title: Estrogen upregulates hepatic apolipoprotein M expression via the estrogen receptor.
abstract: Apolipoprotein M (apoM) is present predominantly in high-density lipoprotein (HDL) in human plasma, thus possibly involved in the regulation of HDL metabolism and the process of atherosclerosis. Although estrogen replacement therapy increases serum levels of apoAI and HDL, it does not seem to reduce the cardiovascular risk in postmenopausal women. Therefore, we investigated the effects of estrogen on apoM expression in vitro and in vivo. HepG2 cells were incubated with different concentrations of estrogen with or without the estrogen receptor antagonist, fulvestrant, and apoM expression in the cells was determined. Hepatic apoM expression and serum levels of apoM were also determined in normal and in ovariectomized rats treated with either placebo or estradiol benzoate, using sham operated rats as controls. Estrogen significantly increased mRNA levels of apoM and apoAI in HepG2 cell cultures in a dose- and time-dependent manner; the upregulation of both apolipoproteins was fully abolished by addition of estrogen receptor antagonist. In normal rats, estrogen treatment led to an increase in plasma lipid levels including HDL cholesterol, a marked upregulation of apoM mRNA and a significant increase in serum levels of apoM. The same pattern of regulation was found in ovariectomized rats treated with estrogen. Thus, estrogen upregulates apoM expression both in vivo and in vitro by mechanism(s) involving the estrogen receptor.
authors.affiliation: Third Affiliated Hospital of Suzhou University, Changzhou, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wei
authors.forename: Yuanping
authors.initials: Y
authors.lastname: Shi
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Feng
authors.forename: Guanghua
authors.initials: G
authors.lastname: Luo
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Qinfeng
authors.initials: Q
authors.lastname: Mu
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Tang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Lili
authors.initials: L
authors.lastname: Pan
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson-Ehle
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000037:antagonists & inhibitors / Q000097:blood; D001053:Apolipoproteins / Q000037:antagonists & inhibitors / Q000097:blood*; D000075243:Apolipoproteins M; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D004967:Estrogens / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000077267:Fulvestrant; D015870:Gene Expression / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D054834:Lipocalins / Q000037:antagonists & inhibitors / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010052:Ovariectomy; D017698:Postmenopause / Q000097:blood* / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C400523:APOM protein, human; D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D000075243:Apolipoproteins M; C521701:Apom protein, rat; D008076:Cholesterol, HDL; D004965:Estrogen Antagonists; D004967:Estrogens; D054834:Lipocalins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C074283:estradiol 3-benzoate; D000077267:Fulvestrant; D004958:Estradiol