We have reported that GH and Insulin-like Growth Factor I (IGF-I) diminished T3-specific metabolic actions in rat by lessening TR expression. Somatic growth depends on GH, IGF-I and triiodothyronine (T3) status. In growth disorders, GH or IGF-I are administered to correct final height. However, the growth response to GH/IGF-I in some patients is below that which is expected. Such failure may be due to a reduced TR expression and thus, a lesser T3-tissue action in tissues such as bone. In TS patients, GH treatment improves the adult height, although some of them fail. TR are expressed in PBMC at low levels. Since blood collection is feasible, assessment of TR mRNA expression in PBMC from patients under GH or IGF-I treatment may be a tool to follow up the outcome of the therapy. The aim of this study was: 1) to set up a non-radioactive method for TR mRNA semiquantification in PBMC to be applied in clinical laboratories; and 2) to analyze PBMC TR mRNA levels in patients treated with GH: PBMC were purified from 5-15 yr female patients (10 normal, 10 TS under GH treatment (1U/kg/week) for at least 6 mo and 10 no-GH treated TS), by ficoll-hypaque and total RNA extracted. TR and GADPH mRNAs were measured in parallel by RT-PCR. PCR products were resolved in agarose and visualized by etidium bromide staining and densitometrically scanned. Results: 1) A reliable sensitive non-radioactive semiquantification of TR mRNA was set up. 2) TR mRNA was significantly reduced in TS patients under GH treatment vs. no-treated TS patients (p<0.01, ANOVA/Student-Neuman-Keuls). Non-significant differences were obtained between normal and no-treated TS patients.

Conclusions of the Abstract

Results indicate that the method we have set up is suitable to semiquantify TR mRNA from PBMC. In TS patients, GH treatment reduced TR expression in PBMC. The effect of GH on TR mRNA would also account for TR expression in bone cells leading to a reduced T3 action, and a failure to properly respond to GH therapy is possible to be predicted.