Prenatal nicotine exposure aggravated abnormal adrenal function and its gender differences in adult offspring rats with high-fat diet / 中国药理学通报

ABSTRACT

Aim To explore the alterations of blood corticosterone (CORT) level and adrenal steroidogenic function,as well as its sex specificity in intrauterine growth retardation (IUGR) rats induced by prenatal nicotine exposure (PNE) with high-fat diet (HFD) after birth,and to make clear its mechanism through insulin-like growth factor-1 (IGF-1) signaling pathway.Methods IUGR model was established by PNE (2.0mL · kg-1 · d-1),and the offspring rats were administered with HFD until postnatal week (PW) 24 after weaning.Blood CORT concentration,adrenal steroidogenesis enzymes,expressions of IGF-1 signaling pathway and 11β-HSDs/CR system were tested.Results Compared with HFD control group,the CORT concentration in male offspring of PNE group represented a decrease trend,while an increase trend in female;the expressions of adrenal steroidogenesis enzymes (such as StAR,3β-HSD and P450cll) in male offspring decreased,while increased in female offspring (such as SF-1 and P450c21);the expressions of IGF-1 signalling pathway (IGF-1 and IGF-1R) in male offspring increased,and they significantly increased in female offspring;the expression levels of 11 β-HSD2 and GR decreased,but 11β-HSD1/11β-HSD2 ratio was enhanced in male PNE group,while in female PNE group,the corresponding gene expressions increased.Conclusions PNE could induce abnormal alterations of adrenal steroidogenic function,and exhibit apparent gender differences.The potential mechanism is related to low adrenal steroidogenesis function programming induced by nicotine and catch-up growth mediated by IGF-1 after birth.