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Equine estrogens induce apolipoprotein E and glial fibrillary acidic protein in mixed glial cultures.
Abstract: Premarin, which contains several equine estrogens, as well as estradiol (E2) as a minor component, is widely used for replacement therapy of estrogen deficits, but little is known of its direct actions on brain cells. In mixed glial cultures, apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) are induced by estrogens. GFAP induction showed an inverted-U shape E2 dose response, with a maximum induction at 1 pM, whereas apoE mRNA induction was greatest at 100 pM. GFAP and ApoE mRNAs were induced by equine estrogens in the following order: E2=equilin>estrone>17 alpha-dihydroequilenin. However, the induction of apoE secretion by 17 alpha-dihydroequilenin was as effective as by the other estrogens. The greater response of apoE secretion than GFAP mRNA induction to 17 alpha-dihydroequilenin might be therapeutically important because of the glial scarring during brain lesions, in which GFAP induction has a major role in inhibiting neurite outgrowth, whereas apoE secretion supports neurite outgrowth.
Publication Date: 2002-04-18 PubMed ID: 11959417DOI: 10.1016/s0304-3940(02)00146-5Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research focuses on understanding the effects of equine estrogens on brain cells by analyzing the induction of apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) in mixed glial cultures. The findings suggest that the equine estrogen, 17 alpha-dihydroequilenin, might have potential therapeutic value in situations of brain lesions, primarily due to its higher response in promoting apoE secretion over inducing GFAP.
Introduction and Context
- The study revolves around the evaluation of Premarin, a therapeutic drug composed mainly of equine estrogens and a minor component of estradiol (E2). It’s widely used to treat estrogen deficits in therapeutic contexts.
- The study intends to explore the direct effects of these equine estrogens on brain cells, which are not well established.
- The specific proteins focused on in this study – apolipoprotein E (apoE) and glial fibrillary acidic protein (GFAP) – are inducible by estrogens in glial cell cultures.
Experimental Findings
- The study discovered an “inverted-U” shape E2 dose response for GFAP induction, with maximum induction at concentrations of 1 pM.
- ApoE mRNA had a stronger induction at 100 pM, indicating a higher sensitivity to estrogen levels.
- Different equine estrogens resulted in differential mRNA induction rates for GFAP and ApoE. The induction order was E2 = equilin > estrone > 17 alpha-dihydroequilenin.
Significance and Therapeutic Implications
- The study noted that although 17 alpha-dihydroequilenin was the least effective at mRNA induction, it was equivalent to other estrogens in inducing the secretion of apoE.
- This differential in response might have therapeutic value because, in brain lesions, GFAP induction leads to glial scarring that inhibits neurite outgrowth. In contrast, apoE secretion is beneficial as it encourages neurite outgrowth.
- Therefore, 17 alpha-dihydroequilenin, given its ability to effectively induce apoE secretion while less effectively inducing GFAP, could potentially be beneficial in managing brain lesions and promoting neuronal regeneration.
Cite This Article
APA
Rozovsky I, Hoving S, Anderson CP, O'Callaghan J, Finch CE.
(2002).
Equine estrogens induce apolipoprotein E and glial fibrillary acidic protein in mixed glial cultures.
Neurosci Lett, 323(3), 191-194.
https://doi.org/10.1016/s0304-3940(02)00146-5 Publication
Researcher Affiliations
- Neurogerontology Division, Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, 3715 McClintoch Avenue, Los Angeles, CA 90089-0191, USA. rozovsky@molbio.usc.edu
MeSH Terms
- Animals
- Apolipoproteins E / genetics
- Astrocytes / cytology
- Astrocytes / drug effects
- Astrocytes / metabolism
- Brain / cytology
- Brain / drug effects
- Brain / metabolism
- Brain Injuries / drug therapy
- Brain Injuries / metabolism
- Brain Injuries / physiopathology
- Cells, Cultured
- Coculture Techniques
- Dose-Response Relationship, Drug
- Equilin / analogs & derivatives
- Equilin / pharmacology
- Estradiol / pharmacology
- Estrogens / metabolism
- Estrogens / pharmacology
- Estrogens, Conjugated (USP) / pharmacology
- Estrogens, Conjugated (USP) / therapeutic use
- Estrone / pharmacology
- Glial Fibrillary Acidic Protein / genetics
- Gliosis / drug therapy
- Gliosis / physiopathology
- Gliosis / prevention & control
- Horses
- Nerve Regeneration / drug effects
- Nerve Regeneration / physiology
- Neuronal Plasticity / drug effects
- Neuronal Plasticity / physiology
- Neuroprotective Agents / metabolism
- Neuroprotective Agents / pharmacology
- RNA, Messenger / drug effects
- RNA, Messenger / metabolism
- Rats
- Up-Regulation / drug effects
- Up-Regulation / physiology
Grant Funding
- AG-09793 / NIA NIH HHS
- AG-14751 / NIA NIH HHS
Citations
This article has been cited 16 times.- Valencia-Olvera AC, Maldonado Weng J, Christensen A, LaDu MJ, Pike CJ. Role of estrogen in women's Alzheimer's disease risk as modified by APOE. J Neuroendocrinol 2023 Feb;35(2):e13209.
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