Different mechanisms for the induction of copper-zinc superoxide dismutase and manganese superoxide dismutase by progesterone in human endometrial stromal cells

Author： Sugino Norihiro Karube-Harada Ayako Sakata Aki Takiguchi Shuji Kato Hiroshi

Publisher： Oxford University Press

ISSN： 1460-2350

Source： Human Reproduction, Vol.17, Iss.7, 2002-07, pp. : 1709-1714

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Abstract

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 mol/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 g/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.