Benign prostatic hyperplasia and prostate-specific antigen

Abstract

Androgens and prostate functionTestosterone (T) and 5α-dihidrotestosterone (DHT) play a crucial role in the fetal prostate development. These androgens stimulate mesenchyme, while mesenchyme induces the proliferation of the epithelial buds from the urogenital sinus. This process, called "mesenchyme-epithelial interaction", starts in the 10th gestational week and continues in the adult age 1, 2 . Testosterone induces the development of the seminal vesicles and Wolffian ducts, while DHT induces the development of the prostate, penis and scrotum.Prostatic tissue is composed of stroma and epithelium. Prostatic stroma is composed of stromal cells (fibroblasts, endothelial capillary cells, lymph vessels and smooth muscle cells), neuroendocrine (NE) cells, neural cell axons, intercellular liquid and collagen fibers 3 . Prostatic epithelium is composed of secretory, basal, intermediary and NE cells. Secretory cells synthesize and secrete various proteins, like prostate specific antigen (PSA), prostatic acid phosphatase (PAP), androgen receptor (AR) and make the greatest part of the prostatic epithelium. It is believed that NE cells induce growth, differentiation, and secretory functions of the prostatic epithelium 4 .Numerous factors regulate prostatic growth: endocrine, neuroendocrine, paracrine, or growth factors (GF), autocrine and intracrine factors. However, the action of the endocrine factors is the best known. Testosterone is the most important serum androgen in the male, with the average serum concentration of 611 ± 186 ng/dL, while the average DHT serum concentration is 56 ± 20 ng/dL. However, the average concentration of active, free T is only 12.1 ± 3.7 ng/dL, while the rest is bound to the globulins and albumins. The major androgen in the prostatic tissue is DHT, with the average tissue concentration of 2.4-5.1 ng/g. The average tissue concentration of T is 3-5 times lower and measures 0.9 ng/g 5-7 .Only free T molecules can enter the prostatic cell, by diffusion. In the cytosol, one part of T molecules transforms into DHT. Both T and DHT bind to AR and form androgen-AR complexes. Subsequently, those complexes make pairs, entering the nucleus and bind to androgen-responsive elements (ARE) on DNA. After the information was transcripted from DNA to mRNA, mRNA leaves the nucleus and comes on ribosomes, where the information is translated into protein. Enzyme 5-alpha reductase (5αR) performs the conversion of T to DHT. There are two isoforms of 5αR: type 5αR-2 is dominant in the prostatic stroma and accessory genital tissues. Type 5αR-1 is present in the skin and prostate epithelium. Benign prostate hyperplasiaBenign prostate hyperplasia (BPH) denotes progressive prostatic enlargement, associated with the symptoms of impaired emptying of the urinary bladder and followed with gradual progression of the symptoms and complications. The most common BPH-related complications are chronic urinary infection, urinary bladder stones, chronic and acute urinary retention. The prevalence of BPH is very high: BPH is the fourth...

Longitudinal changes in prostate volume in a community‐based cohort study of middle‐aged and elderly men in rural China

“…PSA is used as a tumor marker for prostate cancer screening and diagnosis, and it will increase with benign prostatic hyperplasia (Pejcic et al , ). Our finding matches those observed in earlier studies that serum PSA was highly correlated with prostate size (Park et al , ; Park et al , ).…”

“…Although steroid hormones are among the most common factors that induce the development of BPH (Pejcic et al , ), testosterone is considered not directly involved in the hyperplasia (Carson & Rittmaster, ). The dihydrotestosterone (DHT), converted from testosterone by 5‐alpha‐reductase enzymes in prostate, is a more potent stimulator of prostate growth (Carson & Rittmaster, ).…”

“…The dihydrotestosterone (DHT), converted from testosterone by 5‐alpha‐reductase enzymes in prostate, is a more potent stimulator of prostate growth (Carson & Rittmaster, ). The gradual decrease of testosterone concentration is characteristic for an aging man; however, DHT concentration increases in prostatic tissue, or remains unchanged (Pejcic et al , ). But intra‐prostatic tissue DHT levels had no correlation with peripheral serum DHT concentrations, nor did prostate weight (Olsson et al , ).…”

Genetic association between PSA-158G/A polymorphism and the susceptibility of benign prostatic hyperplasia: a meta-analysis

“…Prostate specific antigen (PSA) is a glucoproteinase, and its active form is a serine protease composed by 237 residues [ 8 ]. 70% of PSA have chymotrypsin-like activity, and are closely related to male fertility [ 9 ].…”