Cross talk between peptide growth factor and estrogen receptor signaling systems.

Ignar-Trowbridge, Diane M.; Pimentel, M; Teng, Christina T.; Korach, Kenneth S.; McLachlan, John A.

doi:10.1289/ehp.95103s735

Cited by 83 publications

(40 citation statements)

References 37 publications

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“…Of particular interest is the poor responsiveness of ER-positive Ishikawa cells to E2. This cell line is well known to express ER but at low levels (21,22). The overexpression of ER␣ in this cell line was able to induce CYP1B1 transcriptional activity in the presence of E2.…”

Section: Discussionmentioning

confidence: 91%

Human CYP1B1 Is Regulated by Estradiol via Estrogen Receptor

Tsuchiya¹,

Nakajima²,

et al. 2004

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Human cytochrome P450 (CYP) 1B1 is a key enzyme in the metabolism of 17␤-estradiol (E2). CYP1B1 is mainly expressed in endocrine-regulated tissues, such as mammary, uterus, and ovary. Because many CYP enzymes are likely to be induced by the substrates themselves, we examined whether the human CYP1B1 expression is regulated by E2 in the present study. Real-time reverse transcription-PCR analysis revealed that treatment with 10 nM E2 for 12 h induced CYP1B1 mRNA expression in estrogen receptor (ER)-positive MCF-7 cells. Luciferase reporter assays using MCF-7 cells showed a significant transactivation up to 7-fold by E2 with a reporter plasmid containing a region from ؊152 to ؉25 of the human CYP1B1 gene. A computer-assisted homology search indicated a putative estrogen response element (ERE) between ؊63 and ؊49 in the CYP1B1 promoter region. Specific binding of ER␣ to the putative ERE was demonstrated by chromatin immunoprecipitation assays and gel shift analyses. With reporter plasmids containing the wild or mutated putative ERE on the CYP1B1 gene and the wild or mutated ER␣ expression vectors, luciferase assays using Ishikawa cells demonstrated that the putative ERE and ER␣ are essential for the transactivation by E2. Because endometrial tissue is highly regulated by estrogens, the expression pattern of CYP1B1 protein in human endometrial specimens was examined by immunohistochemistry. The staining of CYP1B1 was stronger in glandular epithelial cells during a proliferative phase than those during a secretory phase, consistent with the pattern of estrogen secretion. These findings clearly indicated that the human CYP1B1 is regulated by estrogen via ER␣. Because 4-hydroxylation of estrogen by CYP1B1 leads to decrease of the estrogenic activity but the produced metabolite is toxicologically active, our findings suggest a clinical significance in the estrogenregulated CYP1B1 expression for the homeostasis of estrogens as well as estrogen-dependent carcinogenesis.

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Section: Discussionmentioning

confidence: 91%

Human CYP1B1 Is Regulated by Estradiol via Estrogen Receptor

Tsuchiya¹,

Nakajima²,

et al. 2004

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“…These researchers showed that a protein kinase-C activator acted synergistically with 173-estradiol to induce ERE-dependent transcription. They also showed that epidermal growth factor, which produces estrogenlike effects in the mouse reproductive tract, increases levels of nuclear ER (12). These researchers note that the potential health effects associated with exposure to exogenous estrogens may also be observed following exposure to chemicals that could activate peptide growth factor signaling systems.…”

Section: Er Dynamics: Nuclear Accumulation and Impact Of Pharmacokinementioning

confidence: 94%

“…Plasma membraneresident forms of ER have been proposed to explain observations of cellular responses to estrogen that occur within minutes and so cannot be explained through gene transcription (65). In addition, other researchers have shown that chemicals-that activate peptide growth factor signaling systems, such as protein kinase-C activators, can also induce ERE-dependent transcription (12). These researchers showed that a protein kinase-C activator acted synergistically with 173-estradiol to induce ERE-dependent transcription.…”

Section: Er Dynamics: Nuclear Accumulation and Impact Of Pharmacokinementioning

confidence: 99%

“…Estrogenic compounds have also OP, 4-tert-octylphenol; PCBs, polychlorinated biphenyls; SDN-POA, sexually dimorphic nucleus in the preoptic area of the hypothalamus; SHBG, sex hormone-binding globulin; 2,3,7,8-TCDD, 2,3,7,8-tetrachlorodibenzo-pdioxin; TEF, toxic equivalence factor. been reported to have other effects, such as involvement in other cell signaling pathways that may stimulate receptor-mediated estrogen action, e.g., protein kinase C (2,12,13), inhibition of microtubule polymerization (14), or inhibition of gap-junctional intercellular communitation (GJIC) (15).…”

Section: Introductionmentioning

confidence: 99%

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Predicting health effects of exposures to compounds with estrogenic activity: methodological issues.

