scholarly journals The AF-1 Activation Function of Estrogen Receptor α Is Necessary and Sufficient for Uterine Epithelial Cell Proliferation In Vivo

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2222-2233 ◽  
Author(s):  
Anne Abot ◽  
Coralie Fontaine ◽  
Isabelle Raymond-Letron ◽  
Gilles Flouriot ◽  
Marine Adlanmerini ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Epithelial Cell ◽  
Gene Transcription ◽  
Crucial Role ◽  
Estrogen Receptor Α ◽  
Epithelial Cell Proliferation ◽  
Wild Type

Abstract Estrogen receptor-α (ERα) regulates gene transcription through the 2 activation functions (AFs) AF-1 and AF-2. The crucial role of ERαAF-2 was previously demonstrated for endometrial proliferative action of 17β-estradiol (E2). Here, we investigated the role of ERαAF-1 in the regulation of gene transcription and cell proliferation in the uterus. We show that acute treatment with E2 or tamoxifen, which selectively activates ERαAF-1, similarly regulate the expression of a uterine set of estrogen-dependent genes as well as epithelial cell proliferation in the uterus of wild-type mice. These effects were abrogated in mice lacking ERαAF-1 (ERαAF-10). Four weeks of E2 treatment led to uterine hypertrophy and sustained luminal epithelial and stromal cell proliferation in wild-type mice, but not in ERαAF-10 mice. However, ERαAF-10 mice still presented a moderate uterine hypertrophy essentially due to a stromal edema, potentially due to the persistence of Vegf-a induction. Epithelial apoptosis is largely decreased in these ERαAF-10 uteri, and response to progesterone is also altered. Finally, E2-induced proliferation of an ERα-positive epithelial cancer cell line was also inhibited by overexpression of an inducible ERα isoform lacking AF-1. Altogether, these data highlight the crucial role of ERαAF-1 in the E2-induced proliferative response in vitro and in vivo. Because ERαAF-1 was previously reported to be dispensable for several E2 extrareproductive protective effects, an optimal ERα modulation could be obtained using molecules activating ERα with a minimal ERαAF-1 action.

scholarly journals Estrogen Receptor (ER)-β Reduces ERα-Regulated Gene Transcription, Supporting a “Ying Yang” Relationship between ERα and ERβ in Mice

2003 ◽  
Vol 17 (2) ◽  
pp. 203-208 ◽  
Author(s):  
Marie K. Lindberg ◽  
Sofia Movérare ◽  
Stanko Skrtic ◽  
Hui Gao ◽  
Karin Dahlman-Wright ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Gene Transcription ◽  
Physiological Role ◽  
Estrogen Receptor Α ◽  
Mrna Levels ◽  
Wild Type ◽  
Ovariectomized Mice ◽  
Adult Bone

Abstract Estrogen is of importance for the regulation of adult bone metabolism. The aim of the present study was to determine the role of estrogen receptor-β (ERβ) in vivo on global estrogen-regulated transcriptional activity in bone. The effect of estrogen in bone of ovariectomized mice was determined using microarray analysis including 9400 genes. Most of the genes (95% = 240 genes) that were increased by estrogen in wild-type (WT) mice were also increased by estrogen in ERβ-inactivated mice. Interestingly, the average stimulatory effect of estrogen on the mRNA levels of these genes was 85% higher in ERβ-inactivated than in WT mice, demonstrating that ERβ reduces estrogen receptor-α (ERα)-regulated gene transcription in bone. The average stimulatory effect of estrogen on estrogen-regulated bone genes in ERα-inactivated mice was intermediate between that seen in WT and ERαβ double-inactivated mice. Thus, ERβ inhibits ERα-mediated gene transcription in the presence of ERα, whereas, in the absence of ERα, it can partially replace ERα. In conclusion, our in vivo data indicate that an important physiological role of ERβ is to modulate ERα-mediated gene transcription supporting a “Ying Yang” relationship between ERα and ERβ in mice.

scholarly journals Juxtacrine Activity of Estrogen Receptor α in Uterine Stromal Cells is Necessary for Estrogen-Induced Epithelial Cell Proliferation

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Wipawee Winuthayanon ◽  
Sydney L. Lierz ◽  
Karena C. Delarosa ◽  
Skylar R. Sampels ◽  
Lauren J. Donoghue ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Epithelial Cell ◽  
Stromal Cells ◽  
Estrogen Receptor Α ◽  
Epithelial Cell Proliferation

scholarly journals Neonatal Estrogen Receptor β Is Important in the Permanent Inhibition of Epithelial Cell Proliferation in the Mouse Uterus

Endocrinology ◽  
2015 ◽  
Vol 156 (9) ◽  
pp. 3317-3328 ◽  
Author(s):  
Tadaaki Nakajima ◽  
Yuki Tanimoto ◽  
Masami Tanaka ◽  
Pierre Chambon ◽  
Hajime Watanabe ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Epithelial Cell ◽  
Kinase Inhibitor ◽  
Estrogen Receptor Α ◽  
Epithelial Cell Proliferation ◽  
Cyclin Dependent Kinase ◽  
Mouse Uterus ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Old Mice

