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.

Keywords:
Monosodium glutamate, Proopiomelanocortin, Corticotropin, Adrenal steroids, Stress, Arcuate nucleus
1.
Olney JW: Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 1969;164:719–721.
2.
Redding TW, Schally AV, Arimura A, Wakabayashi I: Effect of monosodium glutamate on some endocrine functions. Neuroendocrinology 1971;8:245–255.
3.
Nemeroff CB, Konkol RJ, Bissette G, Youngblood W, Martin JB, Brazeau P, Rone MS, Prange AJ Jr, Breese GR, Kizer JS: Analysis of the disruption in hypothalamic-pituitary regulation in rats treated neonatally with monosodium L-glutamate (MSG): Evidence for the involvement of tuberoinfundibular cholinergic and dopaminergic systems in neuroendocrine regulation. Endocrinology 1977;101:613–622.
4.
Klingberg H, Brankačk J, Klingberg F: Long-term effects on behavior after postnatal treatment with monosodium-L-glutamate. Biomed Biochim Acta 1987;46:705–711.
5.
Krieger DT, Liotta AS, Nicholsen G, Kizer JS: Brain ACTH and endorphin reduced in rats with monosodium glutamate-induced arcuate nuclear lesions. Nature 1979;278:562–563.
6.
Conte-Devolx B, Giraud P, Castanas E, Boudouresque F, Orlando M, Gillioz P, Oliver C: Effects of neonatal treatment with monosodium glutamate on the secretion of α-MSH, β-endorphin and ACTH in the rat. Neuroendocrinology 1981;33:207–211.
7.
Ács Z, Antoni FA, Makara GB: Corticoliberin and somatoliberin activity in the pituitary stalk median eminence of rats after neonatal treatment with monosodium glutamate. J Endocrinol 1982;93:239–245.
8.
Liu HC, Chen QL, Gu F: Influence of hypothalamic arcuate nucleus lesion with monosodium glutamate on plasma corticosterone in neonatal rats. Acta Pharmacol Sin 1986;7:104–105.
9.
Spinedi E, Johnston C, Negro-Vilar A: Increased responsiveness of the hypothalamic-pituitary axis after neurotoxin-induced hypothalamic denervation. Endocrinology 1984;115:267–272.
10.
Tokuyama K, Himms-Hagen J: Brown adipose tissue thermogenesis, torpor and obesity of glutamate-treated mice. Am J Physiol 1986;251:E407–E415.
11.
Magarinos AM, Estivariz F, Morado MI, De Nicola AF: Regulation of the central nervous system-pituitary-adrenal axis in rats after neonatal treatment with monosodium glutamate. Neuroendocrinology 1988;48:105–111.
12.
Dolnikoff MS, Kater CE, Egami M, De Andrade IS, Marmo MR: Neonatal treatment with monosodium glutamate increases plasma corticosterone in the rat. Neuroendocrinology 1988;48:645–649.
13.
Larsen PJ, Mikkelsen JD, Jessop D, Lightman SL, Chowdrey HS: Neonatal monosodium glutamate treatment alters both the activity and the sensitivity of the rat hypothalamo-pituitary-adrenocortical axis. J Endocrinol 1994;141:497–503.
14.
Ježová D, Tokarev D, Rusnák M: Endogenous excitatory amino acids are involved in stress-induced adrenocorticotropin and catecholamine release. Neuroendocrinology 1995;62:326–332.
15.
Kiss A, Palkovits M, Skirboll LR: Light microscopic triple-colored immunohistochemical staining on the same vibratome section using the avidin-biotin-peroxidase complex technique. Histochemistry 1988;88:353–356.
16.
Kaneko M, Hiroshige T, Shinsako J, Dallman MF: Diurnal changes in amplification of hormone rhythms in the adrenocortical system. Am J Physiol 1980;239:R309–R316.
17.
Ježová D, Kvetňanský R, Kovácz K, Opršalová Z, Vigaš M, Makara GB: Insulin-induced hypoglycemia activates the release of adrenocorticotropin predominantly via central and propranolol insensitive mechanisms. Endocrinology 1987;120:409–415.
18.
Ježová D, Guillaume V, Juránková E, Carayon P, Oliver C: Studies of the physiological role of ANF in ACTH regulation. Endocr Regul 1994;28:163–169.
19.
Dunnett CW: A multiple comparison procedure for comparing several treatments with a control. J Am Stat Assoc 1955;50:1096–1121.
20.
Dunn OJ: Multiple comparisons among means. J Am Stat Assoc 1976;56:52–59.
21.
Maiter D, Underwood LE, Martin JB, Koenig JI: Neonatal treatment with monosodium glutamate: Effects of prolonged growth hormone (GH)-releasing hormone deficiency on pulsatile GH secretion and growth in female rats. Endocrinology 1991;128:1100–1106.
22.
Slama A, Bluet-Pajot MT, Mounier F, Videau C, Kordon C, Epelbaum J: 125I-Somatostatin-labeled cells in the anterior arcuate nucleus mediate somatostatin effects on growth hormone but not prolactin secretion. Neuroendocrinology 1993;58:178–184.
23.
Sasaki F, Kawai T, Ohta M: Immunohistochemical evidence of neurons with GHRH or LHRH in the arcuate nucleus of male mice and their possible role in the postnatal development of adenohypophysial cells. Anat Rec 1994;240:255–260.
24.
Bodnar RJ, Abrams GM, Zimmerman EA, Krieger DT, Nicholson G, Kizer JS: Neonatal monosodium glutamate: Effects upon analgesic responsivity and immunocytochemical ACTH/β-lipotropin. Neuroendocrinology 1980;30:280–284.
25.
Johnston CA, Negro-Vilar A: Neurotoxin effects on oxytocin, vasopressin and somatostatin in discrete rat brain areas. Peptides 1986;7:749–753.
26.
Jessop DS, Chowdrey HS, Biswas S, Lightman SL: Substance P and substance K in the rat hypothalamus following monosodium glutamate lesions of the arcuate nucleus. Neuropeptides 1991;18:165–170.
27.
Miyabo S, Ooya E, Yamamura I, Hayashi S: Ontogeny of circadian corticosterone rhythm in rats treated with monosodium glutamate neonatally. Brain Res 1982;248:341–345.
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