Activation of PPARgamma reduces antioxidant-induced hypercorticoidism by down-regulating MC2R expression into the adrenal glands

AMANDA S. CHAVES; MARIA FLORENCIA PACINI; MARCO A. MARTINS; RAÍSSA D. VENTURA; FLORENCIA B. GONZALEZ; PATRÍCIA M. R. SILVA; NATHALIA S. MAGALHÃES; ANA ROSA PEREZ; VINICIUS F. CARVALHO

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2020 vol. 156 p. 137 - 143

0891-5849

We previously demonstrated that oral supplementation with antioxidants induced hyperactivity of hypothalamus-pituitary-adrenal through an up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal. This study analyzed the role of peroxisome proliferator-activated receptor (PPAR)-γ on HPA axis hyperactivity induced by antioxidants. Male Swiss-Webster mice were orally treated with N-acetylcysteine (NAC) for 1, 3, 5, 10, 15, or 18 consecutive days. The PPAR-γ agonist rosiglitazone and/or antagonist GW9662 were injected i.p. daily for 5 consecutive days concomitantly with NAC treatment. Rosiglitazone treatment inhibited NAC-induced adrenal hypertrophy and hypercorticoidism. Rosiglitazone also significantly reversed the NAC-induced increase in the MC2R expression in adrenal, but nor steroidogenic acute regulatory protein (StAR). NAC treatment reduces the expression of PPARγ in the adrenals, however rosiglitazone did not restored the expression of this citoprotective gene. In addition, GW9662 blocked the ability of rosiglitazone to restore plasma corticosterone levels in NAC-treated mice. In conclusion, our findings showed that antioxidant-induced hypercorticoidism through down-regulation of PPARγ expression in the adrenals. Furthermore, the activation of PPARγ by rosiglitazone inhibited adrenal steroidogenesis induced by antioxidant through a down-regulation of ACTH receptor expression.