Zeranol enhances the proliferation of pre-adipocytes in beef heifers.
BACKGROUND
The high morbidity and mortality of breast cancer among women is a serious problem. The adverse effects of the consumption of beef with zeranol (Z, a growth promoter widely used in beef industry in North American) residue on human health are still unknown.


METHODS
The effects of Z implantation on the growth of heifer pre-adipocytes were evaluated. The stimulatory effects of Z and estradiol-17beta (E(2)) on the proliferation of pre-adipocytes isolated from control heifers and Z-implanted heifers were measured. Real-time PCR and Western-blotting analysis were performed to evaluate the expression of cyclin D1 and p53 at both mRNA and protein levels.


RESULTS
The growth of pre-adipocytes from heifers bearing for 2 months of Z-implants was about 12-fold faster than that observed in control heifers. The pre-adipocytes isolated from Z-implanted heifers were more sensitive to treatment with Z and E(2). Z up-regulated the expression of cyclin D1 and down-regulated p53 in pre-adipocytes isolated from Z-implanted heifers.


CONCLUSIONS
The implantation of Z increases body weight gain by enhancing growth of pre-adipocytes. The stimulation of pre-adipocytes division by Z and E(2) might be partially mediated by up-regulation of cyclin D1 and down-regulation of p53 at mRNA and protein levels.
Ye
Weiping
W
Laboratory of Reproductive and Molecular Endocrinology, Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus, OH 43210, USA.
Xu
Pingping
P
Threlfall
Walter R
WR
Jen
Robert
R
Li
Hong
H
Lin
Shu-Hong
SH
Kuo
Cheik-Ti
CT
Lin
Young C
YC
D017667:Adipocytes / Q000187:drug effects*; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002417:Cattle / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects; D015029:Zeranol / Q000008:administration & dosage / Q000494:pharmacology*
D004968:Estrogens, Non-Steroidal; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D004958:Estradiol; D015029:Zeranol