Circulating Nucleic Acids in the Assessment of Endogenous Growth Hormone Production

Abstract

There is growing concern about the use of recombinant human growth hormone (rhGH) by individuals taking part in competitive sports. Although rhGH is banned by the international organizations, the detection of GH doping is difficult. We postulated that rhGH will suppress endogenous GH production, which can be assessed by the measurement of mRNA for GH and growth hormone-releasing hormone (GHRH). In order to prove this concept, we undertook a pilot study to examine whether circulating nucleic acids are useful in the detection of endogenous GH production. Blood samples were collected into PAXgene tubes from 37 healthy controls and 12 acromegalic patients. RNA was extracted from the samples, cDNA was obtained, and the quantities of mRNA for GH and GHRH were measured using real-time PCR. In acromegalic patients, median mRNA concentration for GHRH (corrected for beta-actin mRNA) was 30.7 times lower than in controls (median delta C(T)) value of -0.128 versus 3.927, P < 0.001). There was a significant correlation between serum IGF-1 SD score and mRNA for GHRH (r= 0.407). In acromegalic patients, mRNA for GH was significantly higher than in controls (median values of -4.694 versus -0.044, P < 0.05). As GH production is known to decline with age, we also examined mRNA for GH and GHRH according to age subgroups. Both markers were significantly lower in the older age group (>50 years) compared to the younger age group (<34 years). These results show that mRNA for GH and GHRH can be detected in the peripheral circulation and raises the possibility of using these markers in the detection of exogenously administered GH.