SUN-039 Characterization of Human Adrenal Steroidogenesis during Fetal Development

Abstract

Context: The endocrine function of human fetal adrenals (HFA) is activated already during first trimester, but changes in adrenal steroidogenesis during fetal life are not well characterized. Objective: This study aimed to investigate HFA steroidogenesis by analyzing adrenal glands from 1st and 2nd trimester. Design and Setting: Male and female HFA samples from gestational week (GW) 8-19 were examined, including a total of 101 samples from 83 fetuses. Main Outcome Measure(s): Expression level of steroidogenic genes and protein expression/localization were determined by quantitative PCR and immunohistochemistry, respectively, and intra-adrenal steroid levels were quantified by LC-MS/MS. Results: Transcriptional levels of StAR, CYP11A1, CYP17A1, CYP21A2, CYP11B1/2 and SULT2A1 was significantly higher in 2nd trimester compared with 1st trimester (P<0.05), while expression levels of 3β-HSD2 and ARK1C3 were unaltered between GW 8-19. All investigated steroidogenic proteins were expressed in a distinct pattern throughout GW 8-19 with most enzymes expressed primarily in the fetal zone, except 3β-HSD1/2 which was mainly expressed in the definitive zone. The abundant steroidogenic enzyme expression was reflected in overall high intra-adrenal tissue concentrations of mineralocorticoids, glucocorticoids, and androgens; cortisol was the most abundant (1,071-2,723 ng/g tissue, in average) and testosterone levels the lowest (2-14 ng/g tissue, in average). Conclusions: The expression profiles of HFA steroidogenic enzymes are distinct from 1st to 2nd trimester, with no major differences between male and female samples. The intra-adrenal steroid hormone concentrations confirms that cortisol is produced throughout 1st and 2nd trimester, suggesting continued regulation of the HPA axis during this entire period.