scholarly journals Estrogen Receptor-α Signaling in Growth of the Ventral Prostate: Comparison of Neonatal Growth and Postcastration Regrowth

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4421-4427 ◽  
Author(s):  
Yoko Omoto
Keyword(s):  
Estrogen Receptor ◽  
Cyclin D1 ◽  
Branching Morphogenesis ◽  
Estrogen Receptor Α ◽  
Testosterone Replacement ◽  
Ventral Prostate ◽  
Wild Type ◽  
Fibroblast Growth Factor 10 ◽  
Ductal Branching ◽  
Stimulation Of

A role for estrogen receptor (ER)-α in branching morphogenesis in the ventral prostate (VP) has previously been demonstrated; in the VP of ERα−/− mice, there are fewer side branches than in wild-type littermates. In the present study, we show that in the postnatal VP, fibroblast growth factor 10 (FGF10) is expressed in wild-type mice but not in ERα−/− mice, and because branching involves proliferation pathways also used in malignant growth, we investigated whether branching during regrowth of the VP after castration involves ERα and FGF10. ERα was not detectable in the prostates of sham-operated or castrated mice but was expressed in the prostatic epithelium between d 3 and 5 after testosterone replacement. Blocking either ERα or ERβ with ICI 182,780 had no detectable effects on epithelial cell proliferation during regrowth by testosterone. The ERα agonist, propylpyrazoletriol, did not induce regrowth by itself, but exposure to propylpyrazoletriol on d 3–5 of testosterone replacement resulted in cyclin D1-positive cells in the ductal epithelium, invasion of FGF10-positive immune cells in the regrowing prostate, and budding 14 d later. Testosterone replacement alone did not induce cyclin D1, FGF10, or bud formation. These results indicate that stimulation of ERα is essential for ductal branching during postnatal prostate growth. During regrowth after castration, there is a window in time when selective stimulation of ERα can also induce ductal branching. The FGF10 for this growth comes from the immune system, not from the prostatic mesenchyme.

Estrogen Receptor-Independent Catechol Estrogen Binding Activity:  Protein Binding Studies in Wild-Type, Estrogen Receptor-α KO, and Aromatase KO Mice Tissues†

Biochemistry ◽  
2004 ◽  
Vol 43 (21) ◽  
pp. 6698-6708 ◽  
Author(s):  
Brian J. Philips ◽  
Pete J. Ansell ◽  
Leslie G. Newton ◽  
Nobuhiro Harada ◽  
Shin-Ichiro Honda ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Protein Binding ◽  
Estrogen Receptor Α ◽  
Binding Activity ◽  
Wild Type ◽  
Binding Studies ◽  
Catechol Estrogen ◽  
Estrogen Binding

scholarly journals Nuclear Activation Function 2 Estrogen Receptor α Attenuates Arterial and Renal Alterations Due to Aging and Hypertension in Female Mice

2020 ◽  
Vol 9 (5) ◽  
Author(s):  
Emmanuel Guivarc'h ◽  
Julie Favre ◽  
Anne‐Laure Guihot ◽  
Emilie Vessières ◽  
Linda Grimaud ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Estrogen Receptor ◽  
Angiotensin Ii ◽  
Systolic Blood Pressure ◽  
Vascular Reactivity ◽  
Nuclear Gene ◽  
Estrogen Receptor Α ◽  
Protective Effects ◽  
Wild Type ◽  
Female Mice

