Role of Nuclear Receptors Steroidogenic Factor-1, DAX-1, and Estrogen Receptor

Steroid hormone biosynthesis by the fetal adrenal gland is crucial to the integrity and continuation of pregnancy, growth of the fetal and maternal tissues, as well as perinatal homeostatic adaptation for extrauterine survival. The adrenal cortex in the primate undergoes a remarkable morphological and functional remodeling such that the fetal adrenal cortex transforms into an adult adrenal cortex capable of independent glucocorticoid and mineralocorticoid biosynthesis. This architectural and functional transition from a fetal to an adult adrenal cortex ensures self-sufficient existence of the neonate. The fetal zone of the adrenal cortex, which is unique to the fetal adrenal, atrophies soon after birth (1–5). This predominant zone, which forms 80–90% of the fetal adrenal cortex synthesizes dehydroepiandrosterone sulfate (DHEA-S), the precursor hormone for estrogen biosynthesis by the placenta (6–9). During late gestation, placental estrogen promotes fetal adrenal cortisol biosynthesis, which supports the growth and maturation of various fetal tissues including the lung, thyroid, liver, and the gut (9,10). This placental estrogen is also instrumental in regulating fetal cortisol levels throughout pregnancy. In addition to feto-placental steroidogenesis, estrogen plays a critical role in the maintenance of pregnancy, regulation of maternal cardiovascular system, control of uteroplacental blood flow and neovascularization of the placenta, maintenance of uterine quiescence, and progesterone-mediated immunosuppression to allow implantation of the embryo in the uterus (9).