Pituitary-adrenal axis during human development.

Abstract

Investigation of early human fetal tissue has helped us elucidate the onset of the activation of the pituitary-adrenal axis during human development. Adrenal steroidogenesis and ACTH secretion from the pituitary starts at 7–8 weeks postconception, providing the rationale for prenatal treatment using dexamethasone offered to fetuses at risk of 21-hydroxylase deficiency (21-OHD). Fluctuation of 3beta-hydroxysteroid dehydrogenase (HSD3B2) in human fetal adrenal has several significant meanings. Its activity during early gestation is essential for inhibiting androgen production in the adrenal and safeguarding normal female sexual development. The enzyme may be reduced during mid-gestation in order to maintain pregnancy and to prevent preterm labor. Its reappearance in late gestation is also crucial for fetal maturation and parturition at term. Late-onset circulation failure observed in extremely low birth weight newborns may be associated with the paucity of HSD3B2 in their adrenals. In fetuses with 21-OHD, a proportion of increased 17alpha-hydroxyprogesterone may be converted to dihydrotestosterone through the backdoor pathway and contribute to the virilization of female fetuses.