Androgen receptor expression is required to ensure development of adult Leydig cells and to prevent development of steroidogenic cells with adrenal characteristics in the mouse testis

O'Shaughnessy, P. J. , Mitchell, R. T., Monteiro, A., O'Hara, L., Cruickshanks, L., Claahsen-van der Grinten, H., Brown, P., Abel, M. and Smith, L. B. (2019) Androgen receptor expression is required to ensure development of adult Leydig cells and to prevent development of steroidogenic cells with adrenal characteristics in the mouse testis. BMC Developmental Biology, 19, 8. (doi: 10.1186/s12861-019-0189-5) (PMID:30995907) (PMCID:PMC6472051)

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Abstract

Background: The interstitium of the mouse testis contains Leydig cells and a small number of steroidogenic cells with adrenal characteristics which may be derived from the fetal adrenal during development or may be a normal subset of the developing fetal Leydig cells. Currently it is not known what regulates development and/or proliferation of this sub-population of steroidogenic cells in the mouse testis. Androgen receptors (AR) are essential for normal testicular function and in this study we have examined the role of the AR in regulating interstitial cell development. Results: Using a mouse model which lacks gonadotropins and AR (hpg.ARKO), stimulation of luteinising hormone receptors in vivo with human chorionic gonadotropin (hCG) caused a marked increase in adrenal cell transcripts/protein in a group of testicular interstitial cells. hCG also induced testicular transcripts associated with basic steroidogenic function in these mice but had no effect on adult Leydig cell-specific transcript levels. In hpg mice with functional AR, treatment with hCG induced Leydig cell-specific function and had no effect on adrenal transcript levels. Examination of mice with cell-specific AR deletion and knockdown of AR in a mouse Leydig cell line suggests that AR in the Leydig cells are likely to regulate these effects. Conclusions: This study shows that in the mouse the androgen receptor is required both to prevent development of testicular cells with adrenal characteristics and to ensure development of an adult Leydig cell phenotype.

Item Type:Articles
Additional Information:Also funded by the Medical Research Council MR/N002970/1.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Monteiro, Dr Ana and O'Shaughnessy, Professor Peter
Authors: O'Shaughnessy, P. J., Mitchell, R. T., Monteiro, A., O'Hara, L., Cruickshanks, L., Claahsen-van der Grinten, H., Brown, P., Abel, M., and Smith, L. B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:BMC Developmental Biology
Publisher:BioMed Central
ISSN:1471-213X
ISSN (Online):1471-213X
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in BMC Developmental Biology 19:8
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
413101Testicular function in mice lacking sertoli cell androgen receptors and FSH receptorsPeter O'ShaughnessyWellcome Trust (WELLCOTR)078137/Z/05/ZRI BIODIVERSITY ANIMAL HEALTH & COMPMED