UM Nobel Laureate Collaborates on Study of Growth Hormone-Releasing Hormone
A team of international researchers, including Nobel laureate Andrew V. Schally, Ph.D., M.D.h.c., D.Sc.h.c., distinguished professor of pathology at the University of Miami Miller School of Medicine and distinguished medical research scientist in the Department of Veterans Affairs, has uncovered a surprising new activity of growth hormone-releasing hormone (GHRH), which could redirect future studies. Schally worked with Jozsef L. Varga, Ph.D., research associate professor of medicine in the Division of Hematology Oncology and researcher at the Miami Veterans Affairs Medical Center. The findings are the result of a collaboration with researchers at the University of Santiago de Compostela, Spain, led by Felipe F. Casanueva, M.D., Ph.D., and are published in the December 15 edition of the Proceedings of the National Academy of Sciences.
Growth hormone is normally released by the pituitary to help the body’s skeletal system and muscle mass develop. Its function is at its highest during adolescence when children experience a high rate of growth. In past studies, Schally, a professor of medicine in the Division of Hematology Oncology at the Sylvester Comprehensive Cancer Center, has shown that growth hormone also plays a role in fueling the growth of several cancer lines.
Because of growth hormone’s normal impact on the body and its potential to trigger the proliferation of cancer cells, scientists have long been interested in determining exactly what factors regulate its release in the body. Decades ago, researchers discovered that growth hormone-releasing hormone (GHRH), which stimulates the secretion of growth hormone, and somatostatin, which inhibits its release, were two factors. In 2001, scientists discovered another peptide which stimulates secretion: ghrelin. That has led endocrinologists to examine how these three factors interact.
For GHRH and ghrelin, the two known stimulators of growth hormone, to exert their action normally, they must bind to a receptor, which lies in the pituitary. Scientists believed that each factor would only bind to its own corresponding receptor. Surprisingly, this international team of researchers found that GHRH acts on the ghrelin receptor in addition to its own receptor. “This finding,” says Schally, “demonstrates another element in the regulation of growth hormone that we must now pursue.”
Researchers now plan to focus on how growth hormone-releasing hormone acts on the ghrelin receptor. “We must learn how these factors interact, if we are to find a way to control them,” says Schally, who has dedicated much of his research over the last 15 years to synthesizing GHRH antagonists which bind to the GHRH receptor and block the growth hormone activity. These antagonists have also been shown to bind to GHRH receptors within cancer cells, thereby blocking the effects of local growth hormone-releasing hormone which would have otherwise fueled the tumor.
This study brings together a number of elements for future direction. Scientists have already determined that some cancer cells have receptors for GHRH and ghrelin. Schally and his laboratory have previously found that GHRH antagonists block the growth hormone-releasing hormone receptor. Knowing that GHRH acts on the ghrelin receptor, researchers will now take a closer look at whether GHRH antagonists will block ghrelin receptors within cancer cells accordingly. “This will take us another step closer to finding a therapy for cancer,” says the Nobel laureate.