Modulation of 11 beta-hydroxysteroid dehydrogenase type 2 activity in Ishikawa cells is associated with changes in cellular proliferation

Molecular and Cellular Endocrinology
K Koyama, Z Krozowski

Abstract

An important determinant of the potency of steroid hormones is the presence of activating and inactivating enzymes in target cells. The 11 beta-hydroxysteroid dehydrogenase type 1 and type 2 enzymes (11 beta HSD1 and 11 beta HSD2) modulate glucocorticoid action and may be important in regulating cellular growth. In the present study we examined 11 beta-hydroxysteroid dehydrogenase in Ishikawa endometrial cancer cells to see if modulation of enzyme activity could potentiate the antiproliferative effects of glucocorticoids. Ishikawa cells contain an NAD dependent enzyme migrating at 41 kDa on Western blots, consistent with the presence of the glucocorticoid-inactivating enzyme 11 beta HSD2, while the NADP dependent 11 beta HSD1 is barely detectable. Given that glucocorticoids decrease cellular proliferation we asked whether inhibition of 11 beta HSD2 could further enhance this effect. Cultivation of cells in the presence of 1 microM cortisol resulted in an elevation of 11 beta HSD2 and this was associated with a decrease in cell number. Enzyme activity and cell proliferation showed a biphasic response to the synthetic anti-progestin and anti-glucocorticoid RU38486, with < or =10 nM exerting agonistic effects and > or =100 nM prod...Continue Reading

References

Dec 1, 1992·The Journal of Steroid Biochemistry and Molecular Biology·C F Holinka, E Gurpide
Nov 1, 1994·Molecular and Cellular Endocrinology·A L AlbistonZ S Krozowski
May 1, 1997·Journal of the Society for Gynecologic Investigation·W B KowalskiR T Chatterton
Mar 13, 1999·The Journal of Clinical Investigation·Y KotelevtsevJ J Mullins

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Citations

Aug 29, 2003·The Journal of Steroid Biochemistry and Molecular Biology·E H RabbittM Hewison
Aug 30, 2003·Trends in Endocrinology and Metabolism : TEM·Elizabeth A Walker, Paul M Stewart
Jun 17, 2008·Human Reproduction Update·Anthony E Michael, Aris T Papageorghiou
Jan 13, 2006·Molecular and Cellular Endocrinology·Sarah E McDonaldJ Ian Mason
Sep 15, 2005·Redox Report : Communications in Free Radical Research·Mukesh Kumar AgarwalMohammad Athar
Apr 29, 2006·Gynecologic and Obstetric Investigation·Tsatsas ManolisOvadia Abulafia
Aug 1, 2013·Physiological Reviews·Karen ChapmanJonathan Seckl
May 25, 2004·Journal of Cellular Biochemistry·Marisa Laura ZallocchiMaría Cristina Damasco
Sep 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daria KupczykAlina Woźniak

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