BACKGROUND: Men affected by liver cirrhosis frequently show clinical features of hypogonadism due to hormonal changes, in particular in the metabolism of 17beta-estradiol (E2) and testosterone (T). Sex hormone-binding globulin (SHBG), the major binding protein of these steroids in serum, is regularly elevated in such patients, with its androgen-binding properties possibly altered. In the present study, surface plasmon resonance biosensor techniques were used to determine whether the functional binding properties of this transporter are maintained in this pathology. METHODS: We selected 33 male patients with cirrhosis, Child-Pugh grade A or B, and 32 healthy males served as controls. Serum concentrations of T, E2, dehydroepiandrosterone sulfate (DHEAS) and SHBG were measured. In addition, ligand-binding properties of SHBG partially purified from sera of 23 cirrhotic patients and 20 controls were analyzed by a real-time biosensor technique using a surface-coated dihydrotestosterone derivative. RESULTS: The sensorgrams revealed that SHBG was fully bioactive in all samples investigated without any changes in binding kinetics. Moreover, total T concentrations were not significantly different in the cirrhotic patient sera (mean+/-SD 18.0+/-8.6 nmol/L) compared to controls (15.6+/-3.7; n.s.), whereas E2 was higher (152+/-60 vs. 96+/-29 pmol/L; p<0.0001) and DHEAS was lower (1493+/-1410 vs. 5099+/-2844 nmol/L; p<0.0001). CONCLUSIONS: Owing to elevated SHBG levels without changes in the steroid-binding properties in sera of cirrhotic male patients, free or bioavailable T concentrations are lower. This causes a shift of the hormonal balance in favor of E2, which exhibits a lower affinity for SHBG than androgens and accounts for the endocrine symptoms.
BACKGROUND:Men affected by liver cirrhosis frequently show clinical features of hypogonadism due to hormonal changes, in particular in the metabolism of 17beta-estradiol (E2) and testosterone (T). Sex hormone-binding globulin (SHBG), the major binding protein of these steroids in serum, is regularly elevated in such patients, with its androgen-binding properties possibly altered. In the present study, surface plasmon resonance biosensor techniques were used to determine whether the functional binding properties of this transporter are maintained in this pathology. METHODS: We selected 33 male patients with cirrhosis, Child-Pugh grade A or B, and 32 healthy males served as controls. Serum concentrations of T, E2, dehydroepiandrosterone sulfate (DHEAS) and SHBG were measured. In addition, ligand-binding properties of SHBG partially purified from sera of 23 cirrhotic patients and 20 controls were analyzed by a real-time biosensor technique using a surface-coated dihydrotestosterone derivative. RESULTS: The sensorgrams revealed that SHBG was fully bioactive in all samples investigated without any changes in binding kinetics. Moreover, total T concentrations were not significantly different in the cirrhotic patient sera (mean+/-SD 18.0+/-8.6 nmol/L) compared to controls (15.6+/-3.7; n.s.), whereas E2 was higher (152+/-60 vs. 96+/-29 pmol/L; p<0.0001) and DHEAS was lower (1493+/-1410 vs. 5099+/-2844 nmol/L; p<0.0001). CONCLUSIONS: Owing to elevated SHBG levels without changes in the steroid-binding properties in sera of cirrhotic male patients, free or bioavailable T concentrations are lower. This causes a shift of the hormonal balance in favor of E2, which exhibits a lower affinity for SHBG than androgens and accounts for the endocrine symptoms.
Authors: L L Bañez; R M Loftis; S J Freedland; J C Presti; W J Aronson; C L Amling; C J Kane; M K Terris Journal: Prostate Cancer Prostatic Dis Date: 2010-03-02 Impact factor: 5.554