Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women.
OBJECTIVE
Cholesterol and lipoprotein metabolism display pronounced gender differences. Premenopausal women have lower LDL and higher HDL cholesterol, whereas men display higher synthetic rates of bile acids and cholesterol. The effects of the administration of exogenous hormones to humans and animals indicate that these gender differences can often be explained by estrogens. We evaluated how increased levels of endogenous estrogens modulate cholesterol and lipoprotein metabolism in women.


RESULTS
We studied healthy women during initiation of in vitro fertilization using blood samples obtained when endogenous estrogens were low and high. Cholesterol in VLDL and LDL, but not in HDL, was reduced 20% when estrogens were high. Apolipoprotein B levels decreased 13%. Apolipoprotein A-I and triglyceride levels increased 8% and 37%, respectively, whereas lipoprotein(a) levels were unchanged. Circulating PCSK9, a suppressor of LDL receptors, was reduced 14% when estrogens were high. Serum markers of bile acid and cholesterol synthesis were unaltered. Growth hormone levels increased 3-fold when estrogens were high, whereas insulin-like growth factor-1 and fibroblast growth factor-21 concentrations were unaltered.


CONCLUSIONS
In women, Apolipoprotein B-containing particles and circulating PCSK9 are reduced when endogenous estrogens are high, indicating that endogenous estrogens induce hepatic LDL receptors partly through a posttranscriptional mechanism. However, estrogens do not stimulate bile acid or cholesterol synthesis.
Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Karolinska Institute at Karolinska University Hospital Huddinge S-141 86 Stockholm, Sweden.
Lena
L
Persson
Peter
P
Henriksson
Eli
E
Westerlund
Outi
O
Hovatta
Bo
B
Angelin
Mats
M
Rudling
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002064:Buserelin / Q000008:administration & dosage; D008078:Cholesterol, LDL / Q000097:blood*; D015536:Down-Regulation; D004958:Estradiol / Q000097:blood*; D005260:Female; D005300:Fertility Agents, Female / Q000008:administration & dosage; D005307:Fertilization in Vitro; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D010062:Ovulation Induction; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood*; D012697:Serine Endopeptidases / Q000097:blood*; D013548:Sweden
D001055:Apolipoproteins B; D001647:Bile Acids and Salts; D015415:Biomarkers; D008078:Cholesterol, LDL; D005300:Fertility Agents, Female; D017270:Lipoprotein(a); D019382:Human Growth Hormone; D004958:Estradiol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D002064:Buserelin