Immunohistochemical Localization of the Glucocorticoid Receptor in Pancreatic β- Cells of the Rat*

Abstract

We used a monoclonal antibody against an epitope located in the N-terminal moiety of the rat glucocorticoid receptor to identify the glucocorticoid receptor-containing cells in the rat pancreas. Monospecific polyclonal antisera against insulin, glucagon, somatostatin, and amylase were applied to serial sections in colocalization studies to identify the respective endocrine and exocrine cells. Glucocorticoid receptor immunoreactivity was exclusively present in nuclei and cytoplasm of the beta-cells of pancreatic islets. Western blots using the glucocorticoid receptor antibody resulted in identical 94K immunoreactive proteins in both liver and pancreas. After adrenalectomy, the glucocorticoid receptor immunoreactivity of beta-cells decreased significantly. A computer-assisted method of semiquantitative evaluation of the glucocorticoid receptor immunoreactivity demonstrated a significant decrease in the staining intensity of the beta-cells by 23.5% and in that of insulin antibodies by 10.4%, while amylase immunoreactivity was only slightly decreased. Serum levels of corticosterone determined by RIA decreased from 225 micrograms/ml in sham-operated animals to 55 micrograms/ml in animals 14 days after adrenalectomy, while the tissue content of amylase decreased by 45%. The immunohistochemical findings give circumstantial evidence of the presence of glucocorticoid receptor in beta-cells. We interpret our data as indicating an indirect effect of glucocorticoids on amylase synthesis via a glucocorticoid-insulin-exocrine cell pathway.

11β-Hydroxysteroid dehydrogenase type 1 regulates insulin and glucagon secretion in pancreatic islets

“…Species differences in expression may be important and our observations with regard to GR abundance would endorse this. We observed GR immunoreactivity throughout the whole murine islet and not exclusively in the beta cells as reported in rat tissue [7].…”

“…GR immunoreactivity has been found to be exclusively present in the nuclei and cytoplasm of beta cells of rat pancreatic islets [7]. The effects of glucocorticoid on insulin secretion are dependent upon the dose and duration of administration [8].…”

Repeated maternal glucocorticoid administration and the developing liver in fetal sheep

“…GR are present in the cells of the adult pancreas (Fischer et al 1990) and glucocorticoids have been shown to regulate pancreatic development (Rall et al 1977, Hill 1999. Furthermore, it has been shown previously that glucocorticoids inhibit insulin secretion from cultured adult mouse islets (Lambillote et al 1997).…”

Islet amyloid polypeptide in the islets of Langerhans: friend or foe?

“…After dexamethasone treatment, alterations in beta-cell gene expression presumably occur in response to the metabolic perturbations but the steroid could act also by a direct effect on the beta cell because rat beta cells express glucocorticoid receptors [72]. The differential effect on IAPP and insulin gene expression could be explained by the presence of a negative regulatory element in the insulin gene promoter, which is lacking in the IAPP gene promoter and which binds dexamethasone [73].…”