Background The cardiovascular protective effects of estrogens in premenopausal women depend mainly on estrogen receptor α (ERα). ERα activates nuclear gene transcription regulation and membrane‐initiated signaling. The latter plays a key role in estrogen‐dependent activation of endothelial NO synthase. The goal of the present work was to determine the respective roles of the 2 ERα activities in endothelial function and cardiac and kidney damage in young and old female mice with hypertension, which is a major risk factor in postmenopausal women. Methods and Results Five‐ and 18‐month‐old female mice lacking either ERα (ERα −/− ), the nuclear activating function AF2 of ERα (AF2°), or membrane‐located ERα (C451A) were treated with angiotensin II (0.5 mg/kg per day) for 1 month. Systolic blood pressure, left ventricle weight, vascular reactivity, and kidney function were then assessed. Angiotensin II increased systolic blood pressure, ventricle weight, and vascular contractility in ERα −/− and AF2° mice more than in wild‐type and C451A mice, independent of age. In both the aorta and mesenteric resistance arteries, angiotensin II and aging reduced endothelium‐dependent relaxation in all groups, but this effect was more pronounced in ERα −/− and AF2° than in the wild‐type and C451A mice. Kidney inflammation and oxidative stress, as well as blood urea and creatinine levels, were also more pronounced in old hypertensive ERα −/− and AF2° than in old hypertensive wild‐type and C451A mice. Conclusions The nuclear ERα‐AF2 dependent function attenuates angiotensin II–dependent hypertension and protects target organs in aging mice, whereas membrane ERα signaling does not seem to play a role.

scholarly journals Identification of a Novel Estrogen Receptor-α Variant and Its Upstream Splicing Regulator

2010 ◽  
Vol 24 (5) ◽  
pp. 914-922 ◽  
Author(s):  
Kazufumi Ohshiro ◽  
Prakriti Mudvari ◽  
Qing-chang Meng ◽  
Suresh K. Rayala ◽  
Aysegul A. Sahin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Alternative Splicing ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Α ◽  
Mrna Splicing ◽  
Human Breast ◽  
Alternative Mrna Splicing

Abstract Alternative splicing of precursor mRNA is a fundamental mechanism to generate multiple proteins from a single gene. Although constitutive and alternative mRNA splicing is temporally and spatially regulated, deregulation of mRNA splicing could cause development, progression, and metastasis of tumors. Through yeast two-hybrid screening of a human breast cDNA library using estrogen receptor-α (ERα) as bait, we identified a novel nuclear receptor box containing full-length protein, nuclear protein E3-3 (NPE3-3). Our results revealed that NPE3-3 associates with not only ERα but also with splicing factors, serine/arginine-rich protein (SRp)-30c, SRp40, and splicing factor SC-35, suggesting that NPE3-3 is likely to be involved in regulation of mRNA splicing. Accordingly, transient expression of NPE3-3 in cells resulted in expected splicing of the CD44 control minigene. We also discovered that NPE3-3-overexpressing clones produced a novel, previously unrecognized, alternatively spliced variant of ERα (termed ERαV), which had a molecular size of 37 kDa composed of only exons 1, 2, 7, and 8. ERαV was expressed and sequestered in the cytoplasm in MCF-7 cells stably overexpressing NPE3-3, suggesting its involvement in nongenomic hormone signaling. NPE3-3 clones exhibited up-regulation of ERK1/2 signaling, cyclin D1, and cathepsin D and enhanced tumor cell proliferation, migration, and tumorigenicity. Moreover, direct expression of the ERαV in breast cancer cells stimulated ERK1/2 up-regulation and cyclin D1 expression. We found that ERαV physically interacted with MAPK kinase (MEK)-1/2, and thus, an ERαV and MEK1/2 complex could lead to the activation of the ERK1/2 pathway. Interestingly, NPE3-3 was up-regulated in human breast tumors. These findings revealed a role for NPE3-3 in alternative splicing and suggest that ERα is a physiological target of NPE3-3, leading to a constitutive nongenomic signaling pathway in breast cancer cells.

scholarly journals Formation of Cystic Ovarian Follicles Associated with Elevated Luteinizing Hormone Requires Estrogen Receptor-β

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4693-4702 ◽  
Author(s):  
John F. Couse ◽  
Mariana M. Yates ◽  
Ryan Sanford ◽  
Abraham Nyska ◽  
John H. Nilson ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Ovarian Function ◽  
Ectopic Expression ◽  
Estrogen Receptor Α ◽  
Corpora Lutea ◽  
Rodent Models ◽  
Specific Enzyme ◽  
Plasma Estradiol ◽  
Lh Secretion ◽  
Stimulation Of

