New Targets for Increasing Endogenous Testosterone Production

[Michael Scally MD]

Le B, Chen H, Zirkin B, Burnett A. New targets for increasing endogenous testosterone production: clinical implications and review of the literature. Andrology. New targets for increasing endogenous testosterone production: clinical implications and review of the literature - Le - 2014 - Andrology - Wiley Online Library

Over the past several decades, our understanding of the regulatory mechanisms of testosterone production has increased significantly. Concurrently, the medical treatment of hypogonadism, particularly in the ageing male has increased.

This review article consolidates some of our insights into the regulatory mechanisms of endogenous testosterone production and examines promising new targets that may allow endogenous production of testosterone to be re-established in males with primary hypogonadism.

We examined the published scientific literature regarding regulatory mechanisms of testosterone biosynthesis with a focus on Leydig cell physiology and small-molecule regulation that resulted in increased testosterone production.

We identified several pathways that have been manipulated pharmacologically to increase Leydig cell testosterone production, including phosphodiesterases, the cholesterol translocator protein, the electron transport chain of mitochondria, cyclooxygenases and osteocalcin.

Manipulation of these pathways with small molecules has helped further our understanding of the regulatory pathways of testosterone biosynthesis. Herein, we identified five future targets that might promote increased endogenous testosterone production through the Leydig cell instead of relying on exogenous testosterone administration.

 

[Michael Scally MD]

Signalling Pathways Involved in Leydig Cell Steroidogenesis and Potential Targets for Enhancing Testosterone Production

Currently, pharmacologic treatments for hypogonadism are limited to those that act through the LH receptor, such as hCG, clomiphene, or aromatase inhibitors, or by bypassing endogenous production entirely through the exogenous administration of testosterone.

Herein, we identified five future targets [In Bold: Phosphodiesterases; Translocator protein; Electron transport chain of mitochondria; Cox-2 and thromboxane A synthase; Osteocalcin] that might promote increased endogenous testosterone production through the Leydig cell instead of relying on exogenous testosterone administration. The common feature of each is that they do not rely upon the LH receptor.

The potential approaches use small molecules, dietary supplements, or even FDA-approved medications. Although the data for these pharmacologic agents come primarily from animal studies, further study in human trials could prove promising and deserve further study.

Legend: ATP, Adenosine Triphosphate; cAMP, Cyclic Adenosine Monophosphate; CBP, CREB Binding Protein; CREB, cAMP Response Element-Binding Protein;

COX-2, Cyclooxygenase 2; COX2i, Cyclooxygenase 2 inhibitor; GATA-4, Transcription Factor GATA4; GPRC6A, G-protein-coupled receptor encoded by GPRC6A;

hCG, Human Chorionic Gonadotropin; LH, Luteinizing Hormone; LH-R, LH Receptor; PKA, Protein Kinase A; PKAc, Protein Kinase A Catalytic subunit; SF-1,

Steroidogenic Factor 1; stAR, Steroidogenic Acute Regulatory Protein; TBXAS inhibitor, Thromboxane A Synthase inhibitor; TSPO, Translocator Protein.

 

[Transhuman]

does this suggest an experimental super-pct protocol? phosphodiesterase? does this mean viagra or cialis should be could be useful? i suppose the authors are considering drug methods for these too.. Translocator protein; Electron transport chain of mitochondria; Cox-2 and thromboxane A synthase; Osteocalcin. i remember reading on meso that adding hgh during pct could helpful. traditional nolva+clomid pct is good enough for me but must admit i'm curious about the perfect pct

 

[johsoed]

In primary hypogonadism there is a failure of testosterone production due to testicular failure. If the Leydig cells are already damaged or the declined, I think that is impossible to increase the endogenous testosterone production through the Leydig cells.