Thiazolidinediones Influence Plasma Steroids of Male Obese Zucker Rats

Abstract

Insulin sensitizing thiazolidinediones (TZDs) inhibit steroidogenic enzyme activities in vitro and affect plasma steroids in women with polycystic ovary syndrome. This study was to examine TZD action on circulating steroids in male genetically obese Zucker rats (fa/fa), which were treated with troglitazone or rosiglitazone (0.3% and 0.01% food admixture, respectively) and were compared to untreated obese and lean littermates. After 36 days of TZD administration, obesity- associated derangement of carbohydrate metabolism was ameliorated (e.g., insulin-stimulated glucose oxidation by isolated soleus muscle, nmol/g/h: lean controls, 1049 ± 100; obese controls, 518 ± 30; troglitazone-treated obese, 672 ± 43; rosiglitazone-treated obese, 761 ± 77; p < 0.01 each vs. obese controls). While plasma pregnenolone and testosterone were neither affected by obesity nor by TZDs, a marked reduction of 17-hydroxyprogesterone in obese vs. lean controls (27 ± 3 vs. 58 ± 10 ng/dl; p < 0.01) was partially reversed by TZD treatment (46 ± 5 and 48 ± 9 ng/dl for troglitazone and rosiglitazone, respectively; p< 0.02 each vs. untreated obese). Plasma 5-α-dihydrotestosterone, in contrast, was not reduced by obesity (76± 9 vs. 59 ± 7 ng/dl in obese vs. lean controls; n.s.) but blunted by TZD treatment of obese rats (38 ± 4 and 44 ± 3 ng/dl for troglitazone and rosiglitazone, respectively; p < 0.05 each vs. untreated obese). We conclude that (i) oral TZD treatment influences circulating steroid concentrations of male obese Zucker rats, and (ii) these effects are at least in part mediated via mechanisms other than those underlying TZD-induced insulin sensitization.