Ciliary neurotrophic factor stimulates stem/progenitor Leydig cell proliferation but inhibits differentiation into its lineage in rats.

Abstract

Ciliary neurotrophic factor (CNTF) is a member of the interleukin-6 family of cytokines. CNTF drives many cells for their development. However, its effects on Leydig cells (LCs) development remains unclear. In the current study, we used 3D seminiferous tubule culture system to induce the proliferation and differentiation of tubule-associated stem Leydig cells (SLCs) and primary progenitor Leydig cells (PLCs) culture to address the effects of CNTF. We found that CNTF stimulated the proliferation of SLCs but inhibited its development to the LCs lineage. The CNTF-mediated effects can be reversed by STAT3 inhibitor S3I-201 and PI3K inhibitor wortmannin, indicating that CNTF acts via STAT3-PI3K signaling pathways to increase stem/progenitor Leydig cell proliferation. CNTF at 1 and 10 ng/mL significantly decreased androgen production by PLCs. Microarray analysis for CNTF-treated PLCs showed that CNTF blocked steroidogenic pathways through downregulating Scarb1, Star and Hsd3b1 possibly through the downregulating the transcription factor Nr5a1 expression. CNTF stimulates the proliferation but blocks the differentiation of stem/progenitor Leydig cells. This article is protected by copyright. All rights reserved.