The human colonic microflora influences the alterations of xenobiotic-metabolizing enzymes by catechins in male F344 rats.

As other xenobiotics, polyphenols are metabolized both by the endogenous detoxication system and the gut microflora. We hypothesized that the presence of a gut microflora may account for the effect of catechins on phase I and II xenobiotic-metabolizing enzymes and that the human bacterial metabolites may be different from those of a rodent gut microflora. Therefore, the effects of 2% (+)-catechin or 2% (-)-epicatechin were studied in germ free (GF) rats and rats inoculated with the flora of a human volunteer (HFA). In addition, the catechins were administered in ethanol as a vehicle. In the liver, (+)-catechin or (-)-epicatechin decreased the total amount of CYP450 in both GF and HFA rats while the isoenzyme CYP2E1 decreased. In GF rats only, CYP2C11 increased when compared to the rats treated with the vehicle alone. (+)-catechin increased the specific activity of UGT-chloramphenicol in GF rats only and that of cytosolic glutathion-S-transferase (GST) in HFA rats only. In the intestine, (+)-catechin and (-)-epicatechin increased the specific activity of UGT-4-methylumbelliferone in both GF and HFA rats and that of UGT- chloramphenicol in HFA rats only. In conclusion, the presence of a human flora in rats is able to modify the inducing effect of catechins on the UGT and GST activities suggesting the involvement of bacterial metabolites. The alterations on CYP 450 are independent of the presence of a human gut flora.

Growth hormone-binding protein in the goat: characterization, evolution under exogenous growth hormone treatment, and correlation with liver growth hormone receptor levels.

This report describes the identification and characterization of a specific, high-affinity growth hormone-binding protein (GHBP) in lactating goat serum. Serum samples were incubated with [125I]human GH as ligand and in the absence or in the presence of bovine GH as competitor. GH-GHBP complex formation was performed by high-performance liquid chromatography, and the radioactivity was recorded on-line with a Berthold LB detector connected to a computer. The results showed that a serum protein was able to bind specifically to human GH and bovine GH but not to ovine prolactin. Scatchard plots indicated an affinity constant of 4.5 x 10(8) M-1 and a maximum binding capacity of 4.8 x 10(-10) mol/l. In addition, we conducted a 4-wk study to determine the effects of recombinant bovine GH administration on milk production in lactating goats. The effects of recombinant bovine GH treatment on milk production and on the regulation of GHBP and hepatic GH receptor levels were studied. As expected, recombinant bovine GH injected daily increased yields of milk, fat, protein (40, 61, and 40%, respectively), and circulating insulin-like growth factor 1 concentrations compared with controls. During the pretreatment and treatment periods, the control goats exhibited a constant amount of GHBP in serum. No consistent effect of GH treatment on GHBP level was observed. The binding of [125I]bovine GH to hepatic microsomal membranes of GH-treated goats was significantly decreased compared with that of control goats. After MgCl2 desaturation of membranes, the results demonstrated that the down-regulation of GH hepatic receptors, observed for the treated goat group, was induced by receptor occupancy without modification of binding affinity. The GH receptor gene expression, analyzed by slot blot and hybridization with an [alpha-32P]GH receptor cDNA probe, was not modified by the GH treatment. In lactating goats, the galactopoietic effect of exogenous GH involved a hepatic receptor occupancy. The individual concentration of GHBP in serum cannot explain the individual variations of responses to GH treatment in goats.