Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/8055
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Type: Journal article
Title: Ovarian steroid hormones regulate granulocyte-macrophage colony-stimulating factor synthesis by uterine epithelial cells in the mouse
Author: Robertson, S.
Mayrhofer, G.
Seamark, R.
Citation: Biology of Reproduction, 1996; 54(1):183-196
Publisher: SOC STUDY REPRODUCTION
Issue Date: 1996
ISSN: 0006-3363
1529-7268
Abstract: Uterine epithelial cells have been shown by in vitro studies to be a potent source of the inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), and the luminal and glandular epithelium has been confirmed as the predominant site of GM-CSF expression in the intact endometrium by in situ hybridization. To examine the role of ovarian steroid hormones in GM-CSF synthesis, GM-CSF bioactivity has been measured in the supernatants of short-term primary cultures of endometrial cells prepared from mice in which steroid levels were perturbed by ovariectomy and steroid replacement or by steroid antagonists. GM-CSF production was found to fluctuate in cells harvested at different times during the estrous cycle, peaking at estrus. Endometrial cells derived from ovariectomized mice produced 25-fold less GM-CSF than did cells from estrous mice, and production was increased if ovariectomized mice were pretreated with estrogen, but not progesterone, 3 h or more before harvest. This estrogen-induced increase was inhibited by coadministration of progesterone or by induction of a decidual response and was blocked by the estrogen antagonist ZK 119,010. By contrast, pretreatment of mice with the anti-progestin RU486 significantly elevated GM-CSF output in cells from ovariectomized mice given estrogen and progesterone in combination and antagonized the inhibition of GM-CSF release seen in cells harvested from mice treated with hCG. These studies demonstrate that GM-CSF synthesis and/or release by uterine epithelial cells is stimulated by estrogen, with progesterone having a moderate inhibitory effect. Analysis of GM-CSF mRNA expression in uterine epithelial cell cultures and in intact uteri from steroid hormone-treated ovariectomized mice by quantitative reverse transcription-polymerase chain reaction indicated that the effects of estrogen and progesterone on GM-CSF release are mediated at least in part at the transcriptional level. These findings implicate GM-CSF as a local mediator of steroid-driven remodeling events in the cycling and preimplantation endometrium, possibly acting through the recruitment and behavioral regulation of granulocytes and macrophages.
Keywords: Ovary; Uterus; Decidua; Epithelium; Animals; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice; Estradiol; Progesterone; Chorionic Gonadotropin; Granulocyte-Macrophage Colony-Stimulating Factor; RNA, Messenger; Ovariectomy; In Situ Hybridization; Estrus; Kinetics; Female
RMID: 0030005311
DOI: 10.1095/biolreprod54.1.183
Appears in Collections:Obstetrics and Gynaecology publications

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