title: Influence of growth hormone on circulating fibroblast growth factor 21 levels in humans.
abstract: OBJECTIVE
  Findings from animal studies indicate that growth hormone (GH) may stimulate the production of the putative metabolic regulator fibroblast growth factor 21 (FGF21). We investigated whether circulating FGF21 levels are altered in patients with GH deficiency and characterized how levels of this growth factor are influenced by acute and long-term administration of GH, and the potential relationship between FGF21 and nonesterified fatty acids (NEFAs).
  
  
  METHODS
  GH-deficient patients (n = 9) were studied prior to and during 1 year of replacement with GH. Healthy subjects (n = 8) received an intravenous bolus of GH with or without concomitant oral glucose. Healthy subjects and patients with heterozygous familial hypercholesterolaemia (n = 23) were monitored following increasing doses of GH for 3 weeks. The main outcome measures were serum FGF21 and NEFA levels. Studies were performed at two academic centres.
  
  
  RESULTS
  GH-deficient patients had FGF21 levels within the normal range, and GH replacement did not influence circulating FGF21 or NEFA concentrations. Acute GH administration to healthy control subjects did not change FGF21 levels, whereas an oral glucose load increased serum FGF21 by 25% and reduced NEFA levels by 48%. Similar effects were seen on administration of glucose together with GH. However, FGF21 levels increased dose dependently up to 3.7-fold in control subjects treated with GH for 3 weeks; simultaneously NEFA levels were increased by 47%.
  
  
  CONCLUSIONS
  GH is not critical for the maintenance of basal serum FGF21 levels in humans, but circulating FGF21 levels increase following administration of GH to healthy individuals. There is no correlation between plasma NEFA and circulating FGF21 levels.
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Department of Medicine and Molecular Nutrition Unit, Center for Biosciences, NOVUM, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Lundberg
authors.forename: C
authors.initials: C
authors.lastname: Höybye
authors.forename: T
authors.initials: T
authors.lastname: Krusenstjerna-Hafstrøm
authors.forename: H A
authors.initials: HA
authors.lastname: Bina
authors.forename: A
authors.initials: A
authors.lastname: Kharitonenkov
authors.forename: B
authors.initials: B
authors.lastname: Angelin
authors.forename: M
authors.initials: M
authors.lastname: Rudling
mesh_terms: D000704:Analysis of Variance; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009391:Nephelometry and Turbidimetry; D011863:Radioimmunoassay
chemical_list: D005230:Fatty Acids, Nonesterified; C414620:fibroblast growth factor 21; D019382:Human Growth Hormone; D005346:Fibroblast Growth Factors
keywords: FGF21; GH; NEFA; oral glucose test