Dexamethasone affects human fetal adrenal steroidogenesis and subsequent ACTH response in an ex vivo culture model

Introduction Administration of dexamethasone (DEX) has been used experimentally to suppress androgenization external genitalia in 46,XX fetuses with congenital adrenal hyperplasia. Despite this, the prenatal biological mechanism-of-action DEX on fetal development is not known. This study aimed examine direct effects human (HFA) steroidogenic activity including possible subsequent response ACTH-stimulation. Methods Human tissue from 30 (1 st trimester) were cultured ex vivo A) (10 µm) for 14 days, or B) 10 days followed by ACTH nM) 4 days. DEX-mediated HFA morphology, viability, and apoptosis (immunohistochemistry), gene expression (quantitative PCR), steroid hormone secretion (LC-MS/MS) investigated. Results DEX-treatment caused decreased androstenedione (p<0.05) increased cortisol (p<0.01) suggesting that gland may contribute negative feedback hypothalamic-pituitary-adrenal axis . An altered stimulation pre-treated included androgen reduced production (p<0.05), supporting clinical observations a temporary ACTH-response following DEX-treatment. Additionally, corticosterone was (p<0.0001) ACTH-stimulation initially DEX-treated HFAs. Discussion The observed suggest can cause steroidogenesis indicate requirement careful monitoring function prenatally neonates, particular focus their mineralocorticoid levels.