Terazosin treatment suppresses basic fibroblast growth factor expression in the rat ventral prostate

Abstract

Purpose: Alpha1-adrenergic receptor antagonists may not act solely on smooth muscle contractility. We evaluated the in vivo effect of the alpha1 blocker, terazosin, on the expression of basic fibroblast growth factor (bFGF) in the rat ventral prostate. Methods: Wistar rats were treated with terazosin (1.2 mg/ kg body weight, po, every second day) for 120 days. The expression of bFGF was assessed immuno-histochemically in tissue sections and by Western blotting in whole tissue preparations. Results: Terazosin treatment did not affect prostate weight or histomorphology. In the control group, epithelial and stromal cells demonstrated positive staining for the antibFGF antibody. In contrast, the same staining in terazosintreated specimens was either absent or extremely weak. An analogous difference was observed among the corresponding immunoblots. Conclusions: These findings implicate the reduction of bFGF expression by terazosin as a potential additional molecular mechanism of its action that may include alterations in peptide growth factor mediated prostate homeostasis.Drugs that block the action of sympathetic neurotransmitters on 1-adrenergic receptors ( 1-ADRs) are widely used for the treatment of patients with benign prostate hyperplasia (BPH)-related lower urinary tract symptoms. The rationale for their use stems is that they effectively relax prostate smooth muscles, 1 which represent approximately 40% of the cellular volume in hyperplastic glands. 2 The biological effects of extrinsic factors such as hormones and other endocrine-related agents on the prostate are mediated by various peptide growth factors produced by the gland and influence prostate growth, differentiation and function by promoting inter-and intracellular signaling between and within cell populations, through paracrine, autocrine and intracrine effects. 3 Data from several studies indicate that 1-ADR antagonists may not act solely on smooth muscle contractility. Intact autonomic innervation of the rat ventral prostate is necessary to maintain its structural and functional integrity. [4][5][6] Administration of the sympathomimetic phenylephrine induces ventral prostate hyperplasia associated with reduced rates of cellular apoptosis, but not with increased rates of cellular proliferation. 7 Moreover, rapid proliferation of prostatic epithelial cells has been seen in the spontaneously hypertensive rat, 8 an animal model with in-ORIGINAL RESEARCH

Age-related changes in the innervation of the prostate gland

“…In rats, the in vivo administration of non-selective α 1 -adrenoceptor antagonists results in a reduction in prostatic weight 102 as well as cellular proliferation 103 . This effect appears to be dose dependent, as low doses of α 1 -adrenoceptor antagonist have no effect on prostatic weight 104 . Our observations with knockout mice (Fig.…”

Combination of solifenacin with tamsulosin reduces prostate volume and vascularity as opposed to tamsulosin monotherapy in patients with benign prostate enlargement and overactive bladder symptoms: Results from a randomized pilot study

“…18 By contrast, the quinazoline-based ablockers (terazosin and doxazosin) were found to exert a potent apoptotic effect against prostate cancer cells through an a1-adrenoreceptor-independed pathway, caspace-3 and enhanced expression of transforming growth factor-b1. 18 By contrast, the quinazoline-based ablockers (terazosin and doxazosin) were found to exert a potent apoptotic effect against prostate cancer cells through an a1-adrenoreceptor-independed pathway, caspace-3 and enhanced expression of transforming growth factor-b1.…”

Terazosin Treatment Induces Caspase-3 Expression in the Rat Ventral Prostate

“…In previous studies we have showed that terazosin may also exert its apoptotic action through a differential effect on the glycosaminoglycans and matrix metalloproteinase 2 of the rat prostate extracellular matrix (ECM) [13], and by inducing a considerable decrease in basic fibroblast growth factor (bFGF) immunohistochemical expression [14]. ECM regulates, among others, the trafficking of growth factors, while bFGF is one of the main promoters of cellular proliferation inducing epithelial growth [15].…”