The human fetal adrenal comprises the fetal zone which produces adrenal androgens (predominantly DHEA and DHEAS) and the definitive zone which will give rise to the adult adrenal cortex after birth. Together with the fetal liver and the placenta, it forms the fetal-placental unit which produces a variety of estrogens from androgen precursors. Although steroid production by the fetal adrenal seems not essential for fetal survival during pregnancy, steroid biosynthetic defects (such as 3β-hydroxysteroid dehydrogenase, 21-hydroxylase or 11-hydroxylase deficiency, and P450 oxidoreductase or aromatase deficiency) may lead to virilization of 46,XX fetuses through unbalanced androgen metabolism in the fetalplacental unit. Even under physiologic conditions the normal fetal adrenal shifts from androgen to cortisol production during the critical window of the development of the external genitalia from 6 to 12 weeks gestation to safeguard the female phenotype. The fetal testis starts producing testosterone around 7 weeks gestation. Normal testosterone and dihydrotestosterone (DHT) production in the first trimester are crucial for proper virilization of the external genital organs in 46,XY fetuses. Therefore, any defect affecting testosterone/DHT synthesis or action will lead to lack of virilization or undervirilization in males. Such defects may affect overall steroidogenesis (e.g. StAR) or sex steroid synthesis only (e.g. HSD17B3 or SRD5A2). Moreover, recently identified human mutations in genes of the alternative, backdoor pathway for DHT production establish a role of this novel pathway for male sex development. By contrast, the ovary seems steroidogenic quiescent during fetal life and estrogens may not play a major role in (female) sex development. In addition to being part of the fetal-placental unit, the placenta is a barrier for maternal steroids reaching the fetus. Such as placental 11β-HSD activity inactivates maternal cortisol to cortisone to protect the fetus. On the other hand, the placenta itself produces CRH and promotes cortisol production in both mother and fetus in the last trimester. Placental CRH seems in a positive feedback loop with fetal cortisol forming a cascade for rapid adrenal growth and steroidogenesis during late gestation and is possibly responsible for the involution of the fetal zone after birth.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology