Local growth hormone promotes benign prostatic hyperplasia

Area of Science:

• Endocrinology
• Urology
• Molecular Biology

Background:

• Nonpituitary growth hormone (npGH) and its receptor (GHR) are present in the prostate, and their expression correlates with age-related benign prostatic hyperplasia (BPH).
• Aging is associated with increased prevalence of BPH and potentially altered local hormone signaling within the prostate.

Purpose of the Study:

• To investigate the role of local prostate growth hormone (GH) action in the pathogenesis of benign prostatic hyperplasia (BPH).
• To determine if local GH signaling contributes to DNA damage and epithelial-mesenchymal transition (EMT) in the aging prostate.

Main Methods:

• Analysis of npGH, DNA damage marker (γH2AX), and EMT markers in human prostate tissues from different age groups and BPH specimens.
• In vitro studies using human primary prostate epithelial cells and BPH-derived cells treated with GH.
• In vivo studies in mice involving allografted GH-expressing fibroblasts and examination of adjacent prostate tissue.
• Assessment of cellular proliferation (Ki67), motility, and expression of EMT markers (TWIST2, E-cadherin).

Main Results:

• Human prostate tissue showed a >10-fold increase in npGH expression after age 60, coinciding with elevated DNA damage and EMT activation.
• GH treatment of prostate cells induced DNA damage, activated EMT (increased TWIST2, decreased E-cadherin), and enhanced proliferation and motility.
• In mice, prostate tissue near GH-expressing cells exhibited increased DNA damage, EMT markers, proliferation, and BPH-like morphological changes.
• GH induced DNA damage independently of IGF-1, although both promoted EMT.

Conclusions:

• Local npGH signaling in aging prostate tissue promotes DNA damage and EMT, creating a microenvironment conducive to BPH development.
• Prostate GHR signaling represents a potential therapeutic target for managing BPH.