Neurotoxic Lesions Induced by Monosodium Glutamate Result in Increased Adenopituitary Proopiomelanocortin Gene Expression and Decreased Corticosterone Clearance in Rats

Abstract

Hypothalamic-pituitary-adrenocortical function in rats with brain lesions 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 hormone mRNA levels in the hypothalamic paraventricular nucleus in MSG-treated rats. The total content of pituitary adrenocorticotropin (ACTH) was not changed, while pituitary ACTH concentration was higher in MSG-treated compared to control rats. The number of ACTH-immunostained cells per a constant area of adenohypophysial section, as measured by immunohistochemistry, was unchanged indicating that no significant condensation of corticotropes occurred. Basal plasma ACTH concentrations were not different, whereas morning corticosterone levels were elevated in rats with MSG treatment. While ACTH response to stress stimuli was similar in both groups of rats, corticosterone response to exogenous ACTH (500 ng/kg, i.v., Synacthen), short-lasting handling and immobilization was of the same magnitude but prolonged in MSG-treated rats. Based on the decline of [³H]corticosterone in plasma, a decreased corticosterone clearance rate was found in MSG-treated rats. These findings suggest that MSG treatment results in increased POMC gene expression per corticotrope of the atrophic pituitary resulting in maintenance of normal pituitary ACTH stores and plasma ACTH levels. Elevated basal levels of corticosterone in plasma as well as prolonged corticosterone responses to stimulations in rats treated with MSG seem to be due to a decreased clearance rate of corticosterone.

Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats

“…21 Conversely, circulating FB concentrations were significantly higher in MSG than in CTR rats. Additionally, reduced corticosterone clearance rate 9,10 and increased fasciculata to glomerolosa width ratio 11 have been reported in MSG rats.…”

“…2,3,4,6,7 Also, the changes in hypothalamic neuronal function particularly enhance hypothalamo-pituitary-adrenal (HPA) axis activity. [8][9][10][11][12] It is known that hypophagic, 13 MSG-damaged rats are characterized by increased adiposity and insulin resistance; 14 however, the exact mechanisms whereby these abnormalities develop are not fully understood. These MSG-induced changes in HPA axis activity, a key function for maintaining homeostasis, have been attributed to dysfunctions of several hypothalamic peptidergic and monoaminergic systems [15][16][17] driving pituitary function, and, in turn, modifying adrenal development and function, 11 thus resulting in enhanced corticoadrenal activity.…”

“…These MSG-induced changes in HPA axis activity, a key function for maintaining homeostasis, have been attributed to dysfunctions of several hypothalamic peptidergic and monoaminergic systems [15][16][17] driving pituitary function, and, in turn, modifying adrenal development and function, 11 thus resulting in enhanced corticoadrenal activity. [8][9][10][11][12] The bi-directional crosstalk between HPA axis and adipose tissue activities is widely accepted. 18 We recently demonstrated that the peripheral satiety signal leptin, 19 a physiological inhibitor of ACTH-driven adrenal glucocorticoid production, 20 is several fold increased in the circulation of MSG rats shortly after the end of treatment, and is even more pronounced at adulthood.…”

Neuroendocrine, Metabolic, and Immune Functions during the Acute Phase Response of Inflammatory Stress in Monosodium <i>L</i>-Glutamate-Damaged, Hyperadipose Male Rat

“…In fact, as a consequence of prolonged hyperleptinemia [13] a down-regulation of adrenal Ob-Rb expression [26] takes place. This abnormality contributes with the characteristic corticoadrenal hyperactivity [34] and reduced clearance rate of glucocorticoid in MSG animals [35]. The adult phenotype in animals treated neonatally with MSG seems to be directly dependent on elevated corticosteroid levels.…”

Monosodium Glutamate Toxic Effects and Their Implications for Human Intake: A Review

“…Increased proopiomelanocortin mRNA levels and adrenocorticotropic hormone concentration in the adenopituitary have been found in neonatal MSG-treated rats compared with controls (4 mg/g, 5 administrations intraperitoneally) (Skultetyova et al 1998). Furthermore, numerous studies have shown that neonates treated with MSG exhibited neuronal cell death with reduction of photoreceptor and glial cells (Blanks et al 1981, Reif-Lehrer et al 1975, Regan et al 1981, Hyndman and Adler 1981.…”