Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome

Abstract

The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS.

TRPM8 contributes to sex dimorphism by promoting recovery of normal sensitivity in a mouse model of chronic migraine

“…Testosterone (T1500, Merck) was dissolved in 45% 2-Hydroxypropyl-β-cyclodextrin in water 84 to obtain a solution of 22 mg/ml for sustained delivery. This solution or its vehicle was introduced inside Alzet osmotic minipumps (Model 2004, Durect Corporation, Cupertino, CA, USA) to achieve a testosterone delivery of 6 μg/h, based on previous studies obtaining significant effects in orchidectomized mice 29 , 85 .…”

A Chemoenzymatic Strategy for the Synthesis of Steroid Drugs Enabled by P450 Monooxygenase-Mediated Steroidal Core Modification

“…17β-Hydroxyestra-4,9,11-trien-3-one (Trenbolone ( 3 ), Figure ), as a synthetic analog of testosterone, is a potent anabolic–androgenic steroid and can be used as a selective androgen receptor modulator in the treatment of obesity and androgen insensitivity syndromes in humans . This special physiological activity has been attributed mainly to the presence of a double bond between carbons 11 and 12, which slows down the metabolism of 3 , greatly increases its binding affinity to the androgen receptor, and inhibits it from aromatizing .…”

Testosterone Deprivation Aggravates Left-Ventricular Dysfunction in Male Obese Insulin-Resistant Rats via Impairing Cardiac Mitochondrial Function and Dynamics Proteins

“…A recent study showed that obese insulin-resistant rats subjected to testos terone deprivation in middle age had an exacerbated insulin-resistant condition as indicated by increased HOMA-IR [12]. In addition, LV mass was also reduced and serum CK-MB levels were increased in testosterone-deprived obese insulin-resistant rats subjected to myocardial ischemia reperfusion injury [13]. Currently, the process involved in the alteration of cardiometabolic function in testosterone-deprived obese insulin-resistant rats remains unknown.…”