NEUROTOXIC LESIONS INDUCED BY MONOSODIUM GLUTAMATE RESULT IN INCREASED ADENOPITUITARY PROOPIOMELANOCORTIN GENE-EXPRESSION AND DECREASED CORTICOSTERONE CLEARANCE IN RATS

Hypothalamic-pituitary-adrenocortical function in rats with brain lesi ons induced by neonatal monosodium glutamate (MSG) treatment (4 mg/g, 5 administrations, i.p.) was evaluated in the present study. Using in situ hybridization we found increased proopiomelanocortin (POMC) mRNA levels in the adenopituitary and normal corticotropin-releasing hormon e mRNA levels in the hypothalamic paraventricular nucleus in MSG-treat ed rats. The total content of pituitary adrenocorticotropin (ACTH) was not changed, while pituitary ACTH concentration was higher in MSG-tre ated compared to control rats. The number of ACTH-immunostained cells per a constant area of adenohypophysial section, as measured by immuno histochemistry, was unchanged indicating that no significant condensat ion of corticotropes occurred. Basal plasma ACTH concentrations were n ot different, whereas morning corticosterone levels were elevated in r ats with MSG treatment. While ACTH response to stress stimuli was simi lar in both groups of rats, corticosterone response to exogenous ACTH (500 ng/kg, i.v., Synacthen), short-lasting handling and immobilizatio n was of the same magnitude but prolonged in MSG-treated rats. Based o n the decline of [H-3]corticosterone in plasma, a decreased corticoste rone clearance rate was found in MSG-treated rats. These findings sugg est that MSG treatment results in increased POMC gene expression per c orticotrope of the atrophic pituitary resulting in maintenance of norm al pituitary ACTH stores and plasma ACTH levels. Elevated basal levels of corticosterone in plasma as well as prolonged corticosterone respo nses to stimulations in rats treated with MSG seem to be due to a decr eased clearance rate of corticosterone.