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.
Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032.
M
M
Seishima
C L
CL
Bisgaier
S L
SL
Davies
R M
RM
Glickman
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