Spinal cord injury induced arrest in estrous cycle of rats is ameliorated by S-nitrosoglutathione: novel therapeutic agent to treat amenorrhea.
BACKGROUND
Amenorrhea following spinal cord injury (SCI) has been well documented. There has been little research on the underlying molecular mechanisms and therapeutics.


OBJECTIVE
The purpose of the present study was to investigate the effect of GSNO in ameliorating SCI-induced amenorrhea through affecting the expression of CX43, NFkB, and ERβ protein.


METHODS
SCI was induced in female SD rats at the T9-T10 level. Estrous stage was determined by vaginal smear. GSNO (50 µg/kg body weight) was gavage fed daily. Animals were sacrificed on day 7 and 14 post SCI. Ovaries were fixed for histological and biochemical studies. Expression levels of ERβ, CX-43, and NFkB were analyzed by Western blot and immunofluorescence.


METHODS
GSNO hastens resumption of the estrous cycle following SCI-induced transient arrest.


RESULTS
Resumption of estrous cycle was hastened by GSNO. Atretic and degenerating follicles seen in the ovary of SCI rats on day 14 post-SCI were decreased in GSNO treated animals. The increased CX43 expression observed with SCI ovary was decreased by GSNO. ERβ expression decreased significantly on day 7 and 14 post-SCI and was restored with GSNO treatment. Following SCI, NFkB expression was increased in the ovarian follicles and the expression was reduced with GSNO administration. The number of terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate (UTP) nick end labeling positive follicular and luteal cells was increased after SCI. GSNO-treated animals had significantly fewer apoptotic cells in the ovary.


CONCLUSIONS
SCI-induced amenorrhea is accompanied by an increase in CX43 expression and a decrease in ERβ expression. SCI animals treated with GSNO resumed the estrous cycle significantly earlier. These results indicate a potential therapeutic value for GSNO in treating amenorrhea among SCI patients.
Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA.
Anandakumar
A
Shunmugavel
Mushfiquddin
M
Khan
Peter C-te
PC
Chou
Inderjit
I
Singh
D000568:Amenorrhea / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D015153:Blotting, Western; D018031:Connexin 43 / Q000032:analysis / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000032:analysis / Q000096:biosynthesis; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005455:Fluorescent Antibody Technique; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis; D010053:Ovary / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications*
D018031:Connexin 43; D047629:Estrogen Receptor beta; D016328:NF-kappa B; D026422:S-Nitrosoglutathione