Endocrine Abstracts

Introduction: 11β-HSD1 is the key enzyme of intracellular glucocorticoid regulation by converting inactive cortisone to active cortisol. The latter binds to the glucocorticoid and mineralocorticoid receptor (MR) in the heart. Cortisol excess in Cushing’s syndrome leads to left ventricular hypertrophy. Also androgens cause myocardial remodelling. However, the impact of testosterone on the cardiovascular system is strongly disputed showing beneficial and deleterious effects on cardiovascular disease factors. We investigated the effect of testosterone on 11β-HSD1 in the rat heart.

Methods: Male Wistar rats aged 8–10 weeks were orchiectomized and put on a low-salt (chow 0.03% NaCl+tap water) or high-salt diet (chow 4% NaCl+drinking water 0.09% NaCl) over 5 weeks. In addition, they received either placebo, testosterone (1 mg/animal) or 5alpha-dihydrotestosterone (DHT) (1 mg/animal) as daily s.c. injection over 16 days. In further experiments other rats were treated with the MR antagonist spironolactone (50 mg/kg weight per day), or the androgen receptor antagonist flutamide (30 mg/kg weight per day), or amiloride (1 mg/kg weight per day) additionally to testosterone or DHT. After decapitation cardiac 11β-HSD1 expression was assessed by real-time PCR.

Results: Testosterone significantly upregulated 11β-HSD-1 mRNA expression in the heart of salt-depleted orchiectomized rats. DHT showed the same trend, but did not reach significance. Pretreatment with spironolactone or flutamide completely abolished this testosterone effect, but not the pretreatment with amiloride. In addition, spironolactone significantly lowered cardiac 11β-HSD1 expression in high-salt compared to low-salt groups.

Conclusions: We suggest that testosterone increases intracardiac cortisol/corticosterone concentrations by enhancing 11β-HSD1 expression. This might contribute to left ventricular concentric remodeling as seen in Cushing’s disease and in patients with androgen abuse.