title: Low-dose growth hormone administration mobilizes endothelial progenitor cells in healthy adults.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPCs) mobilize from the bone marrow secondary to a stimulus and home to sites of injury, where they differentiate into endothelial cells and contribute to the repair of damaged vasculature. We hypothesized that growth hormone (GH) administration would increase the number of circulating EPCs in adults and thereby represent a mechanism to enhance vascular health.
  
  
  METHODS
  A prospective trial of low-dose GH (0.03mg/kg/week for 4 weeks followed by 0.06mg/kg/week for a maximum of four additional weeks) in 10 healthy adults (6 males and 4 females; mean age 37 years, range 26-65). Primary outcomes measured included the number of circulating EPCs as assessed by colony-forming unit (CFU) assay and flow cytometry. Secondary outcomes included plasma measurements of known mediators of EPC mobilization and indices of nitric oxide (NO). Outcomes were measured at baseline and at study completion.
  
  
  RESULTS
  GH administration increased serum IGF-1 (143ng/mL [IQR 121-164] to 222 [IQR 194-244]; P=0.005). The increase in early-outgrowth EPCs (13 CFU per high-power field [IQR 6-24] to 19 [IQR 13-40]; P=0.005) correlated with the peak IGF-1 after adjustment for the baseline number of early-outgrowth EPCs (r=0.719 [95% CI 0.06, 0.93]; P=0.027). The number of late-outgrowth EPCs as well as CD34+, VEGFR2(KDR)+, and AC133+ cells did not significantly change. Other mediators of EPC mobilization were stable while plasma nitrite trended upwards (1.3micromol/L [IQR 0-2.5] to 3.7 [IQR 2.2-8.9]; P=0.052).
  
  
  CONCLUSIONS
  GH administration selectively augments the early-outgrowth EPC population in healthy individuals. These findings both support GH replacement in the setting of GH deficiency to maintain vascular integrity and have implications for the use of GH in future regenerative cell-based therapies. Furthermore, the decrease in EPCs observed with aging may in part be explained by the declining somatotropic axis, and thereby contribute to cardiovascular senescence.
authors.affiliation: Department of Endocrine Neoplasia and Hormonal Disorders, 1400 Holcombe Blvd. Unit 435, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, United States. jkdevin@manderson.org
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Devin
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Vaughan
authors.forename: Lewis S
authors.initials: LS
authors.lastname: Blevins
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Chen
authors.forename: Joseph
authors.initials: J
authors.lastname: Covington
authors.forename: Denise K
authors.initials: DK
authors.lastname: Verity
authors.forename: Pampee P
authors.initials: PP
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D064420:Drug-Related Side Effects and Adverse Reactions; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D006262:Health; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011446:Prospective Studies; D013234:Stem Cells / Q000187:drug effects*
chemical_list: D019382:Human Growth Hormone; D009569:Nitric Oxide