Promegestone (R5020) and mifepristone (RU486) both function as progestational agonists of human glycodelin gene expression in isolated human epithelial cells.

One of the most abundant protein products of human secretory endometrium is glycodelin, a glycoprotein previously referred to as PP14. Although the precise function of this protein is unknown, its unique glycosylation pattern is believed to affect immunomodulatory activity during human embryonic implantation and inhibition of sperm-egg binding after ovulation. Having confirmed the expression of glycodelin in secretory endometrial glands, we used purified endometrial epithelial cell cultures to demonstrate the hormonal regulation of glycodelin synthesis and secretion. The findings were corroborated by transiently transfecting glycodelin gene promoter-reporter constructs into human epithelioid HeLa and Ishikawa cells. Our results indicate that glycodelin protein production by endometrial epithelial cells is directly up-regulated 4- to 9-fold by progestins and antiprogestins in vitro. Transcriptional regulation of the glycodelin gene promoter expressed in HeLa cells is progesterone receptor-dependent. As observed in the primary endometrial cells, progestins and antiprogestins both act as agonists on the in vitro expression of this endometrial gene. Our findings provide insight into the regulation of this abundant endometrial protein and raise interesting questions about the physical nature of the interaction of agonist- and antagonist-bound progesterone receptors with the glycodelin gene promoter.

Effect of pectin, wheat bran and cellulose on serum lipids and lipoproteins in rats fed on a low- or high-fat diet.

1. Four groups of adult male Sprague-Dawley rats were fed for 6 weeks on a diet with a low-fat content (50 g/kg) and another four groups were given a diet rich in fat (250 g/kg) and cholesterol (12 g/kg). In both cases, the basal diets were either fibre-depleted or supplemented with cellulose (60 g/kg), wheat bran (100 g/kg) or low-methoxyl pectin (100 g/kg). 2. Low-methoxyl pectin displayed the most hypocholesterolaemic effect and decreased the cholesterol content of the very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL), when the low-fat diet was given. When rats were fed on the high-fat diet, pectin no longer had a hypocholesterolaemic effect but still decreased the VLDL-cholesterol content. Pectin lowered serum triglyceride and VLDL-triglyceride levels only when the low-fat diet was given. 3. Wheat bran exerted no hypocholesterolaemic effect in rats fed on the low- and high-fat diets, but decreased the cholesterol content of VLDL and lowered serum triglycerides and VLDL-triglycerides when the high-fat diet was given. 4. Purified cellulose had no significant effect on plasma lipids. 5. As shown by multivariance analysis, low-methoxyl pectin and wheat bran both beneficially modified the serum triglyceride and cholesterol variables except VLDL-triglycerides. However, the magnitude of the effect of each individual type of fibre was dependent on the fat and cholesterol content of the diet, suggesting the existence of different mechanisms of action.

Effects of dietary fibers and cholestyramine on the activity of pancreatic lipase in vitro.

Most experiments were conducted in the presence of human gallbladder bile; colipase and pancreatic lipase were purified using porcine pancreas. The adsorption of bile salts, phospholipids and cholesterol from the bile, together with that of pancreatic lipase was measured on wheat bran, cellulose, hemicellulose (xylan), slightly methylated pectin (42%) and cholestyramine. In contrast to cholestyramine which intensively binds biliary lipids (61.7-81.7%) and pancreatic lipase (47.5%), the fibers studied only had a low adsorbent power. The direct influence of these fibers and of cholestyramine at concentrations ranging from 0-5% on lipase activity was measured at constant pH, using two conventional assay systems, long chain triglycerides and tributyrin. In the presence of human bile and colipase, a drastic reduction in triglyceride hydrolysis by lipase was observed with cholestyramine (loss of 66-82%) and wheat bran (loss of 77-94%) at 1% concentration. The other fibers did not have any marked effects on enzyme activity. The use of a radio labeled lipase made it possible to demonstrate that the inhibitory effect of bran on enzyme activity was independent of adsorption phenomena on bran. The fraction of bran that can be solubilized in the aqueous phase, in fact, induced this reduction in activity. The presence of protein inhibitor in bran may be responsible for the reduction in pancreatic lipase activity.

Effect of wheat bran, pectin and cellulose on the secretion of bile lipids in rats.

We assayed the lipid content of bile from rats that had been fed either a standard diet (5% fat) or a high fat diet (25% fat, 1.2% cholesterol) in the presence or in the absence of various dietary fibers (namely, wheat bran, pectin and cellulose). The cholesterol concentration in bile from rats fed the high fat diet plus wheat bran or pectin was lower than that of the rats fed the high fat, high cholesterol diet without fiber. Bile phospholipids did not vary significantly from one group to another. In comparison to the standard diet, the high fat, high cholesterol diet led to a greater ratio of primary to secondary bile salts and a higher level of glycoconjugates. The observed differences may be explained by a variation in the metabolism of bile salts brought about by the difference in diet.