Combined Liquid Chromatography–Tandem Mass Spectrometry Analysis of Progesterone Metabolites
Fig 1
Proposed progesterone metabolism in human endometrium.
Progesterone is metabolized by 20-ketosteroid reductases and 5α-reductases, to form (20S/R)-pregn-4-ene-3α,20-diol and 5α-pregnane-3,20-dione. Reductions of the 3-keto and 20-keto groups are catalysed by the aldo-keto reductases AKR1C1-AKR1C3. Here, AKR1C1-AKR1C3 can act on the 20-keto group of pregn-4-enes, and they can reduce both 3-keto and 20-keto groups of 5α-pregnanes. The progesterone (20S)-pregn-4-ene-3α,20-diol formed by the AKR1C enzymes can be oxidized back to progesterone by the 20α-hydroxysteroid dehydrogenase activity of 17β-hydroxysteroid dehydrogenase type 2 (HSD17B2). The formation of 5α-pregnanes is irreversible and is catalysed by 5α-reductases types 1 (SRD5A1) and 2 (SRD5A2) [35–37].