Evidence that elevated plasma corticosterone levels are the cause of reduced hypothalamic corticotrophin-releasing hormone gene expression in diabetes

Regulatory Peptides
M W SchwartzM F Dallman

Abstract

Uncontrolled diabetes mellitus causes both a sustained activation of the hypothalamic-pituitary-adrenal (HPA) axis and reduced expression of corticotrophin-releasing hormone (CRH) mRNA in the hypothalamic paraventricular nucleus (PVN). To investigate the role of glucocorticoids in the regulation of CRH mRNA expression in the PVN of diabetic rats, we studied surgically adrenalectomized (ADX) and sham-operated male Sprague-Dawley rats 4 days after i.v. injection of streptozotocin (STZ; 65 mg/kg i.v.) or vehicle. Among sham-operated animals, AM plasma corticosterone levels were significantly increased in diabetic as compared to nondiabetic animals (1.46+/-0.54 vs. 0.22+/-0.05 microg/dl; P <0.05), and were positively correlated to both plasma ACTH levels (r = 0.74; P = 0.015) and adrenal gland weight (r = 0.70; P = 0.025). In contrast, CRH mRNA levels measured in the PVN by in situ hybridization were inversely related to the plasma corticosterone level (r = -0.68; P = 0.045). In a second experiment, both diabetic and nondiabetic ADX rats received a continuous subcutaneous infusion of either corticosterone at one of two doses or its vehicle for 4 days. Among vehicle-treated ADX animals, STZ diabetes raised hypothalamic CRH mRNA leve...Continue Reading

References

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Citations

Apr 6, 2004·Biochemical and Biophysical Research Communications·Katsutaka OishiNorio Ishida
Oct 12, 2000·Neuroscience Letters·J Jackson-GuilfordL K Nisenbaum
May 31, 2013·The Journal of Endocrinology·Nicole Uschold-SchmidtStefan O Reber
Aug 12, 2000·Stress : the International Journal on the Biology of Stress·S F AkanaM F Dallman
Nov 4, 2015·The Journal of Clinical Investigation·Gregory J MortonMichael W Schwartz
Mar 13, 2016·Diabetologia·Thomas H Meek, Gregory J Morton
Jun 11, 2005·Journal of Neuroendocrinology·K ProulxR J Seeley
Dec 23, 2004·Journal of Periodontal Research·Torbjørn BreivikFrode Fonnum
Nov 26, 2010·Physiology & Behavior·Isabell J SchererRuth B S Harris
Mar 18, 2010·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Raja RezgNajoua Gharbi
Apr 29, 2010·Diabetes·Jonathan P GermanGregory J Morton
Aug 28, 2003·Diabetes·Susanne E la FleurMary F Dallman
Sep 8, 2005·American Journal of Physiology. Endocrinology and Metabolism·Dóra ZelenaGábor B Makara
Apr 29, 2015·Nature Communications·Rachel J PerryGerald I Shulman
Dec 19, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Ruth B S Harris
Oct 9, 2002·Journal of Periodontal Research·T BreivikT Myhrer
Nov 28, 2001·Journal of Neuroendocrinology·T KanedaK Hashimoto
Jul 10, 2017·Animal Cells and Systems·Yun-Beom SimHong-Won Suh

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