PDE7B is involved in nandrolone decanoate hydrolysis in liver cytosol and its transcription is up-regulated by androgens in HepG2.

Emmanuel Strahm,Lena Ekstrã¶M,Anders Rane

doi:10.3389/fphar.2014.00132

Emmanuel Strahm, Lena Ekstrã¶M + Show 1 more

Open Access

https://doi.org/10.3389/fphar.2014.00132

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Abstract

Most androgenic drugs are available as esters for a prolonged depot action. However, the enzymes involved in the hydrolysis of the esters have not been identified. There is one study indicating that PDE7B may be involved in the activation of testosterone enanthate. The aims are to identify the cellular compartments where the hydrolysis of testosterone enanthate and nandrolone decanoate occurs, and to investigate the involvement of PDE7B in the activation. We also determined if testosterone and nandrolone affect the expression of the PDE7B gene. The hydrolysis studies were performed in isolated human liver cytosolic and microsomal preparations with and without specific PDE7B inhibitor. The gene expression was studied in human hepatoma cells (HepG2) exposed to testosterone and nandrolone. We show that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate and nandrolone decanoate in liver cytosol. The gene expression of PDE7B was significantly induced 3- and 5- fold after 2 h exposure to 1 μM testosterone enanthate and nandrolone decanoate, respectively. These results show that PDE7B is involved in the activation of esterified nandrolone and testosterone and that the gene expression of PDE7B is induced by supra-physiological concentrations of androgenic drugs.

Highlights

Testosterone has been therapeutically used for several decades, primarily for androgen replacement therapy in hypogonadal men
INHIBITOR STUDIES In a previous study we showed that the hydrolysis of testosterone enanthate in human liver homogenates was inhibited by specific PDE7 inhibitor BRL50481
In order to evaluate if phosphodiesterase 7B (PDE7B) is involved in the hydrolysis of nandrolone decanoate, the specific PDE7B/PDE7A inhibitor BRL50481 was added to the incubation assay

Summary

Introduction

Testosterone has been therapeutically used for several decades, primarily for androgen replacement therapy in hypogonadal men These agents are commonly abused by athletes and sportsmen to improve muscle mass. The abuse of these compounds for cosmetic purposes among non-competing recreational body-builders and non-athletes is a major social concern and has become a growing health problem (Pope and Katz, 1994; Eklof et al, 2003; Sjoqvist et al, 2008; Kanayama et al, 2009). Most of the androgenic drugs are available as esters, e.g., testosterone enanthate, nandrolone decanoate, since the androgen itself undergoes first pass metabolism These drugs have a prolonged depot action due to slow release of the lipophilic steroid ester from the injection site. We have previously demonstrated that phosphodiesterase 7B (PDE7B) is involved in the hydrolysis and activation of testosterone enanthate (Ekstrom et al, 2011)

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