Differences in de novo cholesterol synthesis between the intact male and female rat

Three different isotopes were used to quantify de novo sterologenesis in intact male and female rats. All three substrates (i.e. [14C]acetate, [14C]octanoate, and [3H]water) were incorporated into nonsaponifiable lipids and cholesterol at significantly greater rates in males than in females. Even with cholesterol feeding, male animals synthesized significantly more cholesterol and nonsaponifiable lipids than females. The primary site of this sex difference in sterologenesis is extrahepatic, extraintestinal tissues (e.g. carcass). In the carcass this sex difference is chiefly due to an enhancement of sterol synthesis in the skin of male rats. Cholesterol synthesis is 73% greater and nonsaponifiable lipid synthesis is 85% greater in the skin of males than in females. Moreover, de novo sterologenesis in skin is hormonally dependent. In castrated females, testosterone treatment results in a 2-fold stimulation of skin sterol synthesis compared to that in animals administered estradiol or oil vehicle alone. In castrated males, estradiol treatment caused a 30% reduction in skin cholesterol and nonsaponifiable lipid synthesis compared to that in animals administered testosterone. The effects of sex steroid hormones on skin are, therefore, probably responsible for mediating the observed sex difference in de novo sterol synthesis. Additionally, this study demonstrates that the administration of estradiol and testosterone in physiological doses to castrated animals has no effect on cholesterol or nonsaponifiable lipid synthesis in liver, intestine, or other nondermal tissues.