Mepartricin is a semi-synthetic
macrolide antibiotic developed as a
drug for the treatment of
benign prostatic hyperplasia (BPH) in human patients. In the present study, aged rats are used as an experimental model to evaluate the effects of
mepartricin on circulating
hormone concentrations and prostate receptor concentrations, to compare these possible effects with clinical findings observed in long-term treated dogs. Fifty-six aged male rats were randomly divided into four experimental groups treated orally with 0 (group 1), 2 mg (group 2), 5 mg (group 3) and 20 mg (group 4)
mepartricin/kg of
body weight. for 28 days respectively. Serum
oestradiol and
testosterone concentrations were measured by radio-immune-assays methods. Binding assays were used to measure the prostate concentrations of oestrogen receptors (ER),
androgen receptors (AnR), alpha(1)-adrenergic receptor (alpha(1)-AR), and beta-adrenerergic receptor (beta-AR) subtypes.
Mepartricin induced a significant reduction of prostate weight and serum
oestradiol concentrations. Serum
testosterone concentrations were unaffected. The treatment induced a significant down-regulation of ER concentrations (P < 0.05) and a significant up-regulation of AnR (P < 0.05) in rat prostate.
Mepartricin induced a significant (P < 0.05) dose-dependent up-regulation of alpha(1)-AR and beta(2)-AR. In contrast, the concentration of beta(3)-ARs was significantly decreased (P < 0.05) in treated animals. The increase in prostate beta(2)-AR concentrations observed in subjects treated with
mepartricin may be a favourable
element in the evolution of BPH, because of the role exerted by these receptors in the control of prostatic smooth muscle relaxation. Curiously, beta(3)-AR concentrations were significantly reduced in treated animals. Data collected suggest that the prostatic beta-AR expression might be strongly influenced by oestrogen deprivation (
mepartricin treatment); therefore, the combination of oestrogen suppression (
mepartricin) and
adrenergic suppression (alpha(1)-AR blockers) may be proposed as a possible nonhormonal therapeutic strategy for the treatment of
benign prostatic hyperplasia in dogs.