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)

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 > School of Biodiversity, One Health & Veterinary 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
41310	1	Testicular function in mice lacking sertoli cell androgen receptors and FSH receptors	Peter O'Shaughnessy	Wellcome Trust (WELLCOTR)	078137/Z/05/Z	RI BIODIVERSITY ANIMAL HEALTH & COMPMED