Table 2 Sexual dimorphisms in mice lacking enzymes that participate in formation of bile acids with clinical phenotypes in humans (differences between sexes not considered in these studies)
From: The influence of biological sex and sex hormones on bile acid synthesis and cholesterol homeostasis
Bile Acid Synthetic Enzyme | Phenotype in knockout in terms of BAs & cholesterol | Human phenotype when gene is mutated |
|---|---|---|
CYP7A1 | Lithogenic composition of gallstones with increased dietary cholesterol in females [30] | Statin-resistant hypercholesterolemia [28] |
BA pool - larger in females [30] | ||
BA pool composition - higher CA in females [30] | ||
Hepatic cholesterol accumulation with increased dietary cholesterol in females (males not reported) [31] | 94% reduction in fecal BA excretion [28] | |
Maternal consumption of high fat diet results in male offspring with lower expression than females [33] | Premature atherosclerosis [28] | |
CYP8B1 | BA pool increases in male more dramatically than in females [3] | Â |
Greater compensatory response by CYP7A1 in female knockout, resulting in increased CDCA [3] | ||
CYP27A1 | Cerebrotendinous xanthomatosis [55] | |
Vascular and muscle cholesterol deposition [60] | ||
ARK1D1 | Higher hepatic BA concentration and lean phenotype in males [69] | Â |
CYP3A4 | Sex differences not reported in genome-edited rats [75] | Â |