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STRESS HORMONE RESEARCH
By Sean Henahan, Access Excellence
BETHESDA- New understanding of how the " stress hormone" (corticoptropin releasing hormone or CRH) acts on the body's immune and nervous system could open up new methods for the treatment of infection, inflammation, cancer and perhaps AIDS, according to Julio Licinio, MD and associates, Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health (NIH). It is already known that the hormone, which contains 41 amino acids acts as a mediator for many different behavioral and physiological responses to stress. However, the NIH team has found that a gene sequence which controls production of a substance called pro-opiomelanocortin (POMC)is a major molecular target of the corticotropin-releasing hormone. Corticotropin-releasing hormone ) is one of many stress responsive substances that influence response to pathogens and susceptibility to disease. It is present in the hypothalamus, the section of the brain responsible for stress and emotion and it also acts at peripheral sites as a modulator of the body's immune defenses, said Dr. Licinio. " Because of these actions, CRH is an important mediator of the interactions between the nervous system of the nervous system and the nervous system," he said. The NIH team has identified three transcription factors in pituitary cells treated with CRH which affect transcription of the POMC gene. They also found that transcription factors bind to two different sites within the portion of the CRH molecule that is normally responsive to POMC. Specifically, the transcription factors are known as include CRH-responsive element binding protein (PCRH-REB-1), a related factor called POGA and another called PO-B. When they searched the enormous "Genbank", which contains detailed information on the genetic sequences regulating the production and function of many different biological substances, they were able to find the same three transcription factors in the genome of HIV-1, human breast cancer oncogenes, and the gene encoding for the inflammation mediator interleukin-1 beta converting enzyme. For example, they found that the specific gene sequence of PCRH-GE is 100% homologous to a region of the HIV-1 genome located just before the gag-gene, an area known to respond to host transcription factors that affect viral replication. " We hypothesize a mechanism of hormone action by which a peptide hormone , such as CRH, might affect disease susceptibility by eliciting production of transcription factors which may bind to unexpected intracellular targets. These might include viruses, oncogenes, or the genes encoding for inflammatory mediators, infection, inflammation and possibly neoplastic transformation would thus be facilitated," Dr. Licinio said, adding: " This hypothesis can be tested, and if confirmed, CRH antagonists may prove useful in the treatment of disorders whose pathophysiology involves molecules that respond to CRH-regulated POMC transcription factors. " Infection, inflammation and cancer are a sequence of multiple events occurring at the molecular and cellular levels. Identifying each event and characterizing the complex interactions would result in one of the most promising, but challenging areas of current biomedical research." For more details of this research see: Licinio et al, The Lancet, Vol.346, July 8, 1995, pp. 104-106.
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