Testosterone production in mice lacking inducible nitric oxide synthase expression is sensitive to restraint stress.
Immobilization stress (IMO) induces a rapid increase in glucocorticoid secretion [in rodents, corticosterone CORT)] and this is associated with decreased circulating testosterone (T) levels. Nitric oxide (NO), a reactive free radical and neurotransmitter, has been reported to be produced at higher rates in tissues such as brain during stress. The biosynthesis of T is also known to be dramatically suppressed by NO. Specifically, the inducible isoform of nitric oxide synthase (iNOS) was directly implicated in this suppression. To assess the respective roles of CORT and NO in stress-mediated inhibition of T production, adult wild-type (WT) and inducible nitric oxide synthase knockout (iNOS(-/-)) male mice were evaluated. Animals of each genotype were assigned to either basal control or 3-h IMO groups. Basal plasma and testicular T levels were equivalent in both genotypes, whereas testicular weights of mutant mice were significantly higher compared with WT animals. Exposure to 3-h IMO increased plasma CORT and decreased T concentrations in mice of both genotypes. Testicular T levels were also affected by stress in WT and mutant males, being sharply reduced in both genotypes. However, the concentrations of nitrite and nitrate, the stable metabolites of NO measured in testicular extracts, did not differ between control and stressed WT and iNOS(-/-) mice. These results support the hypothesis that CORT, but not NO, is a plausible candidate to mediate rapid stress-induced suppression of Leydig cell steroidogenesis.
Weissman
Ben A
BA
Department of Pharmacology, Israel Institute for Biological Research, Ness Ziona, Israel. baw@iibr.gov.il
Sottas
Chantal M
CM
Zhou
Ping
P
Iadecola
Costantino
C
Hardy
Matthew P
MP
D000818:Animals; D003345:Corticosterone / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000378:metabolism*; D013737:Testis / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism; D013739:Testosterone / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood
D009569:Nitric Oxide; D013739:Testosterone; D052247:Nitric Oxide Synthase Type II; D003345:Corticosterone