scholarly journals Hypoxia Limits the Growth of Bovine Follicles in Vitro by Inhibiting Estrogen Receptor α

Animals ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 551 ◽  
Author(s):  
Ma ◽  
Wang ◽  
Gao ◽  
Liu ◽  
Zheng ◽  
...  

Female animals living in the Qinghai-Tibet Plateau have lower ovulation rates because of the hypoxic environment, however, the mechanism of hypoxia on animal follicles is unclear. In this study, the effects of hypoxia on bovine follicles were investigated using an in vitro follicular culture system. The results show that there was a significant decrease in follicular diameter from day 3 to day 6 in both hypoxia and hypoxia with estrogen (E2) and fulvestrant (ICI 182780) (hypoxia + E2 + ICI) groups, when compared with a normoxia group (p < 0.05). We also observed significant downregulation of ERα and FSHR, while upregulation of LHCGR expression in the hypoxia group and hypoxia + E2 + ICI groups compared to the normoxia group (p < 0.05). The expression of IGF1 gene was significantly downregulated in hypoxia + E2 + ICI group when compared to the hypoxia + E2 group (p < 0.05). The expression of HIF1A, ADAMTS1, VEGFA, and EDN2 were upregulated in both hypoxia and hypoxia + E2 + ICI groups in comparison to normoxia group (p < 0.05). Under hypoxic conditions, the addition of E2 resulted in a decrease of HIF1A protein but an increase of ERα protein in cultured bovine follicles (p < 0.05). In summary, hypoxia limits the growth of bovine follicle cultured in vitro through inhibition of ERα.

2018 ◽  
Vol 39 (3) ◽  
Author(s):  
Kyle T. Helzer ◽  
Mary Szatkowski Ozers ◽  
Mark B. Meyer ◽  
Nancy A. Benkusky ◽  
Natalia Solodin ◽  
...  

ABSTRACT Posttranslational modifications are key regulators of protein function, providing cues that can alter protein interactions and cellular location. Phosphorylation of estrogen receptor α (ER) at serine 118 (pS118-ER) occurs in response to multiple stimuli and is involved in modulating ER-dependent gene transcription. While the cistrome of ER is well established, surprisingly little is understood about how phosphorylation impacts ER-DNA binding activity. To define the pS118-ER cistrome, chromatin immunoprecipitation sequencing was performed on pS118-ER and ER in MCF-7 cells treated with estrogen. pS118-ER occupied a subset of ER binding sites which were associated with an active enhancer mark, acetylated H3K27. Unlike ER, pS118-ER sites were enriched in GRHL2 DNA binding motifs, and estrogen treatment increased GRHL2 recruitment to sites occupied by pS118-ER. Additionally, pS118-ER occupancy sites showed greater enrichment of full-length estrogen response elements relative to ER sites. In an in vitro DNA binding array of genomic binding sites, pS118-ER was more commonly associated with direct DNA binding events than indirect binding events. These results indicate that phosphorylation of ER at serine 118 promotes direct DNA binding at active enhancers and is a distinguishing mark for associated transcription factor complexes on chromatin.


Endocrinology ◽  
2004 ◽  
Vol 145 (1) ◽  
pp. 113-125 ◽  
Author(s):  
Dong-bao Chen ◽  
Ian M. Bird ◽  
Jing Zheng ◽  
Ronald R. Magness

Abstract Rapid uterine vasodilatation after estrogen administration is believed to be mediated by endothelial production of nitric oxide (NO) via endothelial NO synthase (eNOS). However, the mechanism(s) by which estrogen activates eNOS in uterine artery endothelial cells (UAEC) is unknown. In this study, we observed that estradiol-17β (E2) and E2-BSA rapidly (&lt;2 min) increased total NOx production in UAEC in vitro. This was associated with rapid eNOS phosphorylation and activation but was unaltered by pretreatment with actinomycin-D. estrogen receptor-α protein was detectable in isolated plasma membrane proteins by immunoblotting, and E2-BSA-fluorescein isothiocyanate binding was evident on the plasma membrane of UAEC. E2 did not mobilize intracellular Ca2+, but E2 and ionomycin in combination induced greater eNOS phosphorylation than either E2 or ionomycin alone. E2 did not stimulate rapid Akt phosphorylation. E2 stimulated rapid ERK2/1 activation in a time- and dose-dependent manner, with maximal responses observed at 5–10 min with E2 (10 nm to 1 μm) treatment. Acute activation of eNOS and NOx production by E2 could be inhibited by PD98059 but not by LY294002. When E2-BSA was applied, similar responses in NOx production, eNOS, and ERK2/1 activation to those of E2 were achieved. In addition, E2 and E2-BSA-induced ERK2/1 activation and ICI 182,780 could inhibit NOx production by E2. Thus, acute activation of eNOS to produce NO in UAEC by estrogen is at least partially through an ERK pathway, possibly via estrogen receptor localized on the plasma membrane. This pathway may provide a novel mechanism for NO-mediated rapid uterine vasodilatation by estrogen.


Author(s):  
Qiguo Tang ◽  
Qinqin Xu ◽  
Cui Ding ◽  
Hao Zhang ◽  
Yao Ling ◽  
...  

