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

Rodie, M.E., Mudaliar, M.A.V. , Herzyk, P. , McMillan, M., Boroujerdi, M., Chudleigh, S., Tobias, E.S. and Ahmed, S.F. (2017) Androgen-responsive non-coding small RNAs extend the potential of HCG stimulation to act as a bioassay of androgen sufficiency. European Journal of Endocrinology, 177(4), pp. 339-346. (doi: 10.1530/EJE-17-0404) (PMID:28733293)

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Abstract

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 & Methods: To explore the effect of hCG-stimulation on the PBMC-transcriptome, 12 boys with a median age (range) of 0.7yrs (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 0.7nmol/l (<0.5,6) and 7.9nmol/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 <0.5nmol/l and <0.5nmol/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). Conclusions: The identification of a dynamic and androgen-responsive PBMC-transcriptome extends the potential value of the hCG test for assessment of androgen sufficiency.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McMillan, Dr Margaret and Rodie, Dr Martina and Tobias, Professor Edward and Mudaliar, Dr Manikhandan and Herzyk, Dr Pawel and Ahmed, Professor Syed Faisal and Boroujerdi, Dr Massoud
Authors: Rodie, M.E., Mudaliar, M.A.V., Herzyk, P., McMillan, M., Boroujerdi, M., Chudleigh, S., Tobias, E.S., and Ahmed, S.F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > MRC/CSO SPHSU
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:European Journal of Endocrinology
Publisher:BioScientifica
ISSN:0804-4643
ISSN (Online):1479-683X
Published Online:21 July 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in European Journal of Endocrinology 177(4): 339-346
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS