Activation of PPARγ by Rosiglitazone Does Not Negatively Impact Male Sex Steroid Hormones in Diabetic Rats

Peroxisome proliferator-activated receptor gamma (PPAR γ ) activation decreased serum testosterone (T) in women with hyperthecosis and/or polycystic ovary syndrome and reduced the conversion of androgens to estradiol (E2) in female rats. This implies modulation of female sex steroid hormones by PPAR γ . It is not clear if PPAR γ modulates sex steroid hormones in diabetic males. Because PPAR γ activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPAR γ activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPAR γ activation on serum and intratesticular T, luteinizing hormone (LH), follicle stimulating hormone (FSH) and E2 concentrations in male Zucker diabetic fatty (ZDF) rats treated with the PPAR γ agonist rosiglitazone (a thiazolidinedione). Treatment for eight weeks increased PPAR γ mRNA and protein in the testis and elevated serum adiponectin, an adipokine marker for PPAR γ activation. PPAR γ activation did not alter serum or intratesticular T concentrations. In contrast, serum T level but not intratesticular T was reduced by diabetes. Neither diabetes nor PPAR γ activation altered serum E2 or gonadotropins FSH and LH concentrations. The results suggest that activation of PPAR γ by rosiglitazone has no negative impact on sex hormones in male ZDF rats.