Melatonin Up-regulates the Expression of the GATA-4 Transcription Factor and Increases Testosterone Secretion from Leydig Cells Through RORα Signaling in an Goat Spermatogonial Stem Cell Differentiation Culture System

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jan 5

PMID 29299171

Citations 13

Authors

Shou-Long Deng

Yan Zhang

Kun Yu

Xiu-Xia Wang

Su-Ren Chen

De-Ping Han

C Yan Cheng

Zheng-Xing Lian

Yi-Xun Liu

Affiliations

Soon will be listed here.

Abstract

Because androgen function is regulated by its receptors, androgen-androgen receptor signaling is crucial for regulating spermatogenesis. Androgen is mainly testosterone secreted by testis. Based on the results of early studies in goats, the administration of melatonin over an extended period of time increases steroid production, but the underlying mechanism remains unclear. Here, we report the expression of the melatonin membrane receptors MT1 and MT2 and the retinoic acid receptor-related orphan receptor-alpha (RORα) in the goat testis. An differentiation system using spermatogonial stem cells (SSCs) cultured in the presence of testicular somatic cells was able to support the formation of sperm-like cells with a single flagellum. The addition of 10 M melatonin to the culture system increased RORα expression and considerably improved the efficiency of haploid cell differentiation, and the addition of the RORα agonist CGP52608 significantly increased the testosterone concentration and expression of GATA binding factor 4 (GATA-4). Furthermore, inhibitors of melatonin membrane receptors and a RORα antagonist (T0901317) also led to a considerable reduction in the efficiency of haploid spermatid formation, which was coupled with the suppression of GATA-4 expression. Based on these results, RORα may play a crucial role in enhancing melatonin-regulated GATA-4 transcription and steroid hormone synthesis in the goat spermatogonial stem cell differentiation culture system.

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