Journal Article

Molecular Profile and Clinical Associations of Androgen Receptor Coactivators and Structural Genes in Benign Prostatic Hyperplasia and Metabolic Syndrome

Maluf, Feres Camargo, Guimarães, Vanessa, dos Santos, Gabriel A., Silva, Iran Amorim, Srougi, Miguel, Nahas, William, Reis, Sabrina, da Silva, Karina Serafim, Leite, Katia, Caetano, Giovana Vilas Boas, Brito, Pedro Henrique Souza, Candido, Patricia, Pimenta, Ruan, Antunes, Alberto Azoubel

2025

Overview

Background/Objectives: Benign prostatic hyperplasia (BPH) is a common condition in older men and represents a major contributor to lower urinary tract symptoms, prostate enlargement, and features of metabolic syndrome (MetS). Androgen receptor (AR) signaling and extracellular matrix (ECM) remodeling play central roles in BPH pathology, yet the clinical relevance of AR coactivators and structural genes remains incompletely understood. Methods: Prostate tissues from 76 BPH patients and five non-hyperplastic controls were analyzed by quantitative PCR to assess AR coactivators (SRC-1, SRC-2, SRC-3, PCAF, p300) and ECM-related genes (COL1A1, COL3A1). Results: BPH tissues showed marked overexpression of AR coactivators and collagen genes compared to controls (fold changes ≥ 7.8). Higher prostate-specific antigen (PSA) levels (≥10 ng/mL) and enlarged prostate volumes (≥100 mL) were associated with increased expression of PCAF, p300, SRC-1, and COL1A1. PSA and prostate volume correlated positively with triglycerides and VLDL, and inversely with HDL. Strong associations between collagen genes and p160 coactivators suggest coordinated androgenic and stromal remodeling activity. COL1A1 expression was reduced in patients under pharmacological treatment, particularly with alpha-blockers or combination therapies. PCAF and p300 were elevated in patients with MetS, hyperlipidemia, or hyperglycemia. Conclusions: These findings define a molecular signature in BPH linking androgenic, metabolic, and stromal pathology. SRC-1, PCAF, p300, and COL1A1 emerge as potential biomarkers and therapeutic targets, providing new insights into the molecular mechanisms of BPH progression.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: androgen coregulators / Androgen receptors / Androgens / Biopsy / Cholesterol / Collagen / Collagen (type I) / Drug therapy / Dutasteride / Epigenetics / Extracellular matrix / Gene expression / Genes / Health aspects / High density lipoprotein / Hyperglycemia / Hyperlipidemia / Hyperplasia / Hypertrophy / Lipoproteins (very low density) / Medical records / Medical screening / Metabolic syndrome / Molecular modelling / Pathology / Pathophysiology / Patient compliance / Patients / Prostate / Prostate cancer / Prostate-specific antigen / prostatic hyperplasia / Statistical analysis / Steroid receptor coactivator 1 / Therapeutic targets / Triglycerides / Urinary tract / Variance analysis