Regulation of nitric oxide synthase isoforms by estrogen in the human endometrium.
OBJECTIVE
To examine the influence of estrogen on the expression of nitric oxide synthase (NOS) isoforms in human endometrial surface epithelial cell line (HES) and primary endometrial cells.


METHODS
Laboratory-based investigation.


METHODS
Academic center.


METHODS
The expression of NOS isoform protein levels and mRNA was determined following estrogen/progesterone stimulation.


METHODS
NOS protein and mRNA levels in HES and primary endometrial cells.


RESULTS
Estradiol 17-beta (E2) induced a dose- and time-dependent increase in the expression of eNOS mRNA and protein and iNOS protein in HES cells which could be blocked by the estrogen receptor antagonist ICI 182,780. Estradiol increased the expression of eNOS mRNA and protein in primary endometrial cells. Estrogen also induced phosphorylation of eNOS which could not be blocked by ICI 182,780. Progesterone in physiologic concentrations augmented the effect of estrogen on the expression of both eNOS and peNOS but not of iNOS. ICI 182,780 in high concentrations stimulated the expression of iNOS protein while inhibiting eNOS.


CONCLUSIONS
Estradiol through a genomic mechanism stimulates the expression of NOS isoforms in endometrial derived primary and HES cells. This effect is potentiated by progesterone.
Han
Guang
G
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, LA Biomedical Institute, Torrance, California, USA.
Magee
Tom
T
Khorram
Omid
O
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects* / Q000201:enzymology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics
D004965:Estrogen Antagonists; D004967:Estrogens; D007527:Isoenzymes; D019001:Nitric Oxide Synthase