equilin and Brain-Injuries

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.

Topics: Animals; Apolipoproteins E; Astrocytes; Brain; Brain Injuries; Cells, Cultured; Coculture Techniques; Dose-Response Relationship, Drug; Equilin; Estradiol; Estrogens; Estrogens, Conjugated (USP); Estrone; Glial Fibrillary Acidic Protein; Gliosis; Horses; Nerve Regeneration; Neuronal Plasticity; Neuroprotective Agents; Rats; RNA, Messenger; Up-Regulation