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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^{1, ,2}

Robert G. Elkin³, Zhihong Yan, Yuan Zhong, Shawn S. Donkin, Kimberly K. Buhman^*, Jon A. Story^*, John J. Turek, Robert E. Porter, Jr.^**, Maureen Anderson, Reynold Homan and Roger S. Newton

Department of Animal Sciences, ^* Department of Foods and Nutrition, Department of Basic Medical Sciences and ^** Department of Veterinary Pathobiology, Purdue University, West Lafayette, IN 47907 and Department of Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105.

³To whom correspondence and reprint requests should be addressed

The inability to markedly attenuate cholesterol levels in chicken eggs has led to speculation that cholesterol is essential for yolk formation and that egg production would cease when yolk cholesterol deposition was inadequate for embryonic survival. However, this critical level hypothesis remains unproven. Here, we determine the relative responsiveness of laying hens to three select inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), 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 hens for 5 wk. Liver cholesterol concentrations (mg/g tissue) were decreased (P 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 groups, while HMGR mRNA levels were unaffected. Diameters of plasma VLDL particles, the main cholesterol-carrying yolk precursor macromolecules, were reduced (P 0.05) only in hens fed 0.06% atorvastatin, and the particles contained 38% less total cholesterol (P 0.05) than controls. Plasma total cholesterol concentrations were lowered (P 0.05) by both doses of atorvastatin (-56, -63%) and simvastatin (-36,-45%). Egg cholesterol contents were maximally reduced by 46% (P 0.05), 7% (P > 0.05), and 22% (P 0.05) in hens fed the 0.06% level of atorvastatin, lovastatin, and simvastatin, respectively, while overall egg production [-19% (P 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 component for yolk formation in chickens and, as such, may be amenable to further pharmacological manipulation

KEY WORDS: • chickens • cholesterol • egg • 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors • VLDL