Dexamethasone suppresses the differentiation of stem Leydig cells in rats in vitro

Zhang Jingwei †,
Hu Guanghui †,
Huang Bisheng †,
Zhuo Dong ,
Xu Yujie ,
Li Huitao ,
Zhan Xiangcheng ,
Ge Ren-Shan Email author and
Xu Yunfei Email author

†Contributed equally

BMC Pharmacology and Toxicology201920:32

https://doi.org/10.1186/s40360-019-0312-z

Received: 13 October 2018
Accepted: 9 May 2019
Published: 27 May 2019

Open Peer Review reports

Abstract

Background

It is an established fact that excess of glucocorticoids could cause the harmful effects, such as suppression on the male reproduction. Although glucocorticoids pharmacologically inhibit the Leydig cell function, their roles in Leydig cell development are unclear. Therefore, the present study was designed to investigate effects of synthetic glucocorticoid dexamethasone (DEX) on rat stem Leydig cell proliferation and differentiation.

Methods

Male Sprague-Dawley rats received a single intraperitoneal injection of 75 mg/kg EDS to eliminate Leydig cells and an in vitro culture system of the seminiferous tubules was established from Leydig cell-depleted testis. Using basal medium and Leydig cell differentiation-inducing medium (LIM) in the culture system, we examined the effects of DEX (0–100 nM) on the proliferation and differentiation of the stem Leydig cells in vitro, respectively.

Results

Results showed that LIM is a good agent to induce stem Leydig cell differentiation into Leydig cells that produce testosterone in vitro. DEX inhibited the differentiation of stem Leydig cells by reducing the expression levels of Cyp17a1 and Scarb1 and that NR3C1 antagonist RU38486 reversed the DEX-mediated effects. However, DEX are not involved with the proliferation of stem Leydig cells.

Conclusions

DEX suppressed the differentiation of rat Leydig cells in vitro and glucocorticoid-induced effects acted through NR3C1. This suppression partially targets on Cyp17a1 and Scarb1 gene expression.