Oral contraceptives decrease hepatic cholesterol independent of the LDL receptor in nonhuman primates.
Pharmacological doses of estrogens have been reported to increase hepatic catabolism of low-density lipoprotein (LDL) by the LDL receptor (LDL-R) pathway and to increase the concentration of mRNA for the LDL receptor. The induction of LDL-Rs by large doses of estrogen may not be relevant to the role of estrogens under physiological conditions. Furthermore, the mechanisms by which oral contraceptives, a combination of synthetic estrogen and progestin, may modulate LDL metabolism remain largely unexplored. Adult female cynomolgus monkeys were given combination ethinyl estradiol/norgestrel preparations (n = 16) for 16 weeks and were compared with a control group that did not receive exogenous sex hormones (n = 7). All animals consumed a diet containing 0.25 mg cholesterol/kcal with 40% of calories from saturated fats. After 16 weeks of treatment there was no significant difference in LDL cholesterol (LDL-C) and hepatic LDL-R mRNA concentration between oral contraceptive-treated animals (LDL-C, 242 +/- 113 mg/dL; LDL-R mRNA, 0.60 +/- 0.31 pg/microgram RNA) and control animals (LDL-C, 277 +/- 100 mg/dL; LDL-R mRNA, 0.51 +/- 0.21 pg/microgram RNA). In contrast, the hepatic cholesteryl ester concentration was significantly lower in the oral contraceptive-treated animals (7.28 +/- 3.59 mg/g liver) compared with the control animals (16.07 +/- 11.86 mg/g liver; P = .01) with no significant difference in hepatic free cholesterol concentration between the groups. Thus, oral contraceptives decrease hepatic cholesterol concentration independent of LDL-R expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Colvin
P L
PL
Department of Compartive Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC. 27157.
Wagner
J D
JD
Heuser
M D
MD
Sorci-Thomas
M G
MG
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008252:Macaca fascicularis; D009644:Norgestrel / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011973:Receptors, LDL / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D003278:Contraceptives, Oral, Hormonal; D012333:RNA, Messenger; D011973:Receptors, LDL; D009644:Norgestrel; D004997:Ethinyl Estradiol; D002784:Cholesterol