A molecular mechanism for stress-induced alterations in susceptibility to disease

• Published in: The Lancet (British edition) Vol. 346; no. 8967; pp. 104 - 106
• Main Authors: Licinio, J, Gold, P.W, Wong, M-L
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 08.07.1995; Lancet; Elsevier Limited
• Subjects: AIDS/HIV; Antagonists; Base Sequence; Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - genetics; Corticotropin-Releasing Hormone - metabolism; Cytomegalovirus; Cytomegalovirus - genetics; Endocrinopathies; Genetic Predisposition to Disease; Genetic transformation; Genome, Viral; Genomes; HIV; HIV-1 - genetics; Hormones; Human immunodeficiency virus; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); IL-1β; Immunity (Disease); Inflammation; Inflammation Mediators - metabolism; Interleukins; Medical sciences; Molecular biology; Molecular Sequence Data; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Oncogenes - genetics; Peptides; Physiological responses; Pro-Opiomelanocortin - genetics; Promoter Regions, Genetic - genetics; Proopiomelanocortin; Protein-Tyrosine Kinases - genetics; Proto-Oncogenes - genetics; Regulatory sequences; Sequence Homology, Nucleic Acid; Sequences; Stress; Stress, Physiological - genetics; Transcription factors; Transcription Factors - genetics; Human; Hypothalamic hormone; Gene; Nucleotide sequence; ACTH-RH; Peptide hormone; Proopiocortin; Hormone releasing factor; Transcription factor; Mechanism of action; Stress
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(95)92119-2

Summary Corticotropin-releasing hormone (CRH) is a 41-aminoacid peptide which mediates behavioural and physiological responses to stress. A major target of CRH is the pro-opiomelanocortin (POMC) gene. Three transcription factors have been identified that affect transcription of the POMC gene by binding to two different sites within the CRH-responsive element of that promoter. We searched Genbank and found that nucleotide sequences in the POMC promoter which bind POMC-transcription factors are also contained in the genome of HIV-1 and cytomegalovirus, in c-fes and human MAT-1 breast cancer oncogenes, and in proinflammatory molecules, such as the interleukin-1β converting enzyme. We hypothesise a mechanism of hormone action by which a peptide hormone, such as CRH, might affect disease susceptibility by eliciting the production of transcription factors which may bind to unexpected intracellular targets, such as viruses, oncogenes, or the genes encoding for inflammatory mediators. Infection, inflammation, and possibly neoplastic transformation would thus be facilitated. This hypothesis can be tested. If confirmed, CRH antagonists may prove useful in the treatment of disorders whose pathophysiology involves molecules that respond to CRH-regulated POMC transcription factors.