Aim: 

Coronary heart disease are extremely rare in pre-menopausal women but increase at the onset of menopause: the reason of this delay is due to estrogen protective effects. The rise of cholesterolemia is one of the main risk factor for coronary disease. Since 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) is the rate limiting enzyme of the cholesterol biosynthetic pathway, plays a pivotal role in cholesterol homeostasis maintenance. Aim of this work is to investigate whether HMGR is involved in cholesterolemia rise that occurs during ageing and whether it could be consider a target for estrogen protective effects.

Methods: 

In vivo studies have been performed using as experimental model the liver of 12 month old female rats (whose estrogen level decrease is comparable to the one detected at the occurrence of human estropause), 12 month old female rats treated with 17-b-estradiol.

Results: 

The results showed a hypercholesterolemic status and a significant increase of HMGR activity according to a reduced activation of AMPK detected in 12 month old female rats with respect to controls. 17-b estradiol treatment reduced HMGR activity restoring AMPK activation.

Conclusion: 

These findings highlight the correlation between estrogen and HMGR short term regulation showing another mechanism underlying the protective role of estrogens in age-related diseases.