Endocrine Abstracts

Introduction: The adrenal gland dominates in human fetal steroid endocrinology and produces large amounts of Δ5 androgens. Adrenal development in the human is poorly understood, and species differences make animal models only partially relevant. In this study we measured the steroid content of the human adrenal during fetal development and determined whether maternal smoking affects adrenal steroid concentrations or associated steroidogenic enzymes.

Methods: 109 human fetal adrenals were obtained from elective terminations (REC 04/S0802/21) of second trimester fetuses between 11 and 21 weeks of gestation. Fetuses were grouped according to sex, gestational age and maternal smoking. Steroids extracted from these adrenals were quantified by LC–MS and enzyme expression analysed by RT-qPCR, Western blot and immunohistochemistry.

Results: The most abundant steroid (ng/mg of tissue) in the human fetal adrenal was pregnenolone, followed by dehydroepiandrosterone-sulphate and 17-hydroxyprogesterone (17OHP). Most steroids were unchanged during the second trimester although relative production of pregnenolone and corticosterone decreased between weeks 12 and 19 (P=0.002 and P=0.06, respectively). While steroid levels were similar between male and female fetuses, maternal smoking increased 16-hydroxyprogesterone (P=0.04) and deoxycorticosterone (P=0.003) levels in male fetuses only. Protein expression of steroidogenic enzymes CYP17A1 and CYP21A2 increased throughout the second trimester but were unaffected by sex or maternal smoking. Transient protein expression of HSD3B in the adrenal fetal zone was observed at 12–13 weeks. Maternal smoking was associated with increased mRNA of transcription factors, SF-1 (P=0.04: males) and GATA-6 (P<0.001: both sexes), which are involved in steroidogenesis and cell proliferation.

Conclusions: The rate of androgen and corticosteroid production is limited predominantly by expression of CYP17A1 and CYP21A1 as reflected by high levels of pregnenolone and 17OHP. Maternal smoking affects human fetal adrenal development in terms of changes in transcriptional regulation and steroid production, particularly in males, which may impact on post-natal health.