title: 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.
abstract: The aromatase (ArKO) knockout mouse is estrogen deficient. Our previous analysis revealed apoptosis of dopaminergic neurons in the arcuate nucleus (Arc) 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 16alpha-LE(2) (ERalpha-specific agonist) or 8beta-VE(2) (ERbeta-specific agonist). Daily injections (6 weeks) with 16alpha-LE(2) prevented dopaminergic cell death in the Arc of male ArKO mice, with no significant effect of 8beta-VE(2) treatment. In contrast, 8beta-VE(2) prevented dopaminergic cell death in the MPO, while 16alpha-LE(2) had no significant effect. Concomitant decreases in Fas and FasL protein levels were found upon 16alpha-LE(2) and 8beta-VE(2) treatment in the Arc 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.
authors: Prince Henry's Institute, Clayton 3168, VIC, Australia.
authors: Rachel A
authors: RA
authors: Hill
authors: Jenny
authors: J
authors: Chow
authors: Karlheinrich
authors: K
authors: Fritzemeier
authors: Evan R
authors: ER
authors: Simpson
authors: Wah Chin
authors: WC
authors: Boon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D001141:Aromatase / Q000172:deficiency*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000502:physiology*; D053222:Fas Ligand Protein / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011301:Preoptic Area / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D001141:Aromatase; D014446:Tyrosine 3-Monooxygenase; D053148:Caspase 3; D053181:Caspase 8