title: The glucocorticoid receptor and its expression in the anterior pituitary and the adrenal cortex: a source of variation in hypothalamic-pituitary-adrenal axis function; implications for pituitary and adrenal tumors.
abstract: OBJECTIVE
  To review the expression of the glucocorticoid receptor (GR) in anterior pituitary and adrenocortical cells and tumors derived from these tissues as well as factors that may influence its expression.
  
  
  METHODS
  We present an overview of the relevant literature, with a focus on data generated from our studies.
  
  
  RESULTS
  The expression of the GR is an essential element of the negative feedback that closes the loop formed by corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol in the context of the hypothalamic-pituitary-adrenal (HPA) axis. Although the GR expression in anterior pituitary cells-and in particular the corticotrophs-was first demonstrated several years ago, it was not known until relatively recently where, by what cells, and in what form the GR is expressed in the adrenal cortex. The variability in the expression of the GR in pituitary and adrenocortical cells may underlie the substantial differences in HPA axis function across individuals, especially when testing for tumors associated with hypercortisolemia. This expression is influenced by a multitude of tissue-specific factors, which may explain why it is so difficult to interpret (or reproduce) studies that are based on GR functional polymorphisms on different cohorts of patients or even different sets of laboratory animals.
  
  
  CONCLUSIONS
  This review highlights the variability in expression and function of the GR in pituitary and adrenocortical cells as one of the reasons for the appreciable differences in HPA axis function across individuals. Particular attention was paid to interactions that may affect the interpretation of diagnostic testing of the HPA axis in patients with pituitary adenomas (Cushing disease) or adrenocortical tumors (Cushing syndrome).
authors: Pediatric Intensive Care Unit, University Hospital of Heraklion, Heraklion, Crete, Greece.
authors: George
authors: G
authors: Briassoulis
authors: Svetozar
authors: S
authors: Damjanovic
authors: Paraskevi
authors: P
authors: Xekouki
authors: Hervé
authors: H
authors: Lefebvre
authors: Constantine A
authors: CA
authors: Stratakis
mesh_terms: D000302:Adrenal Cortex / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D003480:Cushing Syndrome / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology* / Q000503:physiopathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D047748:Pituitary ACTH Hypersecretion / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000502:physiology* / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*
chemical_list: C497713:NR3C1 protein, human; D009363:Neoplasm Proteins; D011965:Receptors, Glucocorticoid