Nesfatin-1 regulates steroidogenesis in mouse Leydig cells

Area of Science:

• Reproductive Endocrinology
• Molecular Endocrinology
• Cell Biology

Background:

• Nesfatin-1, derived from nucleobindin 2 (NUCB2), is a polypeptide hormone involved in appetite and energy metabolism.
• Nesfatin-1 expression is observed in various peripheral tissues, including reproductive organs, but its testicular function is largely unknown.
• Leydig cells are crucial for testosterone production in the testis.

Purpose of the Study:

• To investigate the expression of NUCB2 mRNA and nesfatin-1 protein in mouse Leydig cells and TM3 cells.
• To determine the regulation of Nucb2 mRNA expression by gonadotropins.
• To examine the effect of exogenous nesfatin-1 on steroidogenesis in Leydig cells.

Main Methods:

• Quantification of Nucb2 mRNA and nesfatin-1 protein in primary Leydig cells and TM3 cells.
• Treatment with gonadotropins (pregnant mare's serum gonadotropin and human chorionic gonadotropin) to assess Nucb2 mRNA regulation.
• Assessment of steroidogenesis-related gene expression (Cyp17a1, Hsd3b) following nesfatin-1 treatment.

Main Results:

• Nucb2 mRNA and nesfatin-1 protein were detected in primary Leydig cells and TM3 cells, with evidence of nesfatin-1 binding sites.
• Gonadotropin treatment significantly increased Nucb2 mRNA expression in testicular tissues and Leydig cell models.
• Exogenous nesfatin-1 upregulated the expression of steroidogenic genes Cyp17a1 and Hsd3b in both primary Leydig cells and TM3 cells.

Conclusions:

• NUCB2/nesfatin-1 expression in mouse Leydig cells is potentially regulated by the hypothalamic-pituitary-gonadal axis.
• Nesfatin-1 produced within Leydig cells may exert autocrine control over steroidogenesis.
• These findings offer insights into Leydig cell NUCB2/nesfatin-1 regulation and its role in steroidogenesis, with potential implications for male reproductive health.