Effect of ghrelin receptor ligands on proliferation of prostate stromal cells and on smooth muscle contraction in the human prostate
Abstract
Objectives: To study effects of the metabolic hormone ghrelin on prostate enlargement, stromal cell growth, and smooth muscle contraction, which are important factors in the pathophysiology of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). In fact, relationships between metabolic syndrome and BPH/LUTS were proven by epidemiologic studies, but underlying molecular mechanisms are largely unknown. Materials and methods: Effect of ghrelin and ghrelin receptor (GHSR) agonists were studied in isolated human prostate tissues and cultured stromal cells. Results: Ghrelin increased proliferation and viability of prostate stromal cells. RT-PCR identified several ghrelin-upregulated mRNAs, with possible roles in growth, cell cycle, or metabolism. In human prostate tissues, the effect of ghrelin inverse agonist PF-05190457 on the smooth muscle contraction was examed by an organ bath. In cultured stromal cells, ghrelin agonist MK0677 induced proliferation of stromal cells, shown by EdU assay, colony formation, flow cytometry, and viability. In myographic measurements, GHSR inverse agonist enhanced contractions of human prostate strips. Conclusions: Ghrelin system aggravates stromal cell growth and prostate smooth muscle contraction in BPH. Ghrelin may deteriorate urethral obstruction independently from BPH, qualifying the ghrelin system as an attractive new target to be tested for LUTS treatment in BPH.
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