The stimulation of uterine complement component C3 gene expression by antiestrogens.
We have previously demonstrated that complement component C3 is regulated by estradiol in the rat uterus. The antiestrogens tamoxifen, LY117018, and LY156758 exert both agonist and antagonist effects on the immature rat uterus. In this study, these three antiestrogens also stimulated an increase in the synthesis and secretion of C3. The combination of LY117018 and estradiol did not increase C3 to a greater extent than LY117018 alone, which suggests a similar mechanism of regulation. The regulation may be transcriptional since both estradiol and tamoxifen increase the concentration of C3 mRNA. Results of in situ hybridization revealed that the increase in C3 mRNA occurred in the luminal epithelial cells. Although the induction by estradiol and the antiestrogens was similar in most aspects, the time course for tamoxifen-stimulated synthesis differed from estradiol in that the time required to achieve maximal concentrations of C3 was delayed by 12 h with tamoxifen. This pattern did not appear to be related to the time it took to convert tamoxifen to 4-hydroxytamoxifen since the C3 response for these antiestrogens were identical. The antiestrogen-stimulated increase in C3 synthesis and mRNA concentration was prevented by the co-administration of progesterone lending support to the hypothesis that the antiestrogens regulate C3 synthesis via a mechanism similar to estrogen.
Sundstrom
S A
SA
Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia 19104.
Komm
B S
BS
Xu
Q
Q
Boundy
V
V
Lyttle
C R
CR
D000818:Animals; D003176:Complement C3 / Q000235:genetics* / Q000378:metabolism; D004347:Drug Interactions; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D010880:Piperidines / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020849:Raloxifene Hydrochloride; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014599:Uterus / Q000378:metabolism*
D003176:Complement C3; D004965:Estrogen Antagonists; D010880:Piperidines; D011759:Pyrrolidines; D012333:RNA, Messenger; D013876:Thiophenes; D013629:Tamoxifen; D020849:Raloxifene Hydrochloride; D011374:Progesterone; D004958:Estradiol; C025430:LY 117018