Endometrial cancer (EC) is one of the most common gynecological
malignancies worldwide. It is associated with prolonged exposure to
estrogens that is unopposed by the protective effects of
progesterone, which suggests that altered
progesterone biosynthesis, metabolism and actions might be implicated in the development of EC. Our aim was to evaluate these processes through quantitative real-time PCR expression analysis in up to 47 pairs of EC tissue and adjacent control endometrium. First, we examined the expression of genes encoding
proteins associated with
progesterone biosynthesis:
steroidogenic acute regulatory protein (STAR); a side chain cleavage
enzyme (
CYP11A1); and 3β-hydroxysteroid
dehydrogenase/ketosteroid
isomerase (HSD3B). There were 1.9- and 10.0-fold decreased expression of STAR and
CYP11A1, respectively, in EC versus adjacent control endometrium, with no significant differences in the expression of HSD3B1 and
HSD3B2. Next, we examined expression of genes encoding five
progesterone metabolizing
enzymes: the 3-keto and 20-ketosteroid
reductases (AKR1C1-AKR1C3) and 5α-reductases (SRD5A1 and SRD5A2); and the opposing 20α-hydroxysteroid
dehydrogenase (HSD17B2). These genes are expressed in EC and adjacent control endometrium. No statistically significant differences were seen in
mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1. Expression of HSD17B2 was 3.0-fold increased, and expression of SRD5A2 was 3.7-fold decreased, in EC versus adjacent control endometrium. We also examined
mRNA levels of
progesterone receptors A and B (PGR), and separately the expression of
progesterone receptor B (PR-B). Here we saw 1.8- and 2.0-fold lower
mRNA levels of PGR and PR-B, respectively, in EC versus adjacent control endometrium. This down-regulation of STAR,
CYP11A1 and PGR in
endometrial cancer may lead to decreased
progesterone biosynthesis and actions although the effects on
progesterone levels should be further studied.