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Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies

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Testosterone recovery therapy targeting dysfunctional Leydig cells.

Samuel Garza¹, Vassilios Papadopoulos¹

¹Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.

|September 27, 2022

Summary

Low testosterone affects millions of men, impacting health and quality of life. New biologic therapies aim to boost natural testosterone production by targeting Leydig cells, offering alternatives to traditional hormone replacement.

Keywords:

aging hypogonadism infertility testis testosterone deficiency

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Area of Science:

Endocrinology
Molecular Biology
Reproductive Medicine

Background:

Reduced serum testosterone is a widespread condition linked to comorbidities and reduced quality of life.
Current testosterone replacement therapy has limitations and potential adverse effects, necessitating alternative treatments.
Testosterone biosynthesis occurs in testicular Leydig cells, involving complex protein interactions and a rate-limiting mitochondrial step.

Purpose of the Study:

To explore novel therapeutic strategies for increasing endogenous testosterone production.
To identify specific targets within Leydig cells for enhancing steroidogenesis.
To evaluate advanced biologics as potential treatments for testosterone deficiency.

Main Methods:

Investigated mechanisms of testosterone synthesis in testicular Leydig cells.
Examined endogenous targets regulating cholesterol translocation and steroidogenesis.
Reviewed the development of first-in-class biologics, including voltage-dependent anion channel peptides and cell transplantation.

Main Results:

Identified numerous endogenous targets within Leydig cells that can increase testosterone biosynthesis.
Demonstrated that enhancing steroidogenesis in Leydig cells is a viable therapeutic approach.
Highlighted novel biologic strategies that specifically target endogenous steroid formation.

Conclusions:

Novel biologic therapies offer promising avenues for enhancing endogenous testosterone formation.
Targeting Leydig cell steroidogenesis presents a specific strategy for treating testosterone deficiency.
Advanced approaches like VDAC peptides and cell transplantation may overcome limitations of current therapies.