Knockdown of type 2 orexin receptor in adult mouse testis potentiates testosterone production and germ cell proliferation

IF 3.8 3区医学 Q2 CELL BIOLOGY Molecular and Cellular Endocrinology Pub Date : 2024-06-10 DOI:10.1016/j.mce.2024.112312

Pratikshya Sahoo , Debarshi Sarkar , Shubhangi Sharma , Arpit Verma , Suraj Kumar Naik , Vikash Prashar , Jyoti Parkash , Shio Kumar Singh

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Abstract

Orexins (OXs) are neuropeptides which regulate various physiological processes. OXs exist in two different forms, mainly orexin A (OXA) and orexin B (OXB) and their effects are mediated via OX1R and OX2R. Presence of OXB and OX2R in mouse testis is also reported. However, the role of OXB/OX2R in the male gonad remains unexplored. Herein we investigated the role of OXB/OX2R system in testicular physiology under in vivo and ex vivo conditions. Adult mice were given a single dose of bilateral intratesticular injection of siRNA targeting OX2R and were sacrificed 96 h post-injection. OX2R-knockdown potentiated serum and intratesticular testosterone levels with up-regulation in the expressions of major steroidogenic proteins. Germ cell proliferation also increased in siRNA-treated mice. Results of the ex vivo experiment also supported the findings of the in vivo study. In conclusion, OX2R may regulate testosterone production and thereby control the fine-tuning between steroidogenesis and germ cell dynamics.

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敲除成年小鼠睾丸中的 2 型奥曲肽受体可促进睾酮生成和生殖细胞增殖。

奥曲肽是一种神经肽，可调节各种生理过程。OXs 以两种不同的形式存在，主要是 OXin A（OXA）和 OXin B（OXB），其作用通过 OX1R 和 OX2R 介导。也有报道称小鼠睾丸中存在 OXB 和 OX2R。然而，OXB/OX2R在雄性性腺中的作用仍未得到探索。在此，我们研究了体内和体外条件下 OXB/OX2R 系统在睾丸生理中的作用。成年小鼠接受单剂量双侧睾丸内注射靶向 OX2R 的 siRNA，注射后 96 小时处死。OX2R敲除可提高血清和睾丸内睾酮水平，并上调主要类固醇生成蛋白的表达。经 siRNA 处理的小鼠生殖细胞增殖也有所增加。体内外实验的结果也支持了体内研究的发现。总之，OX2R 可调节睾酮的产生，从而控制类固醇生成和生殖细胞动态之间的微调。

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来源期刊

Molecular and Cellular Endocrinology 医学-内分泌学与代谢

CiteScore

9.00

自引率

2.40%

发文量

174

审稿时长

42 days

期刊介绍： Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.