title: Influence of physiological changes in endogenous estrogen on circulating PCSK9 and LDL cholesterol.
abstract: Pharmacologically increased estrogen levels have been shown to lower hepatic and plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels in animals and humans. We hypothesized that physiological changes in estrogen levels influence circulating PCSK9, thereby contributing to the known wide inter-individual variation in its plasma levels, as well as to the established increase in LDL cholesterol (LDL-C) with normal aging. Circulating PCSK9, estradiol, and other metabolic factors were determined in fasting samples from 206 female and 189 male healthy volunteers (age 20-85 years), The mean levels of PCSK9 were 10% higher in females than in males (P < 0.05). PCSK9 levels were 22% higher in postmenopausal than in premenopausal (P < 0.001) females. Within the group of premenopausal females, circulating PCSK9 correlated inversely to estrogen levels, and PCSK9 was higher (305 ng/ml) in the follicular phase than in the ovulatory (234 ng/ml) or the luteal (252 ng/ml) phases (P < 0.05). Changes in endogenous estrogen levels during the menstrual cycle likely contribute to the broad inter-individual variation in PCSK9 and LDL-C in normal females. PCSK9 levels increase in females after menopause but not in men during this phase in life. This likely contributes to why LDL-C in women increases in this period.
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism, and Diabetes, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden Molecular Nutrition Unit, Center for Innovative Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden Karolinska Institutet/AstraZeneca Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden.
authors.forename: Moumita
authors.initials: M
authors.lastname: Ghosh
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism, and Diabetes, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden Molecular Nutrition Unit, Center for Innovative Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gälman
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism, and Diabetes, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden Molecular Nutrition Unit, Center for Innovative Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden Karolinska Institutet/AstraZeneca Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism, and Diabetes, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden Molecular Nutrition Unit, Center for Innovative Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden Karolinska Institutet/AstraZeneca Integrated CardioMetabolic Center, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, C2-94, S-141 86 Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Angelin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D008078:Cholesterol, LDL / Q000097:blood* / Q000378:metabolism; D004967:Estrogens / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008597:Menstrual Cycle / Q000502:physiology; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000097:blood* / Q000378:metabolism; D012737:Sex Factors; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; D004967:Estrogens; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: low density lipoprotein cholesterol; menopause; menstruation cycle; proprotein convertase subtilisin/kexin type 9