Glucagon-like peptide-1 receptor is expressed in human and rodent testis

Andrology. 2020 Nov;8(6):1935-1945. doi: 10.1111/andr.12871. Epub 2020 Aug 11.

Abstract

Background: The incretin hormone glucagon-like peptide-l (GLP-1) is an important regulator of post-prandial insulin secretion, acting through a G protein-coupled cell surface receptor (GLP-1R). In addition to its expression in pancreatic β-cells, several studies suggested that GLP-1R is located in extra-pancreatic tissues.

Objectives: In this study, we examined for the first time the testicular distribution of the GLP-1R, both in normal human and neoplastic testicular tissues as well as in rodent testis and rodent testicular cell lines.

Methods and methods: The GLP-1R distribution in testicular section has been evaluated by immunohistochemistry, the specificity of IHC was validated by demonstrating a positive staining for GLP-1RmRNA by RISH technology. While GLP-1R expression in terms of protein was detected by western blot analysis, Moreover, mRNA levels were determined in human testis, in rodent Leydig, and Sertoli cell lines.

Results: Using immunohistochemistrya specific staining for GLP-1R was detected in Leydig cells. The specificity of IHC was validated by demonstrating a positive staining for GLP-1RmRNA only in these cell types. Species differences in the GLP-1R expression between humans and rodents were observed. Interestingly, a decreased expression of the receptor in rodent tumor Leydig cell line and an absence in human Leydig tumor samples was detected.

Discussion: It may be hypothesized that GLP-1R acts like an oncosuppressor in Leydig tumors. A role in regulation of hormone secretion by GLP-1 has been shown in other endocrine cells, therefore we hypothesized that GLP-1R is able to modulate somehow the Leydig cell function.

Conclusion: In our findings, a careful evaluation of human testicular tissues and rodent testis revealed Leydig cells as a potential target for GLP-1. Collectively, an effect of GLP-1R in Leydig cell function may be presumed although future studies are needed to ascertain the GLP-1R's role both in normal and tumor Leydig cells.

Keywords: GLP‐1R; Leydig cells; Sertoli cells; pancreatic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Exenatide
  • Glucagon-Like Peptide-1 Receptor / metabolism*
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Testis / metabolism*

Substances

  • GLP1R protein, human
  • Glp1r protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Exenatide