In vivo regulation of apolipoprotein A-I gene expression by estradiol and testosterone occurs at the translational level in inbred strains of mice.
Testosterone and estrogen alter the hepatic synthesis of apoA-I in castrated inbred strains of mice, but apoA-I mRNA levels remain unaltered, suggesting post-transcriptional regulation of apoA-I production in liver. To test this hypothesis, females of the C3H/HeJ and C57BL/6J strains of mice were castrated and after 2 weeks were given testosterone propionate (Testo 1 microgram/g body weight/day,), 17 beta-estradiol (0.16 or 5 microgram/g/day, E2L, E2H, respectively) or vehicle (placebo) for 14 days (n = 5/group). Liver polysomes were isolated from pooled livers of each group and "run-off" assays were performed. Testo increased apoA-I gene translation to 124% and 171% of controls in C3H and C57BL strains, increased polysomal mRNA levels to 276% and 438% and increased apoA-I synthesis to 181% and 269% of respective controls. Decreases in polysomal "run-off", mRNA levels and apoA-I synthesis were produced by E2H. E2L produced non-parallel changes, i.e., it raised apoA-I synthesis and polysomal apoA-I mRNA, but did not affect rates of translation. The data suggest that sex hormones exert their effects on apoA-I gene expression at the translational level.
Tang
J J
JJ
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Krul
E S
ES
Schonfeld
G
G
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D011132:Polyribosomes / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012016:Reference Values; D013045:Species Specificity; D013739:Testosterone / Q000494:pharmacology*
D016632:Apolipoprotein A-I; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol