Signal transduction in endocrine cells

Abstract

Endocrine Patholog~ vol. 6, no. 4, 247-251, November 1995 9 Copyright 1995 by Humana Press Inc. All rights of any nature whatsoever reserved. 1046-3976/95/6:247-251/$5.00 The field of endocrine pathology has always been situated at the intersection of anatomical pathology and basic biology. In the early days of immunohistochemistry, the detection of excessive hormone production in pituitary tumors provided an insight into the metabolic disturbances of endocrine abnormalities ranging from acromegaly to galactorrhea. The discovery that a variety of tumors expressed ectopic hormones provide a firm understanding of the range of clinical symptoms seen in many cancer patients. For example, carcinoid tumors appear well behaved microscopically, but with the aid of immunohistochemistry they are seen as factories working overtime to synthesize and package a wide variety ofbioactive products. The differentiated nature of many endocrine tumors has provided researchers with a rich resource to identify and characterize signaling molecules at a time when most human diseases were not approachable using molecular techniques. For example, an insulinoma provided the source of messenger RNA necessary to clone the gene for human insulin, and the first three human genes that were cloned-growth hormone, insulin, and somatostatin--were of endocrine origin. The high level of expression of RNAs encoding functional hormones is a common property of endocrine cells and their study has provided the pathologist access to the challenging world of molecular biology. Many of the early developments in in situ hybridization came from examining endocrine tissues [1]. The initial studies ofectopic expression of hormones in gastrointestinal malignancies [2,3], small cell carcinomas [4], and neuroblastomas are a few of the early demonstrations of the value of the marriage of anatomical pathology and molecular biology: Today the field of molecular biology has made great advances in techniques as well as understanding, so that the immunohistochemical and in situ hybridization techniques that were developed using differentiated endocrine tumors now provide researchers insights into the most intractable clinical problems from detection of viral sequences within a single cell to the identification of an oncogenic mutation within a paraffin-embedded tumor. However, as biology enters a new age of understanding, endocrine pathology continues to occupy an important position both to the researcher and clinician. The greatest area of growth in biology over the last 10 yr is in the field of signal transduction: How extracellular signals convey information to the cell and the nucleus to initiate programs of differentiation and cell growth [5]. The discovery of cascades of phosphorylation and the identification of large-signaling complexes has changed the way researchers understand how cells react to the environment [6]. Classical pathways have become a dizzying network of proteins that "cross-talk" with each other to create a large array of interlocking signals and feedback loops that make most of us long for the days when G-proteins appeared only to regulate cAMP levels and oncogenes were confined to the distant world of viruses.