Role of endogenous and exogenous cholesterol in liver as the precursor for bile acids in rats

There is considerable evidence suggesting that compartmentalized functional pools of cholesterol in the liver contribute differently to the formation of bile acids as the precursor. The present paper deals with the incorporation of [1-¹⁴C]acetate and of [1,2-³H]cholesterol carried on lipoproteins (LDL and HDL) into biliary bile acids in perfused rat livers and bile-fistula rats. The results showed that endogenous cholesterol synthesized newly from [1-¹⁴C]acetate in the liver was incorporated into both cholic acid and chenodeoxycholic acid in a similar way, while exogenous lipoprotein-[1,2-³H]cholesterol delivered to hepatocytes from hepatic circulation was incorporated into chenodeoxycholic acid at a higher rate.     

Effect of diabetes on the metabolism of chenodeoxycholic acid in isolated perfused rat liver

The formation of alpha-muricholic acid and beta-muricholic acid from chenodeoxycholic acid was comparatively investigated in livers isolated from normal, streptozotocin-diabetic, and insulin-treated diabetic rats. [24-14C]Chenodeoxycholic acid or [24-14C]alpha-muricholic acid was infused into the perfused livers. There was no difference in biliary excretion of 14C among the different groups of rats after the infusion of each 14C-labelled bile acid. Biliary [14C]bile acids were chromatographed on a thin-layer plate and the distribution of radioactivity on the plate was measured by radioscanning. In the diabetic group, the formation ratio of alpha-muricholic acid and beta-muricholic acid from [24-14C]chenodeoxycholic acid and also that of beta-muricholic acid from [24-14C]alpha-muricholic acid were much smaller than in the normal group. Treatment of the diabetic group with insulin cancelled the difference in the infusion of each [24-14C]bile acid. The results indicate that not only 6 beta-hydroxylation of chenodeoxycholic acid to alpha-muricholic acid but also 7-epimerization of the latter acid to beta-muricholic acid is suppressed in an insulin-deficient state in rats.     

Generation of Bilateral Symmetry in the Ectoderm of the Tubifex Embryo: Involvement of Cell–cell Interactions

In embryos of the oligochaete annelid Tubifex, most ectodermal tissues are derived from four bilateral pairs of embryonic stem cells called teloblasts (ectoteloblasts N, O, P and Q). Ectoteloblasts are generated on both left and right sides of the embryo through an invariable sequence of cell divisions of a proteloblast, NOPQ, and they are positioned in a mirror symmetric pattern relative to the embryonic midline. This mirror symmetry of ectoteloblast arrangement gives rise to the generation of bilateral symmetry in the ectoderm. Here we review results of our recent experiments on Tubifex tubifex that were designed to gain an insight into the mechanisms underlying the generation of the bilaterally symmetric organization of ectoteloblasts. Cell transplantation experiments have shown that nascent NOPQ cells can be polarized according to positional information residing in the embryo. If a left NOPQ cell is transplanted to the right side of a host embryo, it exhibits polarity comparable to that of right NOPQ cells. It has also been shown that contact between NOPQ cells serves as an external cue for their polarization. Another series of cell transplantation experiments have suggested that the competence of NOPQ cells to respond to external cues becomes undetectable shortly before the production of the first teloblast (N) from the NOPQ cell. Another series of experiments utilizing cell ablation techniques have shown that teloblasts N, P and Q are specified to express the N, P and Q fates, respectively, as early as their birth. In contrast, the O teloblast and its progeny are initially pluripotent and their fate becomes restricted through inductive signals emanating from its sister P lineage. On the basis of these findings, we have proposed a model for polarization of ectodermal teloblastogenesis in the Tubifex embryo.