Normal responses to restraint stress in mice lacking the gene for neuronal nitric oxide synthase.
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.
Weissman
Ben A
BA
Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel. aviw@iibr.gov.il
Sottas
Chantal M
CM
Holmes
Michael
M
Zhou
Ping
P
Iadecola
Costantino
C
Hardy
Dianne O
DO
Ge
Ren-Shan
RS
Hardy
Matthew P
MP
D000818:Animals; D003345:Corticosterone / Q000097:blood; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D009573:Nitrites / Q000378:metabolism; D012149:Restraint, Physical / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology*; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis / Q000097:blood
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D013739:Testosterone; D007986:Luteinizing Hormone; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D003345:Corticosterone