Nonylphenol-induced hyperadrenalism can be reversed/alleviated by inhibiting of 11-β hydroxysteroid dehydrogenase type 1

• Developmental exposure to NP may induce hyperadrenalism and increase adipogenesis.
• Oral gavage with PF915275 inhibited the NP-induced increases in corticosterone levels and 11β-hydroxylase.
• The administration of PF915275 decreased the NP-induced expression of PPARγγ mRNA.
• The administration of PF915275 increased the expression of PPARαα protein and mRNA.
• PF915275 reversed/alleviated the impact of NP exposure during development.

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.