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 types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apolipoproteins E / genetics*
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Astrocytes / cytology
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Astrocytes / drug effects*
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Astrocytes / metabolism
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Brain / cytology
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Brain / drug effects*
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Brain / metabolism
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Brain Injuries / drug therapy
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Brain Injuries / metabolism
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Brain Injuries / physiopathology
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Cells, Cultured
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Coculture Techniques
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Dose-Response Relationship, Drug
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Equilin / analogs & derivatives*
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Equilin / pharmacology
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Estradiol / pharmacology
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Estrogens / metabolism
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Estrogens / pharmacology*
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Estrogens, Conjugated (USP) / pharmacology
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Estrogens, Conjugated (USP) / therapeutic use
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Estrone / pharmacology
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Glial Fibrillary Acidic Protein / genetics*
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Gliosis / drug therapy
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Gliosis / physiopathology
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Gliosis / prevention & control
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Horses
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Nerve Regeneration / drug effects
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Nerve Regeneration / physiology
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Neuroprotective Agents / metabolism
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Neuroprotective Agents / pharmacology*
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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Rats
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Up-Regulation / drug effects*
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Up-Regulation / physiology
Substances
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Apolipoproteins E
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Estrogens
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Estrogens, Conjugated (USP)
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Glial Fibrillary Acidic Protein
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Neuroprotective Agents
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RNA, Messenger
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Equilin
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Estrone
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Estradiol
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dihydroequilin