The Tibetan chickens (Gallus gallus; TBC) are an indigenous breed distributed in Qinghai-Tibet Plateau that are well adapted to a hypoxic environment. The energy metabolism of embryo brains in TBCs under hypoxia has been little reported. This study investigated changes in energy metabolism of TBCs brain during embryo development under hypoxia. We found TBCs exhibited a change of glycolysis and TCA cycle during embryo development under hypoxia. HIF-1 potentially involved this by directly inducing the overexpression of PDK1 and glycolytic genes, hexokinase(HK1) and lactate dehydrogenase A (LDHA) to increase glycolysis of TBCs to adapt hypoxia. Although these may not be unique to TBCs, as we had also found similar results in Dwarf Laying Chickens (DLCs), a lowland chicken breed, TBCs had stronger regulating ability. In summary, our study revealed HIF-1 induced energy metabolism change in TBCs brain via upregulating expressions of PDK1 and other HIF-1 target genes like HK1, LDHA to increase glycolysis for TBCs hypoxia adaptation during embryo development. It indicates the potential application of TBCs energy metabolism research for other animals living on the Qinghai-Tibet Plateau.


Author(s):  
Eldafira Eldafira ◽  
Abinawanto Abinawanto ◽  
Luthfiralda Sjahfirdi ◽  
Asmarinah Asmarinah ◽  
Purnomo Soeharso ◽  
...  

Endometriosis is a multifactorial disease in which genetic and environmental factors interact causing its pathogenesis. The aim of this study was to investigate the expression pattern of estrogen receptor α (ERα) and β (ERβ) in endometriosis patients compared to normal endometrioum (n=18) as a control by using Quantitative Real Time PCR method. Moreover, we also measured serum estradiol levels of endometriosis patients in the proliferation phase of the menstrual cycle using the enzyme-linked immunosorbent assay method. The mRNA expression of ERβ was significantly higher in the endometriosis group compared to control, and the result of t-test showed that were significantly different (P<0.05). Overexpression of ERβ in endometriosis was likely to have other significant important impacts in the pathology of endometriosis that allowed ERβ to stimulate prostaglandin production in endometriosis tissue and cells. Estradiol content did not correlate with the ERα expression, and it is weakly correlated with ERβ mRNA expression. Molecular docking analysis showed that ERα and ERβ have different binding interactions with synthetic antiestrogens, whereas the best inhibitor was Ral2 to ERα and Aco1 to ERβ. Thus, both inhibitors could be used as leads in further investigation of ERα, ERβ inhibitory activities in vitro and in vivo.


2004 ◽  
Vol 75 (6) ◽  
pp. 1166-1172 ◽  
Author(s):  
K. Chad Lambert ◽  
Edward M. Curran ◽  
Barbara M. Judy ◽  
Dennis B. Lubahn ◽  
D. Mark Estes

2019 ◽  
Vol 12 (6) ◽  
pp. 993-1008 ◽  
Author(s):  
Xixi Yao ◽  
Jianping Wu ◽  
Xuyin Gong

AbstractAimsGrasslands used for animal husbandry are chosen depending on the nutritive values of dominant herbage species. However, the influence of grazing in combination with precipitation and growing season on the nutritive values of dominant species has not been explicated.MethodsTo unveil the influence of the different grazing intensities on the nutritional values, an ecological study was formulated, namely fencing (G0), light grazing (G1), moderate grazing (G2) and high grazing (G3). This ambitious study was undertaken on the nutritive values of the four dominant species of herbage in an alpine meadow on the Qinghai-Tibet Plateau (QTP) during growing season (June–September) for two successive years, namely 2015 (rainy year) and 2016 (droughty year).Important FindingsWe found that (i) the nutritive value of Kobresia capillifolia, Polygonum viviparum and Caragana sinica was noticeably increased by grazing, but negligible effect on Potentilla fruticosa nutritive value was recorded. (ii) During the rainy year (2015), compared with G0, Polygonum viviparum and Potentilla fruticosa displayed 5.4 and 1.5% increases in the crude protein (CP) content and 8.5 and 2.4% increases in vitro true digestibility (IVTD), respectively, while the neutral detergent fibre (NDF) decreased by 13.5 and 0.9%, respectively. During the droughty year (2016), compared with G0, C. sinica and Potentilla fruticosa showed increases in the CP content by 4.3 and 1.3% and increases in the IVTD by 10.7 and 0.4%, respectively, during G3, while the NDF decreased by 6.0 and 1.0%, respectively. (iii) The nutritive values of all species were higher in the years when the rains were good. However, the nutritive values suffered heavily during drought conditions. Besides, the highest and lowest values of nutrition were detected in June and in September, respectively. The inter-seasonal and the inter-annual changes in the nutritional values of species were higher for K. capillifolia and Polygonum viviparum than for Potentilla fruticosa and C. sinica, suggesting that Potentilla fruticosa and C. sinica had higher water-use efficiency. (iv) Grazing clearly reduced the drought tolerance of three species and showed no effects on Potentilla fruticosa. (v) Grazing clearly increased the inter-month variation in the nutritional value of K. capillifolia and Polygonum viviparum but showed no effects on Potentilla fruticosa or C. sinica. Evidently, the grazing effects impacting the nutritional value of the dominant species of herbage exhibited conspicuous inter-annual and seasonal variations with species-specific influences and responses. Our findings are expected to have far-reaching implications enabling the authorities to arrive at strategic decisions and designing of relevant policies for the efficient management of the ecosystems ensuring the speed restoration of the QTP under severe grazing and extreme climatic circumstances.


2001 ◽  
Vol 183 (3) ◽  
pp. 223-227 ◽  
Author(s):  
Horst Claassen ◽  
Joachim Hassenpflug ◽  
Michael Schünke ◽  
Walter Sierralta ◽  
Hubert Thole ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document