Estrogen deficiency reduces estrogen receptor-alpha (ERα) and promotes apoptosis in the hippocampus, inducing learning-memory deficits; however, underlying mechanisms remain less understood.
More recently, the role of estrogen in men was uncovered by prismatic examples of estrogen deficiency in male patients and by knockout of the estrogen receptor and aromatase in animals.
The overall findings obtained with the rat model of menopause highlight the importance of dietary consumption of C. esculenta constituents as potential selective estrogen receptor modulators and suggest that they may prevent some of the metabolic disorders related to estrogen deficiency.
The generation of the aromatase knockout (ArKO) and estrogen receptor knockout (ERKO) mouse models has enabled researchers to characterize the effects of complete estrogen deficiency within the brain and hence behavior.
These findings were replicated in wild-type N2a cells treated with Abeta25-35, and to a relatively larger extent, in both wild-type N2a cells and APPswe treated by okadaic acid, as well as in the brains of estrogen receptor (ER) alpha-/- and ERbeta-/- mice that mimic the status of estrogen deficiency in menopausal AD patients.
These data thus indicate that the ER-alpha genotype may modulate the relationship between BMD or rates of bone loss and estrogen levels in men and that bone mass in men with the X or P alleles may be more susceptible to the consequences of estrogen deficiency (and conversely, benefit most from estrogen sufficiency) than in men with the xx or pp genotypes.
Estrogen receptor (ER) alpha is expressed during osteoblast differentiation; however, both its functional role in bone metabolism and its involvement in osteoporotic pathogenesis caused by estrogen deficiency are not well understood.