Autoregulation of cholesterol synthesis: Physiologic and pathophysiologic consequences

Autoregulation of cholesterol synthesis focuses on the 19 metabolic steps from lanosterol to cholesterol. Although synchronization of their rates of synthesis in all tissues was the paradigm, a known exception occurs in the ovary where a local increase in a sterol intermediate, FF-MAS (follicular fluid meiosis activating sterol), activates meiosis during oocyte maturation. Mutations in the genes that govern synchronization cause an increase in sterol intermediates that follow an alternate, oxysterol, pathway of metabolism. Experimental models in animals imply that oxysterol metabolites are determinants of the dysmorphism that occurs during fetal development in these genetic diseases. These few examples may portend a much broader role for sterol intermediates and their novel oxysterol metabolites in physiologic and pathophysiologic processes.

Research highlights▶ Autoregulation of cholesterol synthesis by oxysterols. ▶ Alternate pathway of metabolism for sterol intermediates in cholesterol synthesis.