Genistein inhibits intestinal cell proliferation in piglets.
Currently 15% of U.S. infants are fed soy formulas that contain up to 14 mg of genistein equivalents/L. Our goal was to investigate the impact of dietary genistein on intestinal development. Piglets (n=8/group) were fed sow milk replacer (MR), MR+1 mg/L of genistein (LG), or MR+14 mg/L of genistein (HG) for 10 d. Formula intake, weight gain, and intestinal length and weight were similar in all groups. Average serum genistein concentration in the HG group was similar to that of soy formula-fed infants. No significant effects of genistein on enterocyte apoptosis, lactase, and sucrase activities or electrophysiologic measures were observed in jejunum or ileum. Jejunal and ileal villus heights were not significantly different, but the percentage of proliferating cell nuclear antigen-positive jejunal crypt cells in the HG was reduced 50% compared with that in MR and LG (p=0.001), indicating decreased proliferation. Enterocyte migration distance in the HG group tended to be 20% less (p=0.1) than LG or MR. Jejunal estrogen receptor beta mRNA expression in HG was half of that in LG (p=0.05), but neither was significantly different from MR. In conclusion, genistein at the level present in soy infant formula is bioactive in the small intestine and results in reduced enterocyte proliferation and migration. The lack of effect of genistein on nutrient transport and enzyme activity suggests that the impact of genistein is greater on proliferating versus differentiated intestinal cells.
Chen
An-Chian
AC
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 457 Bevier Hall, 905 S. Goodwin Avenue, Urbana, IL 61801, USA.
Berhow
Mark A
MA
Tappenden
Kelly A
KA
Donovan
Sharon M
SM
D000821:Animal Feed; D000818:Animals; D017209:Apoptosis; D000081247:CSK Tyrosine-Protein Kinase; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002853:Chromatography, Liquid; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004594:Electrophysiology; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D007082:Ileum / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D041943:Infant Formula; D007421:Intestine, Small / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D043322:Lactase / Q000378:metabolism; D013058:Mass Spectrometry; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D041942:Soy Milk; D021241:Spectrometry, Mass, Electrospray Ionization; D013393:Sucrase / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014158:Transcription, Genetic; D019061:src-Family Kinases
D017931:DNA Primers; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D012313:RNA; D004247:DNA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; D043322:Lactase; D013393:Sucrase; D053148:Caspase 3; D020169:Caspases