The effect of hypophysectomy on pancreatic islet hormone and insulin-like growth factor I content and mRNA expression in rat

Abstract

The growth arrest after hypophysectomy in rats is mainly due to growth hormone (GH) deficiency because replacement of GH or insulin-like growth factor (IGF) I, the mediator of GH action, leads to resumption of growth despite the lack of other pituitary hormones. Hypophysectomized (hypox) rats have, therefore, often been used to study metabolic consequences of GH deficiency and its effects on tissues concerned with growth. The present study was undertaken to assess the effects of hypophysectomy on the serum and pancreatic levels of the three major islet hormones insulin, glucagon, and somatostatin, as well as on IGF-I. Immunohistochemistry (IHC), in situ hybridization (ISH), radioimmunoassays (RIA), and Northern blot analysis were used to localize and quantify the hormones in the pancreas at the peptide and mRNA levels. IHC showed slightly decreased insulin levels in the b cells of hypox compared with normal, age-matched rats whereas glucagon in a cells and somatostatin in d cells showed increase. IGF-I, which localized to a cells, showed decrease. ISH detected a slightly higher expression of insulin mRNA and markedly stronger signals for glucagon and somatostatin mRNA in the islets of hypox rats. Serum glucose concentrations did not differ between the two groups although serum insulin and C-peptide were lower and serum glucagon was higher in the hypox animals. These changes were accompanied by a more than tenfold drop in serum IGF-I. The pancreatic insulin content per gram of tissue was not significantly different in hypox and normal rats. Pancreatic glucagon and somatostatin per gram of tissue were higher in the hypox animals. The pancreatic IGF-I content of hypox rats was significantly reduced. Northern blot analysis gave a 2.6-, 4.5-, and 2.2-fold increase in pancreatic insulin, glucagon, and somatostatin mRNA levels, respectively, in hypox rats, and a 2.3-fold decrease in IGF-I mRNA levels. Our results show that the fall of serum IGF-I after hypophysectomy is accompanied by a decrease in pancreatic IGF-I peptide and mRNA but by partly discordant changes in the serum concentrations of insulin and glucagon and the islet peptide and/or mRNA content of the three major islet hormones. It appears that GH deficiency resulting in a ''low IGF-I state'' affects translational efficiency of these hormones as well as their secretory responses. The maintenance of normoglycemia in the presence of reduced insulin and elevated glucagon serum levels, both of which would be expected to raise blood glucose, may result mainly from the enhanced insulin sensitivity, possibly due to GH deficiency and the subsequent decrease in IGF-I production.

Regulation of Pancreatic Islet Beta-Cell Mass by Growth Factor and Hormone Signaling

“…IGF-1R and key IGF-1 signaling components are present and functional in islets. [116][117][118] This somewhat supports direct effect of GH (independent of IGF-1) on beta-cell proliferation 71 (see Section 2.2 earlier). 115 However, several studies have shown that IGF-1 appears to be specifically localized to alpha cells in the islets.…”

Growth hormone (GH) treatment acts on the endocrine and autocrine/paracrine GH/IGF-axis and on TNF-α expression in bony fish pituitary and immune organs

“…Plasma was removed and stored at À20 C. Plasma IGF-I levels were determined in undiluted samples by RIA after SepPak C18 chromatography (Waters Corp., Milford, MA, USA), as described earlier for mammals [57]. In brief, 0.15 ml PBS containing 0.2% human serum albumin (HSA), pH 7.4, was added to 0.1 ml plasma.…”

Insulin-like growth factor I is expressed in classical and nodular lymphocyte-predominant Hodgkin’s lymphoma tumour and microenvironmental cells

“…Subsequently, the antibody against CD30 was applied overnight at 4°C and visualised with Texas-red-conjugated goat anti-mouse IgG. Specificity of the antisera was tested by omitting the primary antisera as a negative control and by using sections of human breast cancer, intestine and lymph node and rat pancreas as positive controls as previously described (Eppler et al 2002;Jevdjovic et al 2004Jevdjovic et al , 2005Oberlin et al 2009;Link et al 2013) and an embryonic tumour known to contain CD30-immunoreactive cells.…”