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

Peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 gamma. It is not clear if PPAR gamma modulates sex steroid hormones in diabetic males. Because PPAR gamma activation by thiazolidinedione increased insulin sensitivity in type 2 diabetes, understanding the long term impact of PPAR gamma activation on steroid sex hormones in males is critical. Our objective was to determine the effect of PPAR gamma 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 gamma agonist rosiglitazone (a thiazolidinedione). Treatment for eight weeks increased PPAR gamma mRNA and protein in the testis and elevated serum adiponectin, an adipokine marker for PPAR gamma activation. PPAR gamma 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 gamma activation altered serum E2 or gonadotropins FSH and LH concentrations. The results suggest that activation of PPAR gamma by rosiglitazone has no negative impact on sex hormones in male ZDF rats.