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Figure 1 | Arthritis Research & Therapy

Figure 1

From: CYB5A polymorphism increases androgens and reduces risk of rheumatoid arthritis in women

Figure 1

Analysis of pregnenolone metabolism in rheumatoid arthritis synovial fibroblasts. (A) Pathways and enzymes of pregnenolone metabolism as identified in synovial fibroblasts (reviewed in a previous publication [29]). (B, D) Two-dimensional thin layer chromatography (2D-TLC) separation of pregnenolone and its metabolites. (B) Position of unlabeled steroid standards of identified metabolites (circles) overlaid to the 3H-image of the pregnenolone substrate used. (C) 3H-image from a GG-fibroblast line accumulating (besides compound X) 17α-hydroxy-pregnenolone, the direct product 17α-hydroxylase activity, together with 7α-hydroxy-dehydroepiandrosterone (DHEA). (D) 3H-image from an AG-fibroblast line accumulating almost exclusively 7α-hydroxy-DHEA. CYB5A, cytochrome b5, type A; CYP17A1, steroid 17α-hydroxylase/17,20-lyase (cytochrome P450 17A1). E2 was found in a minority of fibroblasts only. *Start indicates point of sample application. X indicates the major product formed from pregnenolone by fibroblasts independently from rs1790834 genotype. Arrows indicate the metabolites with production dependent on the rs1790834 genotype. CYP7B1, 25-hydroxycholesterol 7α-hydroxylase (cytochrome P450 7B1); HSD3B, 3β-hydroxysteroid dehydrogenase; Δ5Adiol, Δ5-androstenediol; Adione, androstenedione; Preg, pregnenolone; Prog, progesterone; Testo, testosterone. E2, estradiol.

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