title: Dysregulation of corticosterone secretion in streptozotocin-diabetic rats: modulatory role of the adrenocortical nitrergic system.
abstract: An increased activity of the hypothalamo-pituitary-adrenal axis resulting in exaggerated glucocorticoid secretion has been repeatedly described in patients with diabetes mellitus and in animal models of this disease. However, it has been pointed out that experimental diabetes is accompanied by a decreased glucocorticoid response to ACTH stimulation. Because previous studies from our laboratory demonstrate the involvement of nitric oxide (NO) in the modulation of corticosterone production, present investigations were designed to evaluate 1) the impact of streptozotocin (STZ)-induced diabetes on the adrenocortical nitrergic system and 2) the role of NO in the modulation of adrenal steroidogenesis in STZ-diabetic rats. Four weeks after STZ injection, increased activity and expression levels of proteins involved in L-arginine transport and in NO synthesis were detected, and increased levels of thiobarbituric acid reactive species, carbonyl adducts, and nitrotyrosine-modified proteins were measured in the adrenocortical tissue of hyperglycemic rats. An impaired corticosterone response to ACTH was evident both in vivo and in adrenocortical cells isolated from STZ-treated animals. Inhibition of NO synthase activity resulted in higher corticosterone generation in adrenal tissue from STZ-treated rats. Moreover, a stronger inhibition of steroid output from adrenal cells by a NO donor was observed in adrenocortical Y1 cells previously subjected to high glucose (30 mM) treatment. In summary, results presented herein indicate an inhibitory effect of endogenously generated NO on steroid production, probably potentiated by hyperglycemia-induced oxidative stress, in the adrenal cortex of STZ-treated rats.
authors: Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Centro de Estudios Farmacológicos y Botanicos-Consejo Nacional de Investigaciones Científicas y Técnicas (CEFYBO-CONICET), Buenos Aires, Argentina.
authors: E M
authors: EM
authors: Repetto
authors: R
authors: R
authors: Sanchez
authors: J
authors: J
authors: Cipelli
authors: F
authors: F
authors: Astort
authors: C Martinez
authors: CM
authors: Calejman
authors: G G
authors: GG
authors: Piroli
authors: P
authors: P
authors: Arias
authors: C B
authors: CB
authors: Cymeryng
mesh_terms: D000302:Adrenal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D009569:Nitric Oxide; D013311:Streptozocin; D000324:Adrenocorticotropic Hormone; D019001:Nitric Oxide Synthase; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone