Testicular Translocator Protein Expression is Differentially Altered by Synthetic Cannabinoid HU210 in Adult and Adolescent Rats

Ronald Ho Yeung Chan

doi:10.4172/2155-6105.1000198

Abstract

Objective: The translocator protein (TSPO) has been implicated in numerous functions including steroid production and regulation of stress and anxiety. Cannabinoids have been shown to reduce plasma testosterone levels and alter anxiety levels. The aim of the present study was to determine whether the synthetic cannabinoid HU210 is able to regulate TSPO expression in several peripheral organs. Methods: HU210 (100 μg/kg) was administered intraperitoneally to both adult and adolescent male ratsfor 14 days. TSPO receptor expression in several organs, including the liver, spleen, kidneys and testes, was quantified by membrane receptor binding using the selective radiolig and, PK11195. In cases where receptor binding data indicated significant cannabinoid-induced differences, further RT-qPCR was carried out to determine the transcriptional regulation of the TSPO gene. Additionally, film-autography was used to identify potential changes in the spatial distribution of the TSPO tissue binding sites. Results: Results indicate that HU210 induces significant reductions in testicular TSPO expression in adult but not adolescent rats. No changes were found in other organs examined. These results are consistent with the previously observed effects of cannabinoids on testosterone production and a presumed role for TSPO in steroidogenesis. Conclusions: Overall, these results suggest that cannabinoids may alter testosterone production by altering the expression of testicular TSPO and that the alteration of TSPO occurs in an age-dependent manner.

Highlights

translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is a membrane bound protein found mainly on the outer mitochondrial membrane [1]
Given the role of TSPO in steroidogenesis, and stress and anxiety regulation, we examined the effect of a high-dose chronic administration of HU210, a non-specific cannabinoid receptor agonist, on TSPO expression
Multiple comparisons with Bonferonni correction found no significant differences in adult or adolescent groups which were to receive either HU210 or vehicle treatment prior to drug administration (p > 0.05 for all time points prior to HU210 or vehicle administration; Figure 1)

Summary

Introduction

TSPO, previously known as the peripheral benzodiazepine receptor, is a membrane bound protein found mainly on the outer mitochondrial membrane [1]. As TSPO is important to the production of steroids, it has been suggested to play a role in stress and anxiety regulation through the regulation of neurosteroids [20,21,22]. Neurosteroids such as allopregnanolone and dehydroepiandrosterone have been shown to modulate GABAA receptors and affect stress and anxiety responses [23,24,25,26]. The connection between TSPO and stress has been demonstrated in human and animal studies which have found a reversible down regulation of TSPO expression in the blood and peripheral organs in response to chronic stress or anxiety [6]

Methods

Results

Conclusion