Nitric oxide mediates inhibitory effect of interleukin-1beta on estrogen production in human granulosa-luteal cells.
OBJECTIVE
To investigate the effect of IL-1beta on NO production and steroidogenesis in human granulosa-luteal cells obtained from women undergoing in vitro fertilization procedures.


METHODS
To investigate the effect of IL-1beta, granulosa-luteal cells were cultured with various doses of IL-1beta (0, 0.05, 0.5, 5, 50, 100 ng/ml), IL-1beta (5 ng/ml) with NG-nitro-L-arginine-methyl ester (L-NAME), selective inhibitors of NOS, sodium nitroprusside (SNP), NO donors and Genistain, a tyrosine kinase inhibitor.


RESULTS
IL-1beta induced a dose-dependent stimulation of NO production and inhibited the production of estradiol in a significant way in a dose-dependent manner. L-NAME significantly decreased NO production and increased the production of estradiol and progesterone. SNP significantly increased NO production and caused decreases in the production of both estradiol and progesterone. Genistain decreased NO production and significantly increased the production of estradiol and progesterone. Inducible NOS (iNOS) messenger RNA was present in granulosa-luteal cells before treatment with IL-1beta.


CONCLUSIONS
IL-1beta stimulated NO production, and NO inhibited the production of estradiol.
Tobai
H
H
Department of Obstetrics and Gynecology, Iwate Medical University, Japan.
Nishiya
I
I
D002478:Cells, Cultured; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D005307:Fertilization in Vitro; D006107:Granulosa Cells / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger
D017931:DNA Primers; D004965:Estrogen Antagonists; D004967:Estrogens; D007375:Interleukin-1; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II