Beneficial effects of pioglitazone and metformin in murine model of polycystic ovaries via improvement of chemerin gene up-regulation.
BACKGROUND
Polycystic ovary syndrome (PCO) is recognized as the most common endocrinopathy in female. Chemerin is a novel adipocytokine that is expressed in ovary and upregulated in adipose tissue of obese, PCO patients. To date there is no report about the regulation of ovarian chemerin gene expression after PCO induction and treatment by insulin sensitizing drugs including pioglitazone and metformin. Thirty female rats were divided into six experimental groups with five rats in each group including control group, PCO group (i.m injection of 4 mg estradiol benzoate for 40 days), metformin treated (200 mg/kg/day for 21 days), pioglitazone treated (20 mg/kg/day, for 21 days), PCO + metformin and PCO + pioglitazone. PCO was detected by microscopic observation of vaginal smear and treatment by metformin and pioglitazone was initiated one week after that. Ovarian chemerin expression was analyzed by real time PCR and western blotting.


RESULTS
Our results demonstrated that PCO induction resulted in elevation of chemerin mRNA and protein levels in ovary in concomitant with incidence of insulin resistance and increasing androgen and progesterone production. We observed that metformin and pioglitazone attenuated ovarian chemerin expression and improved insulin resistance and abnormal steroid production in PCO rats.


CONCLUSIONS
Based on data presented here we concluded that alteration of ovarian chemerin expression may has important role in PCO development and manipulation of chemerin expression or signaling by pioglitazone or metformin can be a novel therapeutic mechanism in the treatment of PCO patients by these drugs.
Nahid
N
Kabiri
Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran. m.tabandeh@scu.ac.ir.
Mohammad Reza
MR
Tabandeh
Seyed Reza Fatemi
SR
Tabatabaie
D054392:Adipokines / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D018925:Chemokines; D004195:Disease Models, Animal; D004338:Drug Combinations; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins; D008687:Metformin / Q000008:administration & dosage* / Q000627:therapeutic use; D000077205:Pioglitazone; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000627:therapeutic use
D054392:Adipokines; D018925:Chemokines; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; C560738:Rarres2 protein, rat; D045162:Thiazolidinediones; D008687:Metformin; D000077205:Pioglitazone