Daidzein effects on ACTH cells: immunohistomorphometric and hormonal study in an animal model of the andropause.

Daidzein is a potential natural alternative to estradiol during therapy of some malignancies in men. Besides weak inhibition of tyrosine kinase activity, daidzein has a sizeable inhibitory effect on calcium channels. The aim of this study was to examine the effects of daidzein on the immunohistomorphometric features of pituitary adrenocorticotropes (ACTH cells) and circulating levels of ACTH and corticosterone, in comparison with estradiol, in an animal model of the andropause. Sixteen-month-old Wistar rats were divided into sham operated (SO), orchidectomized (Orx), estradiol treated orchidectomized (Orx+E) and daidzein treated orchidectomized (Orx+D) groups. Estradiol (0.625 mg/kg/day) and daidzein (30 mg/kg/day) were administered subcutaneously for three weeks, while the SO and Orx groups received the vehicle alone. ACTH cells were identified by the peroxidase-antiperoxidase (PAP) immunohistochemical procedure. Peripheral circulating concentrations of ACTH and corticosterone were measured by immunoassay. Orchidectomy reduced (p<0.05) the cell volume and volume density of adrenocorticotropes by 11% and 16%, respectively, in comparison to SO rats. In Orx+E rats, the volume density of ACTH cells decreased (p<0.05) by 25%, but the circulating level of ACTH increased (p<0.05) by 29%, compared to Orx rats. Daidzein treatment significantly decreased (p<0.05): volume density of ACTH cells, circulating ACTH and corticosterone by 24%, 48% and 33%, respectively, compared to the Orx group. In conclusion, this study revealed that daidzein negatively modulated the immunohistomorphometric features of ACTH cells and, unlike estradiol, decreased ACTH and corticosterone secretion, in an animal model of the andropause.

[Beta-adrenergic blockers in congestive heart failure: pro et contra?]. / Beta-adrenergicki blokatori u zastojnoj insuficijenciji srca: za ili protiv?

In every patient with congestive heart failure there is a secondary neurohumoral response including increase in serum noradrenaline, renin, angiotensin, aldosteron and antidiuretic hormone or arginine-vasopressin values. Plasma and urine noradrenaline levels are increased proportionally to the severity of ventricular dysfunction, but its reserve is often reduced in the myocardium as well as the density of beta receptors and sensitivity to catecholamines and inotropic responses to the stimulation of adrenergic nerves. Down-regulation of beta-adrenoceptors in the myocardium, verified by the technique of radioligands, with the reduced number of beta-adrenoceptors, is accompanied by the appearance of refractoriness and desensitization to endogenous and exogenous catecholamines. Chronic beta-blockade may improve haemodynamic and clinical function in patients with dilated cardiomyopathy or congestive heart failure, because beta-blockers have potentially beneficial actions: protection of the myocardium from damage by chronic excessive catecholamine stimulation, restoration toward normal of the down-regulated membrane beta-receptor density often seen in heart failure, reduction in the risk of potentially lethal ventricular arrhythmias and beneficial effects on substrate utilization. Our results of investigation in 20 patients with congestive heart failure treated with beta-blockers short and long-term (average 22 months) gave substantial increases in ejection cardiac index and improved functional class and also improved working capacity.