Fas/FasL-mediated apoptosis in the arcuate nucleus and medial preoptic area of male ArKO mice is ameliorated by selective estrogen receptor alpha and estrogen receptor beta agonist treatment, respectively

摘要

The aromatase (ArKO) knockout mouse is estrogen deficient. Our previous analysis revealed apoptosis of dopaminergic neurons in the arcuate nucleus (Are) and medial preoptic area (MPO) of 1-year-old male ArKO mice. We sought to determine which estrogen receptor (ER) is involved in the anti-apoptotic action of estrogen. Male ArKO (9.5-month-old) mice were treated with 16 alpha-LE2 (ER alpha-specific agonist) or 8 beta-VE2 (ER beta-specific agonist). Daily injections (6 weeks) with 160(LE, prevented dopaminergic cell death in the Arc of male ArKO mice, with no significant effect of 8 beta-VE2 treatment. In contrast, 8 beta-VE2 prevented dopaminergic cell death in the MPO, while 16ot-LE had no significant effect. Concomitant decreases in Fas and FasL protein levels were found upon 16 alpha-LE2 and 8 beta-VE2 treatment in the Are and MPO, respectively. Our results indicate that anti-apoptotic effects of estrogen are ER mediated, and the specific ER subtype involved in regulating apoptosis depends on the particular brain nucleus in question. (c) 2007 Elsevier Inc. All rights reserved.