Changes in Adrenal Androgens and Steroidogenic Enzyme Activities From Ages 2, 4, to 6 Years: A Prospective Cohort Study

Abstract

Abstract Context The levels of adrenal androgens are increased through the action of steroidogenic enzymes with morphological changes in the adrenal zona reticularis. Objective We investigated longitudinal changes in androgen levels and steroidogenic enzyme activities during early childhood. Design and Participants From a prospective children’s cohort, the Environment and Development of Children cohort, 114 boys and 86 girls with available blood samples from ages 2, 4, and 6 years were included. Outcome Measurements Serum concentrations of adrenal androgens using liquid chromatography-tandem mass spectrometry and steroidogenic enzyme activity calculated by the precursor/product ratio. Results During ages 2 to 4 years, 17,20-lyase and dehydroepiandrosterone (DHEA) sulfotransferase activities increased (P < 0.01 for both in boys). During ages 4 to 6 years, 17,20-lyase activity persistently increased, but 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD activities decreased (P < 0.01 for all). Serum DHEA sulfate (DHEA-S) levels persistently increased from 2, 4, to 6 years, and DHEA, 17-hydroxyprogesterone, and androstenedione levels increased during ages 4 to 6 years (P < 0.01 for all). Serum DHEA-S levels during early childhood were associated with body mass index z-scores (P = 0.001 in only boys). Conclusion This study supports in vivo human evidence of increased 17,20-lyase and DHEA sulfotransferase activities and decreased 3β-HSD activity during early childhood.