Androgenic and estrogenic 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase in human ovarian epithelial tumors: evidence for the type 1, 2 and 5 isoforms

The diversity of sex steroid action: novel functions of hydroxysteroid (17β) dehydrogenases as revealed by genetically modified mouse models

“…It has also been shown that ovarian serous borderline tumours are positively associated with a history of PCOS, thus with a history of (foetal) hyperandrogenism (Olsen et al 2008). HSD17B1 expression has been linked to ovarian epithelial cancers and was shown to positively correlate with an increasing malignancy of ovarian surface epithelial tumours (Sasano et al 1996, Blomquist et al 2002, Chura et al 2009). Both estrogens and androgens have been associated with ovarian epithelial carcinogenesis (Syed et al 2001, Ho 2003.…”

A useful cell system for studying the regulation of 17HSD/KSR type 2 activity and expression in ovarian epithelial cancer

“…Our group has presented kinetic evidence of an androgenic form of 17HSD/KSR in the CAOV-3 and OVCAR-3 cell lines derived from an ovarian adenocarcinoma but there was no evidence of estrogenic type 1 isoform [18]. In addition, activity in these cell lines was low when compared with levels we subsequently observed in samples of epithelial tumor tissue [19,20] suggestive of the possibility that activity may be lost in cell lines established from primary tumors. As has been pointed out, one possible confounding factor may be that many of the current cell lines were established from patients exposed to radiation and or chemotherapy [21].…”

“…17HSD/KSR and 3␣-HSD/KSR activities were assayed as described previously [19,24]. Briefly, 10-l aliquots of sample were combined with 10 l of reaction mixture to give a 20-l reaction mixture containing 1.0 M 3 H-labeled steroid substrate, 0.5 mM pyridine nucleotide cofactor and 0.04 M buffer.…”

Design, chemical synthesis and biological evaluation of 3-spiromorpholinone/3-spirocarbamate androsterone derivatives as inhibitors of 17β-hydroxysteroid dehydrogenase type 3

“…31 In brief, rat testes were homogenized on ice with a Polytron in cold phosphate buffer (20 mM KH 2 PO 4 , 0.25 M sucrose, 1 mM EDTA, pH 7.5) containing protease inhibitors mini-complete (Roche Diagnostics, Laval, QC, Canada) and the mixture was centrifuged at 12,500g for 15 min to remove the mitochondria, plasma membranes, and cell fragments. The supernatant was further centrifuged at 100,000g for 45 min using an ultracentrifuge equipped with a 70.1 Ti rotor.…”