Estradiol-Induced Estrogen Receptor-α Trafficking

Bondar, G.; Kuo, John S.; Hamid, Naheed; Micevych, Paul E.

doi:10.1523/jneurosci.2107-09.2009

Cited by 118 publications

(184 citation statements)

References 58 publications

Supporting

Mentioning

165

Contrasting

Order By: Relevance

“…2) [86,87,120]. These studies demonstrated surface biotinylated ERα-immunoreactive proteins, indicating that a portion of the ERα is exposed on the cell surface and implying that ERα is a membrane protein.…”

Section: Astrocytes and Reproduction In Femalesmentioning

confidence: 99%

“…In addition to the classic ERα and ERβ, several other estrogen-binding proteins have been proposed including ER-X, GPR30 and a STX-activated protein [reviewed in [84]]. To date, we have concentrated on ERα and ERβ because: (1) transfection of ER-negative cells with ERα or ERβ mRNA produce cognate proteins in the membrane fraction that are functional [85]; (2) Western blots with ER-specific antibodies demonstrate both full-length and splice variants of the ER in the membrane fraction of neurons and astrocytes [22,86,87]; (3) the binding affinity (K D ) for the membrane ER and nuclear ER is similar, but there are fewer ERs on the membrane (B MAX ) [88], and (4) ERα and ERβ proteins are trafficked and attached to the membrane through palmitoylation and in association with calveolin proteins [89,90,91,92,93]. …”

Section: Astrocytes and Reproduction In Femalesmentioning

confidence: 99%

See 1 more Smart Citation

Estrogen Actions on Neuroendocrine Glia

2010

View full text Add to dashboard Cite

Astrocytes are the most abundant cells in the central nervous system (CNS). It appears that astrocytes are as diverse as neurons, having different phenotypes in various regions throughout the brain and participating in intercellular communication that involves signaling to neurons. It is not surprising then that astrocytes in the hypothalamus have an active role in the CNS regulation of reproduction. In addition to the traditional mechanism involving ensheathment of neurons and processes, astrocytes may have a critical role in regulating estrogen-positive feedback. Work in our laboratory has focused on the relationship between circulating estradiol and progesterone synthesized de novo in the brain. We have demonstrated that circulating estradiol stimulates the synthesis of progesterone in adult hypothalamic astrocytes, and this neuroprogesterone is critical for initiating the LH surge. Estradiol cell signaling is initiated at the cell membrane and involves the transactivation of metabotropic glutamate receptor type 1a (mGluR1a) leading to the release of intracellular stores of calcium. We used surface biotinylation to demonstrate that estrogen receptor-α (ERα) is present in the cell membrane and has an extracellular portion. Like other membrane receptors, ERα is inserted into the membrane and removed via internalization after agonist stimulation. This trafficking is directly regulated by estradiol, which rapidly and transiently increases the levels of membrane ERα, and upon activation, increases internalization that finally leads to ERα degradation. This autoregulation temporally limits membrane-initiated estradiol cell signaling. Thus, neuroprogesterone, the necessary signal for the LH surge, is released when circulating levels of estradiol peak on proestrus and activate progesterone receptors whose expression has been induced by the gradual rise of estradiol during follicular development.

show abstract

Section: Astrocytes and Reproduction In Femalesmentioning

confidence: 99%

Section: Astrocytes and Reproduction In Femalesmentioning

confidence: 99%

Estrogen Actions on Neuroendocrine Glia

2010

View full text Add to dashboard Cite

show abstract

“…Data such as these have led to a general acceptance that a membrane-associated ER facilitates the rapid nonclassical effects of E 2 (e.g., Micevych and Dominguez 2009) and have prompted some investigators to suggest that BSA-E 2 binds to ERa and ERb localized within the membrane (Meitzen and Mermelstein 2011). Although one provocative report indicates that ERa in the hypothalamus has an extracellular domain and can be internalized by E 2 and mGluR1a ligands (Bondar et al 2009), it is not yet widely accepted that ERa is an integral membrane protein.…”

