Abstract
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). 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. 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 piR-37153 and piR-39248, 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, SNORD5. On comparing fold-change in serum testosterone with fold-change in the above transcripts, a positive correlation was detected for SNORD5 (P = 0.01). The identification of a dynamic and androgen-responsive PBMC transcriptome extends the potential value of the hCG test for the assessment of androgen sufficiency.
Highlights
Sex-specific differences in anatomic, physiological and behavioural phenotypes are commonly found in many species, including humans, and are considered to be due to a combination of the effect of sex hormones and genetics [1]
Previous studies that have adopted a non-selective transcriptomic approach have shown the existence of gender-specific differences in a wide range of genes in peripheral blood mononuclear cells (PBMC) [13, 14, 15] and by studying a group of people with a wide range of conditions affecting sex development, the investigators had hypothesized that these differences were a function of programming by androgens, most likely during embryonic development [8]
We have demonstrated that there is a pattern of gene expression that can be detected in PBMC and that may be responsive to acute changes in testosterone
Summary
Sex-specific differences in anatomic, physiological and behavioural phenotypes are commonly found in many species, including humans, and are considered to be due to a combination of the effect of sex hormones and genetics [1]. Changes in circulating proteins, such as sex hormone-binding globulin (SHBG), can occur over a period of few days following androgen exposure, and this change has been used to assess androgen sensitivity, sometimes after stimulation of testosterone production with human chorionic gonadotropin (hCG) [5, 6] It is unclear whether androgens, in this context, can induce short-term changes in gene expression. It was anticipated that would this study provide valuable insight into the wider effects of androgens, but it would improve the utility of the hCG stimulation test and the diagnosis of functional androgen deficiency 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). 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
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