Cell-specific precursor processing.
The singular gene for a peptide hormone is expressed not only in a specific endocrine cell type but also in other endocrine cells as well as in entirely different cells such as neurons, adipocytes, myocytes, immune cells, and cells of the sex-glands. The cellular expression pattern for each gene varies with development, time and species. Endocrine regulation is, however, based on the release of a given hormone from an endocrine cell to the general circulation from whose cappilaries the hormone reaches the specific target cell elsewhere in the body. The widespread expression of hormone genes in different cells and tissues therefore requires control of biogenesis and secretion in order to avoid interference with the function of a specific hormonal peptide from a particular endocrine cell. Several mechanisms are involved in such control, one of them being cell-specific processing of prohormones. The following pages present four examples of such cell-specific processing and the implications of the phenomenon for the use of peptide hormones as markers of diseases. Notably, sick cells - not least the neoplastic cells - often process prohormones in a manner different from that of the normal endocrine cells.
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 2100, Copenhagen, Denmark. jens.f.rehfeld@rh.regionh.dk
Jens F
JF
Rehfeld
Jens R
JR
Bundgaard
D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism; D004703:Endocrine System; D005755:Gastrins / Q000378:metabolism; D005786:Gene Expression Regulation; D006728:Hormones / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism; D009496:Neurotensin / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D052336:Proglucagon / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D015398:Signal Transduction
D005755:Gastrins; D006728:Hormones; D010455:Peptides; D011498:Protein Precursors; D009496:Neurotensin; C013706:big gastrin; D052336:Proglucagon; D002766:Cholecystokinin