Estrogen receptor-alpha splice variants in the human brain

Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology
Tatjana A Ishunina, D F Swaab

Abstract

In the present review we discuss recent findings showing that, in addition to the canonical estrogen receptor-alpha (ERalpha), the level of various ERalpha splice variants is changed in the human brain in aging and Alzheimer's disease (AD) at both the mRNA and protein level and that they should be considered for the understanding of estrogen effects on the brain and estrogen therapy pitfalls. Indeed, the expression pattern of certain splice forms is brain area-specific. Thus, the major isoform found in the mamillary body (MB) appeared to be del.7 (deletion of exon 7), while in the hippocampus del.4 (exon 4 omitted) was expressed at the highest level. Furthermore, while transcripts missing exons 7 and 2 declined with aging in the MB of patients >60 years old, no age-related alterations were determined for a number of splice variants in the hippocampus. A novel MB1 isoform with a 168-bp deletion within the transactivation function 1 of ERalpha turned out to accumulate in the histaminergic tuberomamillary nucleus of postmenopausal women. Finally, the level of alternatively spliced ERalpha may also change in AD in a brain area-specific manner and so affect the sensitivity to estrogen therapy.

References

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Citations

Mar 25, 2010·Neuroendocrinology·Paul MicevychJohn Kuo
Sep 24, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Reymundo Dominguez, Paul Micevych
Aug 22, 2014·The Journal of Endocrinology·Claire V HutchinsonColin Davidson
Jun 22, 2016·Molecular Neurobiology·Yu-Jie LaiGuo-Jun Chen
Jan 4, 2013·Reproduction in Domestic Animals = Zuchthygiene·J SchoenK Jewgenow
Oct 1, 2013·Pharmacological Reviews·Deepak P SrivastavaPeter Penzes
Feb 5, 2010·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Pascale Fehlbaum-BeurdeleyLaurent Bracco

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