Rudel

1997

Environ Health Perspect

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Many substances are active in in vitro tests for estrogenic activity, but data from multigenerational and other toxicity studies are not available for many of those substances. Controversy has arisen, therefore, concerning the likelihood of adverse health effects. Based on a toxic equivalence factor risk assessment approach, some researchers have concluded that exposure to environmental estrogens is not associated with estrogen receptor (ER)-mediated health effects. Their rationale cites the low potency of these compounds in in vitro assays relative to estradiol, and the widespread exposure to pharmaceutical, endogenous, and dietary estrogens. This reasoning relies on two assumptions: that the relative estrogenic potency in in vitro assays is predictive of the relative potency for the most sensitive in vivo estrogenic effect; and that all estrogens act via the same mechanism to produce the most sensitive in vivo estrogenic effect. Experimental data reviewed here suggest that these assumptions may be inappropriate because diversity in both mechanism and effect exists for estrogenic compounds. Examples include variations in ER-ligand binding to estrogen response elements, time course of nuclear ER accumulation, patterns of gene activation, and other mechanistic characteristics that are not reflected in many in vitro assays, but may have significance for ER-mediated in vivo effects. In light of these data, this report identifies emerging methodological issues in risk assessment for estrogenic compounds: the need to address differences in in vivo end points of concern and the associated mechanisms; pharmacokinetics; the crucial role of timing and duration of exposure; interactions; and non-ER-mediated activities of estrogenic compounds. Environ Health Perspect 1 05(Suppl 3): 655-663 (1997)

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“…Dependence, the third major category of potential interactions, to some extent overlaps with induction -for example, induction of growth factor synthesis may be required for full expression of steroid effects on target tissues [1,2]. However, it also includes examples of situations in which components of steroid response pathways may be required for full expression of growth factor effects.…”

Section: Introductionmentioning

confidence: 99%

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

Scharfman

MacLusky

2006

Frontiers in Neuroendocrinology

270

202

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In the CNS, there are widespread and diverse interactions between growth factors and estrogen. Here we examine the interactions of estrogen and brain-derived neurotrophic factor (BDNF), two molecules that have historically been studied separately, despite the fact that they seem to share common targets, effects, and mechanisms of action. The demonstration of an estrogen-sensitive response element on the BDNF gene provided an impetus to explore a direct relationship between estrogen and BDNF, and predicted that the effects of estrogen, at least in part, might be due to the induction of BDNF. This hypothesis is discussed with respect to the hippocampus, where substantial evidence has accumulated in favor of it, but alternate hypotheses are also raised. It is suggested that some of the interactions between estrogen and BDNF, as well as the controversies and implications associated with their respective actions, may be best appreciated in light of the ability of BDNF to induce neuropeptide Y (NPY) synthesis in hippocampal neurons. Taken together, this tri-molecular cascade, estrogen-BDNF-NPY, may be important in understanding the hormonal regulation of hippocampal function. It may also be relevant to other regions of the CNS where estrogen is known to exert profound effects, such as amygdala and hypothalamus; and may provide greater insight into neurological disorders and psychiatric illness, including Alzheimer's disease, depression and epilepsy.

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Cross talk between peptide growth factor and estrogen receptor signaling systems.

Cited by 83 publications

References 37 publications

Human CYP1B1 Is Regulated by Estradiol via Estrogen Receptor

Human CYP1B1 Is Regulated by Estradiol via Estrogen Receptor

Predicting health effects of exposures to compounds with estrogenic activity: methodological issues.

Estrogen and brain-derived neurotrophic factor (BDNF) in hippocampus: Complexity of steroid hormone-growth factor interactions in the adult CNS

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