Cigarette smoke inhibits endometrial epithelial cell proliferation through a nitric oxide-mediated pathway.
OBJECTIVE
To determine the direct effects of cigarette smoke (CS) on human endometrial surface epithelial cell line proliferation.


METHODS
In vitro study using HES cells and primary human endometrial cells.


METHODS
University-based academic center.


METHODS
Premenopausal women in the proliferative phase of the cycle.


METHODS
The HES cells and primary human endometrial cells were exposed to cigarette smoke-saturated solution.


METHODS
Cell proliferation and expression of different isoforms of nitric oxide synthase.


RESULTS
Cigarette smoke inhibited HES cell proliferation in a dose- and time-dependant manner. The inhibitory effect of CS was blocked by hemoglobin and enhanced by L-arginine (L-Arg). Cigarette smoking and nicotine stimulated the expression of endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) whereas benzo[a]pyrene (BP) only stimulated the expression of eNOS in HES cells. Cigarette smoke stimulated the expression of eNOS/iNOS in primary human endometrial cells, comprised of epithelial and stromal cells. The effect of CS on eNOS/iNOS expression in HES cells was blocked by ascorbic acid but not by glutathione.


CONCLUSIONS
Cigarette smoke inhibits endometrial cell proliferation through a nitric oxide-mediated pathway.
Khorram
Omid
O
Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Torrance, California, USA. okhorram@obgyn.humc.edu
Han
Guang
G
Magee
Thomas
T
D000975:Antioxidants / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005498:Follicular Phase; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D009538:Nicotine / Q000633:toxicity; D018722:Nicotinic Agonists / Q000633:toxicity; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017697:Premenopause; D015398:Signal Transduction / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors; D014026:Nicotiana
D000975:Antioxidants; D006454:Hemoglobins; D018722:Nicotinic Agonists; D012906:Smoke; D009569:Nitric Oxide; D001564:Benzo(a)pyrene; D009538:Nicotine; D001120:Arginine; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione; D001205:Ascorbic Acid