Androgen-responsive non-coding small RNAs extend the potential of HCG stimulation to act as a bioassay of androgen sufficiency.

Background: It is unclear whether a short-term change in circulating androgens is associated with changes in the transcriptome of the peripheral blood mononuclear cells (PBMC).

Aims And Methods: To explore the effect of hCG stimulation on the PBMC transcriptome, 12 boys with a median age (range) of 0.7 years (0.3, 11.2) who received intramuscular hCG 1500u on 3 consecutive days as part of their investigations underwent transcriptomic array analysis on RNA extracted from peripheral blood mononuclear cells before and after hCG stimulation.

Results: Median pre- and post-hCG testosterone for the overall group was 0.7 nmol/L (<0.5, 6) and 7.9 nmol/L (<0.5, 31.5), respectively. Of the 12 boys, 3 (25%) did not respond to hCG stimulation with a pre and post median serum testosterone of <0.5 nmol/L and <0.5 nmol/L, respectively. When corrected for gene expression changes in the non-responders to exclude hCG effects, all 9 of the hCG responders consistently demonstrated a 20% or greater increase in the expression of and , non-coding PIWI-interacting RNAs (piRNAs). In addition, of the 9 responders, 8, 6 and 4 demonstrated a 30, 40 and 50% rise, respectively, in a total of 2 further piRNAs. In addition, 3 of the responders showed a 50% or greater rise in the expression of another small RNA, . On comparing fold-change in serum testosterone with fold-change in the above transcripts, a positive correlation was detected for ( = 0.01).

Conclusions: The identification of a dynamic and androgen-responsive PBMC transcriptome extends the potential value of the hCG test for the assessment of androgen sufficiency.