Effects of 17 beta-estradiol and progesterone on migration of human monocytic THP-1 cells stimulated by minimally oxidized low-density lipoprotein in vitro.
OBJECTIVE
Many epidemiological studies have shown that postmenopausal hormone replacement therapy (HRT) has a beneficial effect on atherosclerotic cardiovascular disease. The aim of this study was to investigate the effects of estrogen and progestin on the migration of monocytes induced by minimally oxidized low-density lipoprotein (m-ox-LDL) in vitro.


METHODS
Human monocytic THP-1 cells were used for the study. Migration assay was performed using a modified Boyden chamber.


RESULTS
The presence of estrogen receptors was determined in THP-1 cells by Western and Northern blot analysis. Although native LDL had no significant effects on the migration of THP-1 cells, m-ox-LDL increased the migration of THP-1 cells in a dose-dependent manner. Although 17 beta-estradiol (E2, 10(-9)-10(-6) M) inhibited the 10 micrograms/ml-induced migration of THP-1 cells in a dose-dependent manner, estrone (E1), estriol (E3) and progesterone (P) had no significant effects. The combination of P (10(-9)-10(-6) M) did not show any effect on the inhibitory effect of 10(-7) M E2. Preincubation of THP-1 cells with the anti-estrogenic agent, tamoxifen (10(-6) M), significantly antagonized the inhibitory effect of 10(-7) M E2. m-ox-LDL stimulated MCP-1 secretion from THP-1 cells, which was reduced by E2. Anti-human MCP-1 neutralizing antibody inhibited the migration of THP-1 cells stimulated by m-ox-LDL. E2 also inhibited the 10 ng/ml MCP-1-induced migration of THP-1 cells in a dose-dependent manner.


CONCLUSIONS
These findings suggest that the inhibitory effect of E2 on the migration of monocytes might be one of the factors involved in the decreased incidence of atherosclerotic cardiovascular disease in premenopausal women and postmenopausal HRT.
Okada
M
M
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Suzuki
A
A
Mizuno
K
K
Asada
Y
Y
Ino
Y
Y
Kuwayama
T
T
Tamakoshi
K
K
Mizutani
S
S
Tomoda
Y
Y
D000328:Adult; D001161:Arteriosclerosis / Q000517:prevention & control; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007948:Leukemia, Monocytic, Acute; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008875:Middle Aged; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology
D004965:Estrogen Antagonists; D008077:Lipoproteins, LDL; D013629:Tamoxifen; D011374:Progesterone; D004958:Estradiol