Select 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors vary in their ability to reduce egg yolk cholesterol levels in laying hens through alteration of hepatic cholesterol biosynthesis and plasma VLDL composition

The inability to markedly attenuate cholesterol levels in chicken eggs has led to speculation that cholesterol is essential for yolk formation and tha t egg production would cease when yolk cholesterol deposition was inadequat e for embryonic survival. However, this critical level hypothesis remains u nproven. Here, we determine the relative responsiveness of laying hens to t hree select inhibitors of 5-hydroxy3-methylglutaryl-coenzyme A reductase (H MGR), the rate-limiting enzyme of cholesterol biosynthesis. A control diet, either alone or supplemented with one of two dietary levels (0.03 or 0.06% ) of atorvastatin, lovastatin, or simvastatin, was fed to White Leghorn hen s for 5 wk. Liver cholesterol concentrations (mg/g tissue) were decreased ( P less than or equal to: 0.05) by each HMGR inhibitor; however, total liver cholesterol (mg) did not differ among treatments. Microsomal hepatic HMGR activities were increased one- to twofold in all HMGR inhibitor-treated gro ups, while HMGR mRNA levels were unaffected. Diameters of plasma VLDL parti cles, the main cholesterol-carrying yolk precursor macromolecules, were red uced (P less than or equal to 0.05) only in hens fed 0.06% atorvastatin, an d the particles contained 38% less total cholesterol (P less than or equal to 0.05) than controls. Plasma total cholesterol concentrations were lowere d (P less than or equal to 0.05) by both doses of atorvastatin (-56, -63%) and simvastatin (-36,-45%). Egg cholesterol contents were maximally reduced by 46% (P less than or equal to 0.05), 7% (P > 0.05), and 22% (P less than or equal to 0.05) in hens fed the 0.06% level of atorvastatin, lovastatin, and simvastatin, respectively, while overall egg production [-19% (P less than or equal to 0.05), +4% (P > 0.05), and -3% (P > 0.05)], was much less affected. We concluded that cholesterol per se may not be an obligatory com ponent for yolk formation in chickens and, as such, may be amenable to furt her pharmacological manipulation.