Pediatric research
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The genetic mechanisms underlying the regulation of adrenarche are unknown. The aim of the study was to find out whether ACTH receptor (MC2R) promoter polymorphism associates with premature adrenarche (PA) and its characteristics. DNA samples of 74 prepubertal children with PA and their age- and gender-matched 97 healthy controls were genotyped for the -2 bp T/C diallelic MC2R promoter polymorphism (MC2R -2 T>C) All children were examined clinically, and hormonal measurements after an overnight fast and a low-dose ACTH stimulation test were performed. ⋯ The frequency of the MC2R -2 T>C polymorphism was significantly higher in PA children with premature pubarche than in those with milder signs of PA or in control children (p = 0.04). In children with PA, the polymorphism associated with higher baseline serum dehydroepiandrosterone (p = 0.03), androstenedione (p = 0.02), plasma ACTH (p = 0.03) levels and with lower birth weight (p = 0.02). Our study provides evidence that the MC2R promoter polymorphism modulates the hypothalamo-pituitary-adrenal axis in children and may play a role in altered regulation of adrenarche.
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Literature suggests that glucocorticoid (GC) exposure during early life may have long-term consequences into adult life. GCs are known to influence hepatic bile acid synthesis and their transport within the enterohepatic circulation. This study addresses effects of early postnatal exposure to GC on hepatic expression of key genes in bile acid metabolism and bile acid kinetics in adult rats. ⋯ DEX acutely induced hepatic mRNA levels of cholesterol 7alpha-hydroxylase (Cyp7a1), cholesterol 27-hydroxylase (Cyp27), and in particular sterol 12alpha-hydroxylase (Cyp8b1), whereas expression of the bile acid transporters bile salt export pump (Bsep) and sodium taurocholate cotransporting polypeptide (Ntcp) was moderately affected. Neonatal DEX administration led to increased bilary lipid secretion, decreased Cyp8B1 mRNA expression and a 3-fold higher Cyp7a1/Cyp8b1 mRNA ratio in rats at week 8 compared with age-matched controls without alterations in bile acid kinetics. Therefore, neonatal DEX administration causes altered gene expressions later in life that are not translated into quantitative changes in bile acid kinetics.