Human Reproduction, Vol. 17, No. 7, 1709-1714,
July 2002
© 2002 European Society of Human Reproduction and Embryology
Different mechanisms for the induction of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone in human endometrial stromal cells
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1–1–1, Ube 755-8505, Japan
BACKGROUND: The present study was undertaken to investigate the cAMP-dependent regulation of copper-zinc superoxide dismutase (Cu,Zn-SOD) and manganese SOD (Mn-SOD) by ovarian steroids in human endometrial stromal cells (ESC). METHODS and RESULTS: To examine the effect of cAMP on SOD expression, ESC were incubated with dibutyryl-cAMP (db-cAMP, 0.5 mmol/l), forskolin (25 µmol/l), or estradiol (E2, 10-8 mol/l) + medroxyprogesterone acetate (MPA, 10-6 mol/l), for 18 days. E2 + MPA significantly increased Cu,Zn-SOD activity and mRNA concentrations, whereas db-cAMP and forskolin had no effect. On the other hand, Mn-SOD activity and mRNA concentration were significantly increased by all of these treatments. Insulin-like growth factor-binding protein-1, a marker of decidualization, was clearly induced by db-cAMP, forskolin or E2 + MPA, accompanied by morphological changes characteristic of decidualization. To study whether the increase in Mn-SOD by db-cAMP or E2 + MPA was mediated by cAMP-dependent protein kinase A (PKA), ESC were incubated with protein kinase inhibitor (PKI) (10 µg/ml), an inhibitor of PKA, in the presence of db-cAMP or E2 + MPA. The increase in Mn-SOD activity following db-cAMP or E2 + MPA was completely inhibited by PKI. CONCLUSIONS: In the process of decidualization, E2 + MPA increases Mn-SOD expression via a cAMP-dependent pathway. Cu,Zn-SOD is also up-regulated by E2 + MPA, but via a different pathway from that involving cAMP.
Key words: cAMP/endometrial stromal cell/progesterone/superoxide dismutase
1 To whom correspondence should be addressed. E-mail: obgyn{at}po.cc.yamaguchi-u.ac.jp
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