Researchers still don’t fully understand how lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) arise. So, for a study, researchers sought to identify the mechanisms leading to the failure of BPH/LUTS medicinal treatment.

Individuals who failed medical treatment for BPH/LUTS and control patients had their levels of cholesterol and steroids in the transitional zone tissue measured. In addition, BPH cells were employed in organoid culture to explore prostatic branching, and qPCR was performed to evaluate the expression of the prostatic gene.

Low tissue DHT levels, elevated levels of steroid 5-α-reductase type II (SRD5A2), and decreased levels of androgen receptor (AR) target genes, prostate-specific antigen (PSA), and transmembrane serine protease 2 (TMPRSS2) were seen in BPH patients using a 5-α-reductase inhibitor (5ARI). Alpha-adrenergic receptor antagonists (α-blockers) did not increase the glucocorticoids (GC) levels in the prostatic tissue like 5ARI did. In the prostatic epithelium and stroma of all patient samples, GR was shown to be nuclear localized. Dexamethasone, a synthetic GC, caused budding and branching in 4 BPH organoid cell lines.

A 5ARI-induced route raised tissue levels of GC not found in individuals using α-blockers, although the medical treatment for BPH/LUTS remained to suppress androgenesis after failure. The stimulation of organoids by GC suggested that the GC receptors were a trigger for regulating prostate gland development. It was shown that GC activation could operate as a master regulator of prostatic branching and development through a 5ARI-induced route.