Estrogen receptor α (ERα) plays a pivotal role in the mouse uterine and vaginal epithelial cell proliferation stimulated by estrogen, whereas ERβ inhibits cell proliferation. ERβ mRNA is expressed in neonatal uteri and vaginae; however, its functions in neonatal tissues have not been ascertained. In this study, we investigated the ontogenic mRNA expression and localization of ERβ, and its roles in cell proliferation in neonatal uteri and vaginae of ERβ knockout (βERKO) mice. ERβ mRNA and protein were abundant in the uterine and vaginal epithelia of 2-day-old mice and decreased with age. In uterine and vaginal epithelia of 2-day-old βERKO mice, cell proliferation was greater than that in wild-type animals and in uterine epithelia of 90- and 365-day-old βERKO mice. In addition, p27 protein, known as a cyclin-dependent kinase inhibitor, was decreased in the uteri of 90- and 365-day-old βERKO mice. Inhibition of neonatal ERs by ICI 182780 (an ER antagonist) treatment stimulated cell proliferation and decreased p27 protein in the uterine luminal epithelium of 90-day-old mice but not in the vaginal epithelium. These results suggest that neonatal ERβ is important in the persistent inhibition of epithelial cell proliferation with accumulation of p27 protein in the mouse uterus. Thus, suppression of ERβ function in the uterine epithelium during the neonatal period may be responsible for a risk for proliferative disease in adults.

Ontogeny of cell proliferation and DNA synthesis in rat colon: role of glucocorticoids

1983 ◽  
Vol 244 (5) ◽  
pp. G469-G474 ◽  
Author(s):  
J. P. Buts ◽  
R. De Meyer ◽  
J. Kolanowski
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Dna Synthesis ◽  
Mitotic Index ◽  
Dna Content ◽  
Thymidine Incorporation ◽  
Rat Colon ◽  
Epithelial Cell Proliferation ◽  
New Findings

This study was undertaken to determine whether the rat colon exhibits ontogenic changes in epithelial cell proliferation and DNA synthesis during growth. DNA synthesis was measured at intervals after birth in four colonic segments by the incorporation rates of [3H]thymidine. The labeled crypt cell index was determined by radioautography. New findings from our study are that 1) in each colonic segment of suckling rats, [3H]thymidine incorporation rate overshot the adult levels (49-119%) with a peak occurring at day 14 postpartum, 2) between days 14 and 20, the incorporation rates declined sharply to adult values and remained thereafter unchanged until adulthood; during the same period, the labeled and mitotic index decreased, respectively, from 52 to 19% and from 3.58 to 1.43%, 3) the decrease in DNA synthesis and in cell proliferation rates was concomitant with an upsurge in plasma total corticosterone initiated on day 14, and 4) treatment of 10-day-old sucklings with physiological doses of hydrocortisone for 4 consecutive days significantly depressed (P less than 0.01) colonic DNA content and DNA synthesis rates to levels about 45-67% of the control values. These data indicate that growth of the colon may be under the control of glucocorticoid secretion at the weaning period.

Proliferation and repair of guinea pig tracheal epithelium after neuropeptide depletion and injury in vivo

1997 ◽  
Vol 273 (6) ◽  
pp. L1235-L1241 ◽  
Author(s):  
John S. Kim ◽  
Valerie S. McKinnis ◽  
Kimberly Adams ◽  
Steven R. White
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mucosal Injury ◽  
Nuclear Antigen ◽  
Airway Epithelial ◽  
Epithelial Cell Proliferation ◽  
Injury Site ◽  
And Migration

Neuropeptides stimulate airway epithelial cell proliferation and migration in vitro, but the role of neuropeptides in the repair of the epithelium after injury in vivo is not clear. We studied epithelial proliferation and repair in 83 male Hartley guinea pigs. Animals received capsaicin weekly for 3 wk to deplete airway neuropeptides. One week later, the dorsal aspect of the trachea was injured with a metal stylette. Animals were killed 1 h to 1 wk later, after which epithelial cell proliferation was assessed for the presence of proliferating cell nuclear antigen (PCNA). PCNA labeling was <3% in noninjured animals. PCNA labeling increased substantially in the first 72 h after injury in control animals but was significantly decreased in capsaicin-treated animals within and adjacent to the site of injury. PCNA labeling increased opposite to the injury site in both control and capsaicin animals over the first 72 h. We conclude that neuropeptide depletion significantly attenuates both epithelial cell proliferation and repair in the first 72 h after mechanical injury to the trachea. However, neuropeptide depletion did not slow the ultimate repair of tracheal mucosal injury. Proliferation of epithelial cells in response to injury occurs throughout the airway, even away from the injury site.

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