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From the * Department of Pharmacology, Israel
Institute for Biological Research, Ness Ziona, Israel; the
Center for Biomedical Research, Population
Council and the Rockefeller University, New York, New York; the
Division of Neurobiology, Department of
Neurology and Neuroscience, Weill Medical College of Cornell University, New
York, New York; and the Institute of
Neuroendocrinology and the 2nd Affiliated Hospital of Wenzhou Medical College,
Wenzhou, People's Republic of China.
| Correspondence to: Dr Ben Avi Weissman, Department of Pharmacology, IIBR, PO Box 19, Ness Ziona 74100, Israel (e-mail: aviw{at}iibr.gov.il); or Dr Ren-Shan Ge, Population Council, 1230 York Ave, New York, NY 10065 (e-mail: rge{at}popcbr.rockefeller.edu). |
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.
Key words: nNOS-null mice, testosterone, glucocorticoid, androgen
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