Background: Steroid hormones produced by the human fetal adrenals (HFA) are suggested to regulate intrauterine homeostasis and the maturation of certain fetal organs necessary for extrauterine life. Appropriate development and hormonal function of the HFA therefore are critical for normal fetal maturation and survival. Little is known about the possible relationship between the expression of steroidogenic enzymes and corresponding transcription factors in the HFA in vivo at the end of first trimester due to limited access to material at that fetal age.
Objective and hypotheses: The aim of the study was to investigate steroidogenesis in human fetal adrenocortical cells (HFACs) in vitro and to explore the ontogenetic expression profiles of steroidogenic enzymes and transcription factors in the HFA during the first trimester in vivo.
Method: Steroids produced by intact and ACTH-stimulated HFACs were analyzed by gas and liquid chromatography/mass spectrometry (GC-MS/MS and LC-MS/MS). Expression steroidogenic enzymes and transcription factors were explored by qPCR and automated Western blotting in the HFA at gestational week (GW) 912.
Results: ACTH-stimulated HFACs produced steroids of the Δ5pathway and had no potential to synthesize potent androgens at GW9-12. The HFA expressed high protein levels of CYP17A1 and CYP11B1 at GW11-12 and GW10-11, respectively, which were correlated with elevated expression of SF-1 and GATA-6. However, HSD3B2 peaked at GW10 but significantly decreased at GW11.
Conclusion: Our findings indicate that the HFACs are responsive to ACTH stimulation but have no potential to produce potent androgens at GW9-12. The onset of HFA steroidogenesis is a complex coordinated process that is tightly regulated by cooperative action of relevant transcription factors.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology