title: Nonylphenol-induced hyperadrenalism can be reversed/alleviated by inhibiting of 11-β hydroxysteroid dehydrogenase type 1.
abstract: 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 11β-HSD1. The inhibition of 11β-HSD1 is investigated as a new therapeutic approach. This study examined the effect of PF915275 (a selective 11β-HSD1 inhibitor) on hyperadrenalism and adipogenesis in male rats exposed to NP during development. The results showed that treatment with the 11β-HSD1 inhibitor PF915275 reversed/alleviated NP-induced hyperadrenalism via the following mechanisms: (1) decreasing serum corticosterone, 11β-hydroxylase, and aldosterone synthase levels; (2) significantly increasing PPARα protein and mRNA expression. In adipose tissue, NP significantly increased PPARγ 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.
authors.affiliation: Department of Chemical and Materials Engineering, Chinese Culture University, Taipei 11114, Taiwan, ROC. Electronic address: llchiang@faculty.pccu.edu.tw.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Chang
authors.affiliation: Houston Fertility Specialists, Houston, TX 77054, USA.
authors.forename: Wan-Song A
authors.initials: WS
authors.lastname: Wun
authors.affiliation: Department of Physiology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan, ROC; Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei 11217, Taiwan, ROC; Medical Center of Aging Research, China Medical University Hospital, Taichung 40402, Taiwan, ROC; Department of Biotechnology, Asia University, Taichung 41354, Taiwan, ROC. Electronic address: pswang3879@gmail.com.
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000311:Adrenal Glands; D000308:Adrenocortical Hyperfunction / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000631:Aminopyridines / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: C525872:4'-cyanobiphenyl-4-sulfonic acid (6-aminopyridin-2-yl)amide; D052242:Adiponectin; D000631:Aminopyridines; D047493:PPAR alpha; D010636:Phenols; D012333:RNA, Messenger; D013449:Sulfonamides; D000450:Aldosterone; C025256:nonylphenol; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003345:Corticosterone
keywords: 11β-HSD1; Adipogenesis; Hyperadrenalism; Metabolic syndrome; NP; PF915275