Abstract Stringent regulation of LH secretion from the pituitary is vital to ovarian function in mammals. Two rodent models of LH hypersecretion are the transgenic LHβ-C-terminal peptide (LHβCTP) and estrogen receptor-α (ERα)-null (αERKO) mice. Both exhibit ovarian phenotypes of chronic anovulation, cystic and hemorrhagic follicles, lack of corpora lutea, interstitial/stromal hyperplasia, and elevated plasma estradiol and testosterone. Because ERβ is highly expressed in granulosa cells of the ovary, we hypothesized the intraovarian actions of ERβ may be necessary for full manifestation of phenotypes associated with LH hyperstimulation. To address this question, we generated female mice that possess elevated LH, but lack ERβ, by breeding the LHβCTP and ERβ-null (βERKO) mice. A comparison of LHβCTP, αERKO, and βERKOLHCTP females has allowed us to elucidate the contribution of each ER form to the pathologies and endocrinopathies that occur during chronic LH stimulation of the ovary. αERKO ovaries respond to elevated LH by exhibiting an amplified steroidogenic pathway characteristic of the follicular stage of the ovarian cycle, whereas wild-typeLHCTP and βERKOLHCTP females exhibit a steroidogenic profile more characteristic of the luteal stage. In addition, the hemorrhagic and cystic follicles of the LHβCTP and αERKO ovaries require the intraovarian actions of ERβ for manifestation, because they were lacking in the βERKOLHCTP ovary. In turn, ectopic expression of the Leydig cell-specific enzyme, Hsd17b3, and male-like testosterone synthesis in the αERKO ovary are unique to this genotype and are therefore the culmination of elevated LH and the loss of functional ERα within the ovary.

scholarly journals Estrogen Stimulation of Kiss1 Expression in the Medial Amygdala Involves Estrogen Receptor-α But Not Estrogen Receptor-β

Endocrinology ◽  
2016 ◽  
Vol 157 (10) ◽  
pp. 4021-4031 ◽  
Author(s):  
Shannon B. Z. Stephens ◽  
Navdeep Chahal ◽  
Nagambika Munaganuru ◽  
Ruby A. Parra ◽  
Alexander S. Kauffman
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Β ◽  
Medial Amygdala ◽  
Estrogen Stimulation ◽  
Stimulation Of

scholarly journals Estrogen receptor-α mediates estrogen-inducible abnormalities in the developing penis

Reproduction ◽  
2007 ◽  
Vol 133 (5) ◽  
pp. 1057-1067 ◽  
Author(s):  
H O Goyal ◽  
T D Braden ◽  
P S Cooke ◽  
M A Szewczykowski ◽  
C S Williams ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Levator Ani ◽  
Estrogen Receptor Α ◽  
Control Group ◽  
Wild Type ◽  
Penile Length ◽  
In The Wild ◽  
Os Penis ◽  
Harmful Effects ◽  
Wild Type Control

Previously, we reported an association between estrogen receptor-α (ERα) upregulation and detrimental effects of neonatal diethylstilbestrol (DES) exposure in the rat penis. The objective of this study was to employ the ERα knockout (ERαKO) mouse model to test the hypothesis that ERα mediates DES effects in the developing penis. ERαKO and wild-type C57BL/6 mice received oil or DES at a dose of 0.2 μg/pup per day (0.1 mg/kg) on alternate days from postnatal days 2 to 12. Fertility was tested at 80–240 days of age and tissues were examined at 96–255 days of age. DES caused malformation of the os penis, significant reductions in penile length, diameter, and weight, accumulation of fat cells in the corpora cavernosa penis, and significant reductions in weight of the bulbospongiosus and levator ani muscles in wild-type mice. Conversely, ERαKO mice treated with DES developed none of the above abnormalities. While nine out of ten male mice sired pups in the wild-type/control group, none did in the wild-type/DES group. ERαKO mice, despite normal penile development, are inherently infertile. Both plasma and intratesticular testosterone levels were unaltered in the DES-treated wild-type or DES-treated ERαKO mice when compared with controls, although testosterone concentration was much higher in the ERαKO mice. Hence, the resistance of ERαKO mice to developing penile abnormalities provides unequivocal evidence of an obligatory role for ERα in mediating the harmful effects of neonatal DES exposure in the developing penis.

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