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
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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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 14 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.
- Marongiu R. Accelerated Ovarian Failure as a Unique Model to Study Peri-Menopause Influence on Alzheimer's Disease.. Front Aging Neurosci 2019;11:242.
- Hohman TJ, Dumitrescu L, Barnes LL, Thambisetty M, Beecham G, Kunkle B, Gifford KA, Bush WS, Chibnik LB, Mukherjee S, De Jager PL, Kukull W, Crane PK, Resnick SM, Keene CD, Montine TJ, Schellenberg GD, Haines JL, Zetterberg H, Blennow K, Larson EB, Johnson SC, Albert M, Bennett DA, Schneider JA, Jefferson AL. Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau.. JAMA Neurol 2018 Aug 1;75(8):989-998.
- Ma Y, Guo H, Zhang L, Tao L, Yin A, Liu Z, Li Y, Dong H, Xiong L, Hou W. Estrogen replacement therapy-induced neuroprotection against brain ischemia-reperfusion injury involves the activation of astrocytes via estrogen receptor β.. Sci Rep 2016 Feb 19;6:21467.
- Fan J, Shimizu Y, Chan J, Wilkinson A, Ito A, Tontonoz P, Dullaghan E, Galea LA, Pfeifer T, Wellington CL. Hormonal modulators of glial ABCA1 and apoE levels.. J Lipid Res 2013 Nov;54(11):3139-50.
- Espeland MA, Brunner RL, Hogan PE, Rapp SR, Coker LH, Legault C, Granek I, Resnick SM. Long-term effects of conjugated equine estrogen therapies on domain-specific cognitive function: results from the Women's Health Initiative study of cognitive aging extension.. J Am Geriatr Soc 2010 Jul;58(7):1263-71.
- Carroll JC, Rosario ER, Villamagna A, Pike CJ. Continuous and cyclic progesterone differentially interact with estradiol in the regulation of Alzheimer-like pathology in female 3xTransgenic-Alzheimer's disease mice.. Endocrinology 2010 Jun;151(6):2713-22.
- Zhang HL, Wu J, Zhu J. The role of apolipoprotein E in Guillain-Barré syndrome and experimental autoimmune neuritis.. J Biomed Biotechnol 2010;2010:357412.
- Wharton W, Gleason CE, Lorenze KR, Markgraf TS, Ries ML, Carlsson CM, Asthana S. Potential role of estrogen in the pathobiology and prevention of Alzheimer's disease.. Am J Transl Res 2009 Jan 20;1(2):131-47.
- Espeland MA, Tindle HA, Bushnell CA, Jaramillo SA, Kuller LH, Margolis KL, Mysiw WJ, Maldjian JA, Melhem ER, Resnick SM. Brain volumes, cognitive impairment, and conjugated equine estrogens.. J Gerontol A Biol Sci Med Sci 2009 Dec;64(12):1243-50.
- Brinton RD, Thompson RF, Foy MR, Baudry M, Wang J, Finch CE, Morgan TE, Pike CJ, Mack WJ, Stanczyk FZ, Nilsen J. Progesterone receptors: form and function in brain.. Front Neuroendocrinol 2008 May;29(2):313-39.
- Brown CM, Choi E, Xu Q, Vitek MP, Colton CA. The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol.. Neurobiol Aging 2008 Dec;29(12):1783-94.
- Wang JM, Irwin RW, Brinton RD. Activation of estrogen receptor alpha increases and estrogen receptor beta decreases apolipoprotein E expression in hippocampus in vitro and in vivo.. Proc Natl Acad Sci U S A 2006 Nov 7;103(45):16983-8.
- Nathoo N, Chetty R, van Dellen JR, Barnett GH. Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E.. Mol Pathol 2003 Jun;56(3):132-6.
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