Turning the spotlight on the C11-oxy androgens in human fetal development

Abstract

Research into the biosynthesis of C11-oxy C₁₉ steroids during human fetal development, specifically fetal adrenal development and during the critical period of sex differentiation, is currently lacking. Cortisol, which possesses a C11-hydroxyl moiety has, however, been firmly established in this context. Compelling questions are whether the C11-oxy C₁₉ steroids (11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketoandrostenedione and 11-ketotestosterone [11KT]) and the C11-oxy C₂₁ steroids (11β-hydroxyprogesterone and 11-ketoprogesterone) are biosynthesised during gestation, and whether these hormones circulate between the placenta and the developing fetus, and between the placenta and the mother. This review will consider the role of cortisol, 11KT and 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) in determining the sex of teleost fish, while these hormones and 11βHSD2 will also be discussed with regards to murine mammals. The focus of the review will shift to highlight the potential role of C11-oxy steroids in human fetal development based on the timely expression of steroidogenic enzymes in the adrenal, testes and ovary, as well as in the placenta; summarising reported evidence of C11-oxy steroids in neonatal life.

Keywords: 17β-hydroxysteroid dehydrogenase type 2/4 (HSD17B2/4); Aldo-keto reductase family 1 member C3 (AKR1C3); Cytochrome P450 11β-hydroxylase (CYP11B1); Full-term newborns; Oxygenated C19 steroids; Sex differentiation; Teleost fish.