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Kristin M. Taylor1 *, M. David Stewart1 *, Allison G. Stagg1 *, David A. Ricks1 , Margaret M. Joyce1 *, Fuller W. Bazer1 *, Thomas E. Spencer1 *
Center for Animal Biotechnology and Genomics, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, College Station, TX 1
In sheep, endometrial gland development (adenogenesis) begins after birth and is a steroid- and ovary-independent process. The estrogen receptor (ER) antagonist ICI182,870 retards endometrial adenogenesis in neonatal pigs, suggesting a role for ligand-independent activation of ER by growth factors via the mitogen-activated protein kinase (MAPK) signaling cascade. The present study determined temporal and spatial alterations in expression of receptors for progesterone (PR), estrogen (ER-a) and prolactin (PRL-R) during the period of endometrial gland development in neonatal ewes. Newborn ewe lambs (n=3/day) were hysterectomized on either Day 1, 7 or 14 after birth (Day 0). The uterus was fixed in 4% paraformaldehyde and analyzed for receptor gene expression by in situ hybridization and immunohistochemistry. In Day 1 uteri, endometrial glands were absent. PR expression was detected in lumenal epithelium (LE), and both ER and PR expression were detected in myometrium (MYO) and stroma (ST). In Days 7 and 14 uteri, endometrial glands were present and expressed ER, PR and PRL-R, whereas only ER and PR expression was detected in LE, ST and MYO. PRL-R expression was exclusively restricted to nascent glands and greater on Day 14 than Day 7. As compared to other uterine cell types, the new glands expressed very high levels of PR that could be indicative of activated, functional ER. These results support the hypothesis that ovine endometrial adenogenesis involves PRL binding to PRL-R in nascent endometrial glands to activate the MAPK signaling cascade and ER in a ligand-independent manner. In other cell types, activation of these pathways increase cell proliferation and differentiation. Supported in part by USDA Grant 98-35203-6322.
This abstract is being presented on Tuesday, August 3 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.