Regulation of the Central Nervous System-Pituitary-Adrenal Axis in Rats after Neonatal Treatment with Monosodium Glutamate

Abstract

We have studied the regulation of adrenal function in male rats treated neonatally with monosodium glutamate (MSG) and in littermate controls. When 6–7 months old, MSG-treated rats presented reduced body, adrenal and pituitary weight, obesity, atrophy of the optic nerve and damage of the arcuate nuclei (ARN) of the hypothalamus. MSG-treated rats showed increased serum corticosterone (CORT) levels under resting conditions; after ether stress the increase in serum CORT was greater in MSG animals when compared to littermate controls. Plasma ACTH followed the same trend although it reached significance after ether stress only. Both circulating CORT and ACTH were normally suppressed by dexamethasone (DEX) administration. Levels of corticosteroid binding globulin were also increased, whereas daily circadian rhythm of serum CORT was blunted. We also determined cytosolic receptors in areas suggested to participate in the negative feedback of glucocorticoids at the central level. Binding of (³H)-DEX in MSG rats was similar to controls in hippocampus, whole hypothalamus and anterior pituitary, but a significant reduction (≈ 50%) was obtained after microdissection in the area normally occupied by the ARN, without changes in the ventromedial nuclei of the hypothalamus. These results suggest that the ARN may be involved in the regulation of the pituitary-adrenal axis, although the abnormalities observed in the MSG syndrome partially differ from those in rats with hippocampal damage, previously studied in our laboratory.

The sensitivity of male rat reproductive organs to monosodium glutamate

“…MSG has been demonstrated to exert neuronal toxic e ects in the central nervous system (CNS), including the hypothalamopituitary (HP) axis (3,(20)(21)(22)(23). e plasma levels of gonadotropic hormones (FSH and LH) and testosterone, and the total number of Leydig cells have been reported to be signi cantly decreased in prepubertal rats treated with 4 mg/kg body weight of MSG (9).…”

Chronic Administration of Monosodium Glutamate under Chronic Variable Stress Impaired Hypothalamic-Pituitary-Adrenal Axis Function in Rats

“…However, previous studies have also proven that alterations in the central nervous system (CNS)-pituitary-adrenal axis (including an increase in serum levels of corticosterone and ACTH) as well as in the nerve growth factor (NGF) and neuropeptide Y (NPY) concentrations in the hypothalamic and pituitary glands can be induced in MSG-treated neonatal rats [8,9]. Furthermore, several researchers have reported that systemic or dietary MSG administration caused prominent increases in the glutamate levels in adult animals, although there were some differences between glutamate levels in the plasma and cerebrospinal fluid (CSF) depending on the administration route [10,11].…”

Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female 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.…”