Smooth muscle (SM) is a major component of the hyperplastic stroma in benign prostatic hyperplasia (BPH). In many muscle systems, muscle cell contractile protein and extracellular matrix (ECM) gene expression are modulated by alpha-adrenergic and androgenic signals. Given the known importance of androgens and sympathetic innervation in the pathophysiology of BPH, the potential role of these regulatory signals in the prostate is obvious. Unfortunately, the prostatic smooth muscle cell has been largely neglected in recent studies of prostate cell and molecular biology. We propose to characterize the expression of an important contractile protein in the prostatic smooth muscle cell, myosin heavy chain (MHC), and determine whether androgenic and alpha adrenergic signals regulate expression. In addition, prostatic ECM will be characterized at the protein biochemical level and similar regulatory issues studied. Protein biochemical, immunohistochemical, and molecular biologic techniques will be utilized to address the following specific aims; 1) Cloning of human smooth muscle MHC, 2) Development of monospecific antibodies for immunoblot and immunohistochemical analysis, 3) Characterization of MHC expression in the prostate, 4) Characterization of non-muscle MHC expression in the prostate, 5) Regulation of MHC and ECM expression in the human prostate by alpha- adrenergic and androgenic signals, and 6) Characterization and regulation of ECM expression. These studies should provide significant new insight into the role of the prostatic smooth muscle cell in the pathophysiology of BPH.
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