title: The effects of estrogen on serum level and hepatocyte expression of PCSK9.
abstract: OBJECTIVE
  We previously reported that serum PCSK9 levels are higher in postmenopausal women than in premenopausal women in a Han Chinese population. Whether this difference is related to estrogen has not been well-characterized. This study aims to examine if the alteration in estrogen level is responsible for the changes of serum PCSK9 concentration.
  
  
  METHODS
  A sandwich ELISA assay was used to measure serum PCSK9 levels in 727 healthy women aged from 26 to 85 years old. Anthropometric and biochemical examination of parameters such as estrogen and serum lipids was also performed for these individuals. Next, we measured serum PCSK9 and estrogen levels of 30 healthy fertile women (24-26 years old) in their menstrual cycles and analyzed the correlation between serum PCSK9 level and estrogen concentration. Moreover, cell culture studies were carried out to examine if estrogen at physiological and non-physiological concentrations regulates hepatocyte PCSK9 expression.
  
  
  RESULTS
  Serum PCSK9 concentrations were significantly increased with aging. Aged group had higher serum PCSK9 levels than the middle aged group and the young group (60.29±28.47 vs 71.38±34.22 vs 83.81±33.50 ng/ml). Serum PCSK9 levels were positively correlated with age, BMI, serum total cholesterol and LDL-cholesterol (P<0.01), but not correlated with estrogen levels. There was no significantly difference of PCSK9 levels between the lower and the upper estradiol (E2) tertiles in the 727 women. There was either no significant difference in PCSK9 levels during the menstrual, ovulatory, luteal phases in the 30 healthy fertile women. Cell culture studies showed that 17β-estradiol at physiological concentrations did not significantly alter PCSK9 expression in human hepatocytes.
  
  
  CONCLUSIONS
  The serum PCSK9 levels were higher in postmenopausal women than those in pre-menopausal women. However, the difference in serum PCSK9 levels between postmenopausal and premenopausal woman appeared to be independent of estrogen status, and estrogen at physiological concentrations does not affect human hepatocyte PCSK9 expression.
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; Department of Endocrinology, Nanjing Municipal Hospital for Governmental Organizations, Nanjing 210018, China.
authors: Wen
authors: W
authors: Guo
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Jinxiang
authors: J
authors: Fu
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Xiaoli
authors: X
authors: Chen
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Beibei
authors: B
authors: Gao
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Zhenzhen
authors: Z
authors: Fu
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Hongqi
authors: H
authors: Fan
authors: Department of Geriatrics, Department of Cadres, Tong Ling People's Hospital, Tongling 244009, China.
authors: Qin
authors: Q
authors: Cui
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Xiaohui
authors: X
authors: Zhu
authors: School of Public Health Nanjing Medical University, Nanjing 210029, China.
authors: Yang
authors: Y
authors: Zhao
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
authors: Tao
authors: T
authors: Yang
authors: Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, 6439 Garners Ferry Road, Columbia, SC 29209, United States.
authors: Daping
authors: D
authors: Fan
authors: Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address: drhongwenzhou@njmu.edu.cn.
authors: Hongwen
authors: H
authors: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008593:Menopause / Q000097:blood / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: D004958:Estradiol; C472125:PCSK9 protein, human; C472126:Pcsk9 protein, mouse; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Estrogen; Low-density lipoprotein cholesterol (LDL-C); Low-density lipoprotein receptor (LDLR); Proprotein convertase subtilisin/kexin type 9 (PCSK9)