Abstract
BackgroundIt 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.MethodsMale 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.ResultsResults 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.ConclusionsDEX 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.
Highlights
It is an established fact that excess of glucocorticoids could cause the harmful effects, such as suppression on the male reproduction
Leydig cell differentiation-inducing medium (LIM) can induce stem Leydig cell into the Leydig cell lineage To investigate the condition of in vitro differentiation of stem Leydig cells into the Leydig cell lineage, we cultured the seminiferous tubules in Basal medium (BM), or BM containing the following agents: ITS, luteinizing hormone (LH), LI, or ITS + LH + LI
This indicates that LIM is a good agent to induce stem Leydig cell differentiation into Leydig cells that produce testosterone in vitro
Summary
It is an established fact that excess of glucocorticoids could cause the harmful effects, such as suppression on the male reproduction. Glucocorticoids pharmacologically inhibit the Leydig cell function, their roles in Leydig cell development are unclear. The present study was designed to investigate effects of synthetic glucocorticoid dexamethasone (DEX) on rat stem Leydig cell proliferation and differentiation. Glucocorticoids play roles in many physiological functions [1]. NR3C1 is known to be a member of the nuclear steroid receptor superfamily and a ligand-dependent transcription factor that acts as a regulator in the expressions of glucocorticoid-responsive genes [2]. Glucocorticoids can suppress the male reproduction [1]. One of the targets by glucocorticoids is the Leydig cell in the testis. Leydig cells contain NR3C1 and glucocorticoids suppress
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