Estrogen deficiency results in apoptosis in the frontal cortex of adult female aromatase knockout mice.
The aromatase knockout (ArKO) mouse is completely estrogen deficient. We previously detected apoptosis in the hypothalamus of 1 year-old male ArKO mice. This study shows that 12 week-old female ArKO mice display spontaneous apoptosis of pyramidal neurons in the frontal cortex while wild-type (WT) littermates show no signs of apoptosis. Concomitantly, bcl-2 related anti-apoptotic genes are down-regulated whereas the pro-apoptotic gene TRADD is up-regulated in the female ArKO frontal cortex. This phenotype can be rescued by 3-week replacement of 17beta-estradiol. Furthermore, the apoptosis phenotype is exacerbated in 12-15 month-old female ArKO mice, which have 30% less neurons in the frontal cortex and lower brain weights than WT counterparts. These data show that estrogens are essential for the survival of female cortical neurons even in the absence of pathological conditions or external assaults. Our observations also demonstrate the sexually dimorphic susceptibility of neurons to estrogen deficiency.
Hill
Rachel A
RA
Prince Henry's Institute of Medical Research, Clayton, VIC 3168, Australia.
Chua
Hui Kheng
HK
Jones
Margaret E E
ME
Simpson
Evan R
ER
Boon
Wah Chin
WC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D004268:DNA-Binding Proteins; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D009929:Organ Size
D004268:DNA-Binding Proteins; D004967:Estrogens; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D004958:Estradiol; D001141:Aromatase; D053148:Caspase 3