Benign prostatic hyperplasia (BPH) refers to a form of benign tumor commonly appearing in males during aging. It is characterized by an overproliferation of epithelial (lining) and stromal (structural support) cells of the prostate. Subsequent compression of the urethra can be accompanied by reduced urine outflow and decreased ability to empty the bladder. Some evidence suggests that prostate cell proliferation could be stimulated by precursors of neurotrophins (proneurotrpohins) through cellular signaling of membrane-bound receptor p75NTR. On the other hand, the role of testosterone on cell proliferation is controversial as depending on the physiologic context and age, it may promotes or reduces prostatic cell division. We here examine the relation between proneurotrophin and testosterone in vitro on cell cultures of normal rat prostatic cells in vitro.

Prostate tissue of Sprague-Dawley rats (10 weeks) was minced and digested with collagenase type II. Epithelial and stromal cells were seeded separately and incubated with either testosterone (500 nM), the p75NTR antagonist THX-B (50 µg/mL) or proneurotrophins nerve growth factor (proNGF) or brain-derived growth factor (proBDNF) (10 ng/mL). Neurotrophin secretion was measured by ELISA kits. Cell proliferation was examined by light and confocal microscopy.

Epithelial and stromal cells were characterized by microscopy using respectively pancytokeratin (AE1/AE3) and smooth muscle cell myosin antibodies. Incubation of epithelial and stromal cells with testosterone or THX-B for 48 hours decreased the secretion of proBDNF while BDNF, NGF and proNGF were unaffected. When looking at cell proliferation, addition of proBDNF or proNGF (10 ng/mL) increased epithelial and stromal cell growth. This effect was annihilated by preincubating cells with either testosterone (500 nM) or THX-B (50 µg/mL). Increase in cell mitosis by proneurotrophins was confirmed  by the increased number of cells positive for protein Ki67, a marker of mitosis. On the other hand, proneurotrophins triggered translocation of NFkB into the nucleus, which was partially prevented by THX-B but not by testosterone, suggesting different pathways used by testosterone and THX-B.

Testosterone slows down epithelial and stromal cell proliferation in vitro, at least in part, by decreasing the secretion of proneurotrophin proBDNF. Inhibition of p75NTR by THX-B confirmed the essential role of this receptor in prostatic cell growth.

These preliminary data suggest that clinical use of p75NTR antagonist such as THX-B could help limit prostatic cell proliferation in patients with BPH.

Continence 19S (2026) 102588
DOI: 10.1016/j.cont.2026.102588