# Elevated luteinizing hormone receptor signaling or selenium treatment leads to comparable changes in adrenal cortex histology and androgen-AR/ZIP9 signaling

## TL;DR

This study shows that elevated LH receptor signaling or selenium treatment causes similar changes in adrenal cortex structure and androgen signaling in mice and rabbits.

## Contribution

The study introduces a novel comparison of LH receptor signaling and selenium effects on adrenal androgen signaling using transgenic mice and rabbit models.

## Key findings

- Both LH receptor signaling and selenium treatment caused adrenal cortex cell hypertrophy.
- AR expression decreased in both models, while ZIP9 expression varied depending on the model and selenium dose.
- Testosterone and zinc levels increased in mice but decreased in selenium-treated rabbits.

## Abstract

The importance and regulation of adrenal androgen production and signaling are not completely understood and are scarcely studied. In addition, there is still a search for appropriate animal models and experimental systems for the investigation of adrenal physiology and disease. Therefore, the main objective of the study was to evaluate the effect of luteinizing hormone (LH) signaling and selenium (Se2+) exposure on androgen adrenal signaling via canonical androgen receptor (AR), and membrane androgen receptor acting as zinc transporter (zinc- and iron-like protein 9; ZIP9). For herein evaluations, adrenals isolated from transgenic mice with elevated LH receptor signaling (KiLHRD582G) and adrenals obtained from rabbits used for ex vivo adenal cortex culture and exposure to Se2+ were utilized. Tissues were assessed for morphological, morphometric, and Western blot analyses and testosterone and zinc level measurements.

Comparison of adrenal cortex histology and morphometric analysis in KiLHRD582G mice and Se2+-treated rabbits revealed cell hypertrophy. No changes in the expression of proliferating cell nuclear antigen (PCNA) were found. In addition, AR expression was decreased (p < 0.001) in both KiLHRD582G mouse and Se2+-treated rabbit adrenal cortex while expression of ZIP9 showed diverse changes. Its expression was increased (P < 0.001) in KiLHRD582G mice and decreased (P < 0.001) in Se2+-treated rabbits but only at the dose 10 ug/100 mg/ tissue. Moreover, increased testosterone levels (P < 0.05) and zinc levels were detected in the adrenal cortex of KiLHRD582G mice whereas in rabbit adrenal cortex treated with Se2+, the effect was the opposite (P < 0.001).