We previously observed that nonylphenol (NP) exposure during development resulted in increases in body weight and hyperadrenalism in adult male offspring. The mechanism of hyperadrenalism includes the primary activation of the adrenal gland and the conversion of inactive glucocorticoids to active glucocorticoids by 11 beta-HSD1. The inhibition of 11 beta-HSD1 is investigated as a new therapeutic approach. This study examined the effect of PF915275 (a selective 11 beta-HSD1 inhibitor) on hyperadrenalism and adipogenesis in male rats exposed to NP during development. The results showed that treatment with the 11 beta-HSD1 inhibitor PF915275 reversed/alleviated NP-induced hyperadrenalism via the following mechanisms: (1) decreasing serum corticosterone, 11 beta-hydroxylase, and aldosterone synthase levels; (2) significantly increasing PPAR alpha protein and mRNA expression. In adipose tissue, NP significantly increased PPAR gamma mRNA expression, whereas PF915275 significantly decreased the level of mRNA expression; and (3) the expression of key regulators/enzymes in the adipogenesis metabolic pathway was also modulated. (C) 2016 Elsevier B.V. All rights reserved.
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 卷: 44 頁碼: 1-12
