Glucocorticoid and progestin regulation of eosinophil chemotactic factor and complement C3 in the estrogen-treated rat uterus.
To study the steroid regulation of estradiol-induced uterine eosinophil chemotactic factor activity (ECF-U) in the rat, we injected immature female rats with combinations of estradiol, dexamethasone, progesterone, and the antihormones RU-486 and ketoconazole. An in vitro chemotactic system using blind well chambers and employing eosinophil-differentiated HL-60 promyelocytic cells was used as a bioassay for ECF-U activity. Dexamethasone and progesterone both antagonized the effects of estradiol on stimulation of ECF-U activity; neither hormone induced ECF-U activity when given alone. RU-486 and ketoconazole were able to block the inhibitory effects of dexamethasone and progesterone. The effects of dexamethasone and progesterone appear to be mediated through their specific nuclear receptors and are not due to direct effects on the chemotactic cell. Comparison of the steroid regulation of ECF-U activity with the estradiol-induced synthesis and secretion of complement component C3 showed that progesterone antagonized the effects of estradiol in both systems, whereas dexamethasone was antagonistic on ECF-U, but not on the secretion of C3. Taken together these results suggest that estradiol's effects in the rat uterus may be modulated by other steroids in at least two systems, bringing into question the common practice of studying uterine steroid actions by evaluation of a single protein or mRNA.
Howe
R S
RS
Department of Obstetrics and Gynecology, University of Pennsylvania, School of Medicine, Philadelphia 19104.
Lee
Y H
YH
Fischkoff
S A
SA
Teuscher
C
C
Lyttle
C R
CR
D000818:Animals; D001681:Biological Assay; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003176:Complement C3 / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology*; D004804:Eosinophils / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology; D008222:Lymphokines / Q000096:biosynthesis*; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D003176:Complement C3; D008222:Lymphokines; C022227:eosinophil stimulating promoter; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D003907:Dexamethasone; D007654:Ketoconazole