Glucocorticoid Receptor Expression in Nontumorous Human Pituitaries and Pituitary Adenomas

Abstract

Glucocorticoids have multiple actions, including a suppressive feedback effect on pituitary corticotrophs via the glucocorticoid receptor (GR). By immunocytochemistry, we studied GR expression in 86 surgically removed various pituitary adenoma types. Ten cases contained nontumorous pituitary fragments, which were suitable for immunocytochemical investigation. In addition, 30 autopsy-obtained pituitaries, 10 of them containing incidental microadenomas, were examined as well. Using a polyclonal GR antibody, the streptavidin-biotin-peroxidase complex method revealed nuclear and/or cytoplasmic GR immunoreactivity in many nontumorous corticotrophs and other adenohypophysial cell types and in S-100 protein immunopositive stellate cells. Cellular localization was confirmed by double immunostaining. Pars intermedia corticotrophs, posterior lobe axons, Herring bodies, and pituicytes as well as several endothelial cells lining the capillaries were also immunopositive. GR immunoreactivity was also demonstrated in many GH, PRL, ACTH, TSH, FSH, LH α-subunit producing adenomas, null cell adenomas, and oncocytomas. The extent and degree of immunostaining varied considerably from case to case. Suppressed corticotrophs showing the Crooke’s hyaline change due to glucocorticoid excess were present in the nontumorous pituitaries of patients with Cushing’s disease and in those treated with pharmacologic doses of glucocorticoids. Many suppressed nontumorous corticotrophs exhibited only weak or no GR immunopositivity, indicating GR downregulation accompanied by cellular injury. Study of autopsy obtained pituitaries for GR yielded inconclusive results indicating that autopsy obtained adenohypophyses are not suitable for the immunocytochemical investigation of GR.