Section: Estrogen Receptor Localization and Mechanism Of Action Era Amentioning

confidence: 99%

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

et al. 2015

View full text Add to dashboard Cite

Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17b-estradiol (E 2 ), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E 2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E 2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E 2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs.Hormones have long been known to play key roles in regulating learning and memory. Many hormones, including epinephrine, glucocorticoids, and insulin influence learning and memory via inverted U-shaped dose-response relationships in which memory is enhanced by moderate, but not low or high, hormone levels (Roozendaal 2000;Korol and Gold 2007;McNay and Recknagel 2011). Research from the past two decades has demonstrated that sex steroid hormones, particularly the potent estrogen 17b-estradiol (E 2 ), also regulate learning and memory in male and female rodents via an inverted U-shaped dose-response function that is influenced by estrogen receptor expression (Packard and Teather 1997a;Packard 1998;Foster 2012). Yet E 2 has not gained widespread acceptance as a hormonal modulator of memory in both females and males, perhaps because the majority of this research has been conducted in female rodents. Moreover, the common view of E 2 as a "female" hormone may contribute to the misperception that E 2 is not relevant for cognitive function in males. However, considerable evidence supports a vital role for E 2 in mediating neural function and behavior in male rodents. Therefore, it is important for investigators working with males to understand the ways in which E 2 and other sex steroid hormones (e.g., androgens, progestins, and other estrogens) may influence their brain regions and behaviors of interest.Another reason for investigators to be cognizant of sex steroid hormone-induced regulation of learning and memory is that males and females may respond differently to various treatments and environmental factors. A classic example is that of acute stress, which enhances classical conditioning and increases apical CA1 dendritic spine density in male rats, but impairs classical conditioning and decreases CA1 spine density in female rats (Wood and Shors 1998;Shors et al. 2001). Therefore, investigators hoping to comply with National Institutes of Health policies that encourage the inclusion of females in biomedical research must be aware that adding females to a study is not as simple as adding another group. In some ways, females are fundamentally different from males, the most obvious of which is the presence of reproductive...

show abstract

“…MCF-7 cells were cultured at a density of 3x10 5 cells/well in 6-well plates and then were treated with E2, BPA, MXC or EtOH. MCF-7 cells were cultured at a density of 3x10 5 cells/well in 6-well plates, treated with E2, BPA, MXC and EtOH; and co-treated with ICI 182,780, PPT or DPN. Total-RNA was extracted at various time points (0, 6 and 24 h) using TRIzol reagent (Invitrogen Life Technologies, Carlsbad, CA, USA) according to the manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Most natural and synthetic EDCs tend to have estrogenic activities and structures similar to that of estrogen such as 17β-estradiol (E2); thus, they induce estrogen-mediated responses by binding to estrogen receptors (ERs) (4). ERs are members of the nuclear receptor family and play a key role as transcription factors (TFs) in gene expression (5). Estrogen is known to be essential for the development of reproductive organs, bone, and the cardiovascular system (6,7).…”

Section: Introductionmentioning

confidence: 99%

Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway

Choi

2012

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Various endocrine disrupting chemicals (EDCs) are exogenous compounds found in the environment and have the potential to interfere with the endocrine system and hormonal regulation. Among EDCs, bisphenol A (BPA) and 1,1,1-trichloro-2,2-bis(4-methoxyphenol)-ethane [methoxychlor (MXC)] have estrogenic activity resulting in a variety of dysfunctions in the E2-mediated response by binding to estrogen receptors (ERs), causing human health problems such as abnormal reproduction and carcinogenesis. In this study, we investigated the effects of BPA and MXC on cell proliferation facilitated by ER signaling in human breast cancer cells. MCF-7 cells are known to be ERα-positive and to be a highly E2-responsive cancer cell line; these cells are, therefore, a useful in vitro model for detecting estrogenic activity in response to EDCs. We evaluated cancer cell proliferation following BPA and MXC treatment using an MTT assay. We analyzed alterations in the expression of genes associated with the cell cycle in MCF-7 cells by semi-quantitative reverse-transcription PCR following treatment with BPA or MXC compared to EtOH. To determine whether BPA and MXC stimulate cancer cell growth though ER signaling, we co-treated the cells with agonists (propyl pyrazoletriol, PPT; and diarylpropionitrile, DPN) or an antagonist (ICI 182,780) of ER signaling and reduced ERα gene expression via siRNA in MCF-7 cells before treatment with EDCs. These studies confirmed the carcinogenicity of EDCs in vitro. As a result, BPA and MXC induced the cancer cell proliferation by the upregulation of genes that promote the cell cycle and the downregulation of anti-proliferative genes, especially ones affecting the G1/S transition via ERα signaling. These collective results confirm the carcinogenicity of these EDCs in vitro. Further studies are required to determine whether EDCs promote carcinogenesis in vivo.

show abstract

Estradiol-Induced Estrogen Receptor-α Trafficking

Cited by 118 publications

References 58 publications

Estrogen Actions on Neuroendocrine Glia

Estrogen Actions on Neuroendocrine Glia

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

Treatment with bisphenol A and methoxychlor results in the growth of human breast cancer cells and alteration of the expression of cell cycle-related genes, cyclin D1 and p21, via an estrogen receptor-dependent signaling pathway

Contact Info

Product

Resources

About