IGF-1 as selected growth factor multi-response to antidepressant-like substances activity in C57BL/6J mouse testis model

Abstract

Insulin-like growth factor (IGF-1) affects almost all cells in the body. Extremely important functions of this growth factor have been demonstrated in the brain and the reproductive system of both, females and males. Also, it is considered as a pro-inflammatory cytokine adjusting tissue homeostasis. However, it seems to play a special role in the male reproductive system and it may be disturbed by the application of antidepressants with different mechanisms of drug action during therapy. To date, the effect of antidepressant-like substances (ALS) on the course of physiological processes in male testicular cells is poorly understood. Therefore, the purpose of the research was to determine the presence, localizationof IGF-1R (insulin-like growth factor 1 β receptor) and mRNA gene expression of IGF-1R and IGF-1 after administration of 3-[(2-methyl-1,3-tiazol-4-yl)ethynyl]-pyridine (MTEP) and N-[2-(Cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) in the different scheme in the testis of mice. Imipramine was used as a reference drug having a documented interaction with the mGluR5 receptors. The immunohistochemical analyses showed the localization of IGF-1R in Sertoli, Leydig, and germinal cells after all used substances. Differences in receptor localization were observed depending on the drugs applied and the type of analyzed cells. In contrast, there was a significant increase in IGF-1 gene expression after IMI + NS-398 and in IGF-1R after MTEP + NS-398 and IMI + NS-398 administration. It can, therefore, be assumed that the use of a combination of NS-398 with some ALS may run different mechanisms of action and affect the regulation of reproductive function in mouse testis through maintaining homeostasis at the molecular and immunological levels related to IGF.

Keywords: IGF-1; IGF-1R; antidepressant-like substances; reproduction; testis.