stress induced by immobilization on the structure of both the endocrine and exocrine parts of the pancreas. In addition, the present study aimed to evaluate the effect of testosterone administration before stress exposure. Materials and methods: Thirty-two adult male albino rats were used in this study and were divided equally into four groups. Group I served as the control group. Group II received Testosterone Enanthate 6 days/week for 3 weeks intraperitoneally. Group III was exposed to chronic stress by immobilization sessions 4 h/day, 6 days/week, for 3 weeks. Group IV received Testosterone Enanthate 30 min before every exposure to immobilization stress sessions. All animals were sacrificed after 3 weeks. Biochemical, histological, histomorphometric, and statistical studies were conducted. Results: Testosterone administration alone did not have any significant effect on the structure of the pancreas. Chronic immobilization stress lowered testosterone and elevated blood glucose levels. It also had degenerating and inflammatory effects on pancreatic tissue. Administration of testosterone before stress sessions protected the pancreas from the effects of stress in male rats. Conclusion: Testosterone administration effectively protected the pancreas and compensated the decrease in serum testosterone levels after chronic immobilization stress.
    No preview · Article · Sep 2012 · Egyptian Journal of Histology
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