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

Abstract

ABSTRACT: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 (nNOS2/2) 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 nNOS2/2, 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 nNOS2/2 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.

Changes of testicular phosphorylated proteins in response to restraint stress in male rats

“…In the recent study, all parameters of adverse male reproductive system including decreased body weight in rats exposed to restraint stress (Fig. 1a and Table 1) were similar to those parameters previously documented (Orr and Mann, 1990;Carrasco and van de Kar, 2003;Zardooz et al, 2006;Weissman et al, 2009;Hari Priya and Sreenivasula Reddy, 2012;Lin et al, 2014;Prabsattroo et al, 2015). In explanation of weight loss (Table 1), it is known that testosterone activates the protein synthetic apparatus muscles and other organs while corticosterone increases protein catabolism and decreases protein synthesis.…”

“…(1) erectile dysfunction (Nathan, 1986;Ernst et al, 1993;Kennedy et al, 1999), (2) decrease of sperm quality (Almeida et al, 1998;Clarke et al, 1999;Hari Priya and Sreenivasula Reddy, 2012;Hari Priya et al, 2014;Rao et al, 2015;Zhang et al, 2015), (3) decrease of testosterone levels (Orr and Mann, 1990;Retana-Márquez 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;Aziz et al, 2013;Prabsattroo et al, 2015). Indeed, the corticosterone levels are markedly elevated under a restraint immobilization condition (Bhatia et al, 2011;Prabsattroo et al, 2015).…”

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

“…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, 2009) knockout mice failed to show a significant elevation of testicular NO production following 3 h acute IMO in both knockout and wild type mice. These observations may lead to conclusion that testicular NO is not affected by IMO exposure.…”

“…Recent studies on iNOS (Weissman et al. , 2007) and nNOS (Weissman et al. , 2009) knockout mice failed to show a significant elevation of testicular NO production following 3 h acute IMO in both knockout and wild type mice.…”

Time-Course Changes of Steroidogenic Gene Expression and Steroidogenesis of Rat Leydig Cells after Acute Immobilization Stress

“…NOS2 synthesizes NO, which is a reactive free radical, acting as a biologic mediator in several processes [ 38 ]. Several studies debate the possible involvement of NOS signaling in acute stress-mediated suppression of Leydig cells [ 28 , 38 , 39 ]. However, knockout of several NOS isoforms did not antagonize the stress-mediated action on testosterone production [ 38 , 39 ], suggesting that NO signals in the acute stress-mediated action are minimal.…”