Are There Biological Bases for a Beneficial Effect of Estrogens in Neural Diseases?

Maggi, Adriana; Ciana, Paolo; Brusadelli, Alessia; Belcredito, Silvia; Bonincontro, Cinzia; Vegeto, Elisabetta

doi:10.1006/hbeh.2001.1694

Cited by 2 publications

(2 citation statements)

References 68 publications

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“…Because of the known effects of estrogens on proliferation and differentiation of reproductive tissues, these receptors may be good candidates as nuclear effectors completing the program originated by membrane receptor. Several studies, showing that estrogen has a key role in the differentiation of neurons localized in selected brain regions, support this view (6). Previous work from our laboratory demonstrated the existence of a crosscoupling between ER␣ and insulin growth factor in neural cells (7,8) subsequently confirmed by several other groups (9 -11).…”

supporting

confidence: 55%

Estrogen Receptor α, a Molecular Switch Converting Transforming Growth Factor-α-mediated Proliferation into Differentiation in Neuroblastoma Cells

Ciana¹,

Ghisletti²,

Mussi³

et al. 2003

Journal of Biological Chemistry

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Transforming growth factor-␣ (TGF-␣) is known to promote both proliferation and differentiation of neural cell progenitors. Using the human neuroblastoma cell line SK-N-BE that is induced to proliferate by TGF-␣, we demonstrated that the expression of a single transcription factor, the estrogen receptor-␣ (ER␣), can reroute the TGF-␣ mitogenic signaling toward a path leading to differentiation. With selected mutations in ER␣ and signal transducer and activator of transcription 3 (Stat3), we demonstrated that the blockade of TGF-␣ mitotic potential was not dependent on ER␣ DNA binding activity but required a transcriptionally active Stat3. In neuroblastoma cells, 17␤-estradiol treatment induced a transient increase in the transcription of estrogen-responsive element-containing promoters including those regulating TGF-␣ and prothymosin ␣ synthesis. Based on the data presented, we hypothesized that in the presence of prothymosin ␣, ER␣ activates its direct target genes and increases cell proliferation, whereas in the presence of high levels of TGF-␣, ER␣ preferentially interacts with Stat3 and causes cell differentiation. Our results reveal a novel form of "end-product" regulation of an intracellular receptor that occurs through recruitment of membrane receptors and their signaling effector system. Cross-coupling between membrane and intracellular receptors has been described by several laboratories. This study proves the relevance of these interactions in cellular responses to growth factors.

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supporting

confidence: 55%

Estrogen Receptor α, a Molecular Switch Converting Transforming Growth Factor-α-mediated Proliferation into Differentiation in Neuroblastoma Cells

Ciana¹,

Ghisletti²,

Mussi³

et al. 2003

Journal of Biological Chemistry

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“…They become activated in response to injury and initiate a pattern of events marked by proliferation, migration to the site of injury, and changes in both morphology and cell surface markers (346). Recent work establishes that microglia play a critical role in response to injury (347,348). Both in vivo and in vitro studies have shown that E 2 suppresses microglial activation and that this response is regulated by ERs (117,119,125,349).…”

Section: Mechanisms Of Estrogen Action In the Central Nervous Systemmentioning

confidence: 99%

Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies

et al. 2006

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Recent publications describing the results of the Women's Health Initiative (WHI) and other studies reporting the impact of hormone therapy on aging women have spurred reexamination of the broad use of estrogens and progestins during the postmenopausal years. Here, we review the complex pharmacology of these hormones, the diverse and sometimes opposite effects that result from the use of different estrogenic and progestinic compounds, given via different delivery routes in different concentrations and treatment sequence, and to women of different ages and health status. We examine our new and growing appreciation of the role of estrogens in the immune system and the inflammatory response, and we pose the concept that estrogen's interface with this system may be at the core of some of the effects on multiple physiological systems, such as the adipose/metabolic system, the cardiovascular system, and the central nervous system. We compare and contrast clinical and basic science studies as we focus on the actions of estrogens in these systems because the untoward effects of hormone therapy reported in the WHI were not expected. The broad interpretation and publicity of the results of the WHI have resulted in a general condemnation of all hormone replacement in postmenopausal women. In fact, careful review of the extensive literature suggests that data resulting from the WHI and other recent studies should be interpreted within the narrow context of the study design. We argue that these results should encourage us to perform new studies that take advantage of a dialogue between basic scientists and clinician scientists to ensure appropriate design, incorporation of current knowledge, and proper interpretation of results. Only then will we have a better understanding of what hormonal compounds should be used in which populations of women and at what stages of menopausal/postmenopausal life.

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Are There Biological Bases for a Beneficial Effect of Estrogens in Neural Diseases?

Cited by 2 publications

References 68 publications

Estrogen Receptor α, a Molecular Switch Converting Transforming Growth Factor-α-mediated Proliferation into Differentiation in Neuroblastoma Cells

Estrogen Receptor α, a Molecular Switch Converting Transforming Growth Factor-α-mediated Proliferation into Differentiation in Neuroblastoma Cells

Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies

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