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2.03.2017

New Study Sheds Light on Challenging Prostate Disease

Benign prostatic hyperplasia (BPH) leads to an enlargement of the prostate gland and affects the majority of men in their 60s. As the prostate grows, it can constrict the urethra, making it difficult to urinate, and cause other uncomfortable complications. Unfortunately, current treatments are not completely effective.

But a recent study by University of Miami Miller School of Medicine and Miami VA Medical Center researchers, led by Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c., the 1977 Nobel Prize winner for Physiology or Medicine, distinguished professor of pathology at the Miller School of Medicine, and a distinguished medical research scientist in the Department of Veterans Affairs, could lead to new, more-effective BPH therapies.

The study, published in the journal PNAS, was carried out by Petra Popovics, Ph.D., senior research associate in the Miller School Department of Medicine’s Division of Endocrinology, Diabetes and Metabolism, and first author on the paper, and Ferenc Rick, M.D., Ph.D., senior research scientist at the Miami VA Medical Center. The pair investigated a molecule called growth hormone-releasing hormone (GHRH). Secreted by the pituitary gland, GHRH normally stimulates growth hormone production, which produces another hormone (IGF1) that spurs cell growth.

The authors found, that the problem may arise when too much GHRH is released — not by the pituitary but by the prostate itself. Chronic inflammation encourages the prostate to secrete GHRH, which stimulates cell proliferation. This process could actually remodel the gland, changing the nature of prostate cells (a process called epithelial-to-mesenchymal transition or EMT) and driving fibrosis, a form of scarring that can also enlarge the gland and impair prostatic function.

“The inflammatory environment induced GHRH expression in both cultured cells and an experimental animal model of autoimmune prostatic inflammation,” said Popovics. “It’s likely that GHRH acts as a local growth factor under these circumstances.”

The researchers tried to disrupt this cycle by introducing a potential therapy with GHRH antagonists, MIA-690 and JV-I-38. They hoped that by blocking the connection between GHRH and its cellular receptor, they could prevent EMT and reduce tissue buildup.

“These GHRH antagonists bind to GHRH receptors with high affinity, blocking GHRH binding and decreasing its activity,” said Popovics. “MIA-690 inhibited inflammation-induced prostatic enlargement by 30 percent.”

This is the first time scientists have shown that GHRH antagonists can inhibit the cell proliferation associated with prostatic inflammation. The researchers believe these compounds currently being developed pre-clinically might eventually help patients with BPH. However, before that can happen, they must better understand the mechanisms that lead to increased GHRH secretion and BPH. The hope is that this class of compounds will be advanced to human clinical trials.

Schally added: “BPH is a major health problem for men over 60 years old, and development of new therapies is essential because present treatments are not efficacious. We have two classes of compounds that could be developed for treatment of this condition.”

“There is a growing body of evidence that chronic inflammation is a key factor in the development of BPH,” said Popovics. “We believe that GHRH antagonists could be clinically useful to treat early and advanced stages of BPH due to their anti-proliferative and anti-inflammatory activity.”

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