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


RESULTS
To examine the effect of cAMP on SOD expression, ESC were incubated with dibutyryl-cAMP (db-cAMP, 0.5 mmol/l), forskolin (25 micromol/l), or estradiol (E(2), 10(-8) mol/l) + medroxyprogesterone acetate (MPA, 10(-6) mol/l), for 18 days. E(2) + 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 E(2) + MPA, accompanied by morphological changes characteristic of decidualization. To study whether the increase in Mn-SOD by db-cAMP or E(2) + MPA was mediated by cAMP-dependent protein kinase A (PKA), ESC were incubated with protein kinase inhibitor (PKI) (10 microg/ml), an inhibitor of PKA, in the presence of db-cAMP or E(2) + MPA. The increase in Mn-SOD activity following db-cAMP or E(2) + MPA was completely inhibited by PKI.


CONCLUSIONS
In the process of decidualization, E(2) + MPA increases Mn-SOD expression via a cAMP-dependent pathway. Cu,Zn-SOD is also up-regulated by E(2) + MPA, but via a different pathway from that involving cAMP.
Sugino
Norihiro
N
Department of Obstetrics and Gynecology, Yamaguchi University School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan. obgyn@po.cc.yamaguchi-u.ac.jp
Karube-Harada
Ayako
A
Sakata
Aki
A
Takiguchi
Shuji
S
Kato
Hiroshi
H
D000328:Adult; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D003656:Decidua / Q000502:physiology; D004338:Drug Combinations; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D004790:Enzyme Induction; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D008875:Middle Aged; D011374:Progesterone / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects* / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D004338:Drug Combinations; D045167:Progesterone Congeners; D011374:Progesterone; D004958:Estradiol; D003994:Bucladesine; D017258:Medroxyprogesterone Acetate; D000242:Cyclic AMP; D013482:Superoxide Dismutase