27-Hydroxycholesterol, does it exist? On the nomenclature and stereochemistry of 26-hydroxylated sterols.

Significant ambiguity exists in the scientific community with regard to the nomenclature of 26-hydroxylated oxysterols. Oxysterols constitute an important class of compounds that have biological roles in the regulation of cholesterol synthesis and as endogenous selective estrogen receptor modulators (SERMs). The ambiguity is attributable to deviations from clearly stated IUPAC rules and is likely to increase as more biologically active oxysterols are identified. This review provides a uniform approach to the naming of 26-hydroxylated sterols for those of current interest and for those on the horizon such as oxysterols of lanosterol that retain the unsaturation at C-24 and C-25 such as (E)-26-hydroxylanosterol. Using this molecule as a starting point, this review hopes to establish a common language to keep all investigators on the same page.

Ambient temperature as a contributor to kidney stone formation: implications of global warming.

Nephrolithiasis is a common disease across the world that is becoming more prevalent. Although the underlying cause for most stones is not known, a body of literature suggests a role of heat and climate as significant risk factors for lithogenesis. Recently, estimates from computer models predicted up to a 10% increase in the prevalence rate in the next half century secondary to the effects of global warming, with a coinciding 25% increase in health-care expenditures. Our aim here is to critically review the medical literature relating stones to ambient temperature. We have categorized the body of evidence by methodology, consisting of comparisons between geographic regions, comparisons over time, and comparisons between people in specialized environments. Although most studies are confounded by other factors like sunlight exposure and regional variation in diet that share some contribution, it appears that heat does play a role in pathogenesis in certain populations. Notably, the role of heat is much greater in men than in women. We also hypothesize that the role of a significant human migration (from rural areas to warmer, urban locales beginning in the last century and projected to continue) may have a greater impact than global warming on the observed worldwide increasing prevalence rate of nephrolithiasis. At this time the limited data available cannot substantiate this proposed mechanism but further studies to investigate this effect are warranted.

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.