Abstract

BackgroundThe 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.ResultsUsing 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.ConclusionsThis 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.

Highlights

  • 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

  • Results hCG-induced Leydig cell hyperplasia in the hpg mouse is dependent on androgen receptors Treatment with human chorionic gonadotropin increased testicular volume (Table 1) and caused an 8 to10-fold increase in total Leydig cell number (Fig. 1) in both hpg and hpg.SCARKO mice compared to untreated animals

  • Expression of transcript/proteins common to most steroidogenic cells is unaffected by the absence of androgen receptors Expression of Hsd3b1 and Por transcripts was relatively high in untreated hpg, hpg.SCARKO and hpg.ARKO mice and showed little response to hormone treatment (Fig. 2a)

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Summary

Introduction

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. It is not known what regulates development and/or proliferation of this sub-population of steroidogenic cells in the mouse testis. After the split of the adreno-gonadal primordium the fetal population of Leydig cells develops in the testicular interstitium and so it is possible that some or all of the adrenal-like cells may be a normal sub-population of the developing Leydig cells [10,11,12]. Development of the adult Leydig cell population is very largely dependent upon the action of luteinising hormone (LH) but it is not clear why the testicular adrenal cells do not show further development since they respond to LH [9]

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