Alternative (backdoor) androgen production and masculinization in the human fetus
Fig 3
Levels of steroid intermediates involved in the canonical and backdoor synthesis of DHT in male fetal tissues.
Tissue levels of steroids (measured by LC-HRMS) from the placenta and fetal liver (n = 20; placentas and fetal livers were from the same pregnancies), fetal adrenal (n = 30), and fetal testis (n = 10 [for DHEA and androsterone] or 25 [for all other steroids]) are shown as individual points in each graph and arranged in the pathways shown in Fig 1. Levels of 17α-hydroxylated intermediates were not measured in this part of the study. The number of samples that were ND for each steroid are shown and, where appropriate, the LOD is shown as a red dotted line. Data shown in gray were above the LOD but below the formal LOQ, which means that the quantified data shown for these samples are less reliable. The LOD for each sample (in ng/mg tissue) depended on the mass of tissue extracted, and the lines drawn are based on the average mass of each tissue used. Green arrows indicate that the relevant enzymes are detectable (as mRNA transcripts) in that tissue, while red arrows indicate that the presumed enzyme is not detectable (based on data in Fig 4). Raw data are shown in S1 Data (Sheet 2). androstanediol, 5α-androstan-3α, 17β-diol; androstanedione, 5α-androstane-3,17-dione; androstenediol, androst-5-ene-3β,17β-diol; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone; LC-HRMS, liquid chromatography–high-resolution mass spectrometry; LOD, limit of detection; LOQ, limit of quantification; ND, nondetectable; 5αDHP, 5α-dihydroprogesterone; 17OHDHP, 17α-hydroxydihydroprogesterone.