Cortisol-metabolizing systems in hepatocellular carcinoma and adjacent liver tissues

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 358-380-Steroid Hormone Biosynthesis & Metabolism
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-361
Tomoatsu Mune*1, Tetsuya Suwa2, Shinji Osada2, Masashi Shimoda1, Shinji Kamei1, Mitsuru Hashiramoto1, Jun Takeda2, Kazuhiro Yoshida2 and Kohei Kaku1
1Kawasaki Medical School, 2Gifu University
11β-Hydroxysteroid dehydrogenase (11βHSD) type 1, which acts as a reductase catalyzing the conversion of inactive cortisone to active cortisol, is expressed ubiquitously but especially abundant in liver. In order to display its ability as the local enhancer of glucocorticoid action, hexose-6-phosphate dehydrogenase (H6PD) is required as coenzyme-supplying system, and C/EBPα plays as a transcriptional regulator. On the one hand, 11βHSD type 2, the different isozyme inactivating cortisol, is mainly localized in the mineralocorticoid target tissues and not detected in the normal liver. However, the ectopic expression of 11βHSD type 2 is often reported in tumors derived from other organs. Changes in the expression levels of 11βHSD isozymes alter the local environment of intracellular GC availability and might significantly affect a variety of biological processes such as cell proliferation.

We analyzed mRNA expression levels of 11βHSD type 2, 11βHSD type 1, H6PD and C/EBPα in hepatocellular carcinoma (HCC) and non-cancerous liver tissue (N) derived from 15 patients with HCC, using real-time RT-PCR with normalization for GAPDH expression. Further, we evaluated their association with clinical parameters.

11βHSD type 2 was detected only in 2 (0.0002 and 0.0059) out of 15 N. However, 11βHSD type 2 expression was confirmed in 14 cases out of 15 HCC with mRNA levels of 0.054 ± 0.008 (mean ± SE). Although the expression level in HCC was about a few tenths of those seen in renal tissues that should have abundant expression, the ectopic expression in HCC has been confirmed. 11βHSD type 1 mRNA levels were 3.06 ± 0.58 in HCC vs. 2.97 ± 0.71 in N, with no significant difference. In contrast, H6PD expression in HCC (2.08 ± 0.71) was significantly higher than in N (0.61 ± 0.18), and C/EBPα expression in HCC (0.163 ± 0.04) was also higher than in N (0.06 ± 0.02). Regarding the clinical data, the expression of 11βHSD type 1 in non-cancerous part was negatively correlated with ICG retention rate at 15 minutes, the indicator of hepatic functional reserve. In addition, negative correlations were found between the 11βHSD type 2 expression level in HCC and the number of platelets or white blood cells.

Thus, cortisol inactivation by 11βHSD type 2 is enhanced in the cytoplasm of HCC cells, which might be associated with the severity of hypersplenism. While increased expression of H6PD and C/EBPα was seen in the cancer portion, the 11βHSD type 1 expression did not differ. However, the expression level of 11βHSD type 1 in the non-cancer portion might be associated with functional hepatic reserve.

Nothing to Disclose: TM, TS, SO, MS, SK, MH, JT, KY, KK

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