Regulation of hepatic apolipoprotein synthesis in the 17 alpha-ethinyl estradiol-treated rat.
Regulatory mechanisms of hepatic apolipoprotein synthesis were studied in groups of male Sprague-Dawley rats made severely hypolipidemic by treatment with pharmacological doses of 17 alpha-ethinyl estradiol. Treatment resulted in a marked reduction of plasma cholesterol and apolipoproteins B, A-I, and A-IV. Hepatic apoA-I mRNA and apoA-I synthesis were increased in the ethinyl estradiol-treated animals. Hepatic apoA-IV protein synthesis rates were unaltered; however, a reduction of the apoA-IV mRNA level was observed. Diet-control studies suggested the effects of 17 alpha-ethinyl estradiol on apoA-I, unlike those on apoA-IV, appeared to be related to the steroid and not to reduced caloric intake. Livers of control and ethinyl estradiol-treated rats synthesized both apoBH and apoBL. Total hepatic apoB (apoBL plus apoBH) synthesis and apoB mRNA levels in the ethinyl estradiol-treated rats were similar to ad libitum fed or diet-controls. In ad libitum fed and diet-control rats, 21% and 32%, respectively, of newly synthesized hepatic apoB was apoBH. In contrast, 47% of the newly synthesized apoB in the ethinyl estradiol-treated animal was apoBH. Nucleotide sequence analysis of hepatic apoB mRNA confirmed a marked decrease in the proportion of the apoBL mRNA in ethinyl estradiol-treated animals. After cessation of 17 alpha-ethinyl estradiol treatment, the hepatic apolipoprotein A-I synthesis rate, apolipoprotein A-I and A-IV mRNA levels, and the apoBH and apoBL synthesis rates, as well as plasma apolipoprotein and cholesterol levels, returned to normal. A major finding of the present study is that pharmacological doses of ethinyl estradiol do not affect total hepatic apoB synthesis, but increase the relative amount of apoBH synthesized.
Seishima
M
M
Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032.
Bisgaier
C L
CL
Davies
S L
SL
Glickman
R M
RM
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D001053:Apolipoproteins / Q000096:biosynthesis*; D001054:Apolipoproteins A / Q000378:metabolism; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000097:blood; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001055:Apolipoproteins B; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; C022205:apolipoprotein A-IV; D004997:Ethinyl Estradiol; D002784:Cholesterol