Circulating microRNA as a biomarker of human growth hormone administration to patients.

Circulating microRNAs (miRNAs) in plasma are being studied for use as biomarkers of specific diseases and as markers of administration of pharmaceutical agents. Administration of recombinant human growth hormone (rhGH) is prohibited by sporting authorities, but it continues to be used by athletes attempting to gain an unfair advantage in athletic competition. Current methods for detection of rhGH use rely on immunoassay technology and are limited by a short time-frame in which detection of rhGH is possible. We hypothesized that administration of rhGH would alter expression of circulating miRNAs and that any changes could be detected. To identify potential miRNA targets, we utilized miRNA microarrays for screening. Confirmatory testing used real-time reverse-transcriptase (RT) quantitative PCR (qPCR) assays of selected miRNAs in 35 plasma samples obtained from (1) individuals with no known pituitary disorders, (2) patients with excess GH production, and (3) patients receiving therapeutic replacement doses of rhGH. We identified and confirmed four miRNAs that were differentially expressed in all individuals using therapeutic replacement doses of rhGH when compared to individuals with naturally high levels of GH and normal controls. This study further develops the hypothesis that circulating miRNAs may be used as biomarkers for detection of doping in sports.