Equine estrogens induce apolipoprotein E and glial fibrillary acidic protein in mixed glial cultures.
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.
Rozovsky
Irina
I
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
Hoving
Saske
S
Anderson
Christopher P
CP
O'Callaghan
James
J
Finch
Caleb E
CE
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004857:Equilin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology / Q000627:therapeutic use; D004970:Estrone / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D005911:Gliosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D006736:Horses; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D001057:Apolipoproteins E; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D004857:Equilin; D004970:Estrone; D004958:Estradiol; C014482:dihydroequilin