The inhibition of neutral cholesteryl ester hydrolase by a cytosolic protein factor in female rat liver: the influence of varying hormonal and nutritional conditions on the inhibitory activity.

Abstract

A cytosolic protein, that is inhibitory to neutral cholesteryl ester hydrolase, has been investigated in the livers of female rats using microsomes isolated from the mammary gland of lactating rats as an enzyme source. To facilitate comparisons, inhibitory activity is expressed in terms of the amount (micrograms) of cytosolic protein required to reduce esterase activity by 50% and is compared to the hepatic content of both cholesterol and cholesteryl esters. The experiments revealed a sexual difference in the level of inhibitory activity, with the livers of both suckling and mature male animals containing less of the material than the corresponding females. Alterations in the physiological status of the females, such as pregnancy and lactation, led to a decrease in the activity of the protein. This was reversed by blocking lactation with a combination of an antiserum to rat growth hormone and the anti-prolactin drug, bromocriptine, but not by premature weaning of the animals. Food withdrawal for 24 hr also had the effect of increasing inhibitory activity. In general the cholesteryl ester content of the livers correlated with the level of inhibitory activity. Thus the activity of the cytosolic inhibitor of neutral cholesteryl ester hydrolase responded to changes in both the hormonal and the nutritional status of the female animal. It is suggested that the presence of the greater cholesteryl ester hydrolase inhibitory activity in the female liver may help to explain the lower risk of coronary heart disease in premenopausal females by facilitating increased hepatic storage of the sterol in the form of the ester.