Lack of Decrease in Hypothalamic and Hippocampal Glucocorticoid Receptor mRNA during Starvation

Abstract

We have shown in a previous study that high corticosterone levels during repeated immobilization stress result in a reduction of glucocorticoid receptor (GR) mRNA in the hypothalamic paraventricular nucleus (PVN) and the hippocampus. The reduction of GR presumably accounts for loss of or decrease in glucocorticoid-negative feedback, and thus hyperfunction of the hypothalamic-pituitary-adrenocortical (HPA) axis persists during chronic stress. Starvation is a stress state in which the counterregulatory responses against the loss of food occur in the central nervous system. We explored the impact of starvation on the HPA axis, GR and mineralocorticoid receptor (MR) mRNAs in the hippocampus, the PVN, and the anterior pituitary (AP) of rats. Rats were starved for 4 days and sacrificed in the morning. Starved rats showed high levels of plasma corticosterone, whereas neither plasma corticotropin (ACTH), AP proopiomelanocortin (POMC) mRNA nor AP type-1 corticotropin-releasing hormone (CRH) receptor mRNA was altered in the starved rats. In the presence of high corticosterone, starvation resulted in a decrease in both CRH mRNA and type-1 CRH receptor mRNA in the PVN. Consistently, the starved rats did not show any changes in GR mRNA in the hippocampus (CA1-2, CA3, and dentate gyrus), the PVN or the AP despite the elevation of plasma corticosterone. A significant decrease in MR mRNA was seen in the dentate gyrus and the AP, but not in CA1–2, CA3 or PVN. The lack of reduction of GR may be one of the organism’s counterregulatory responses during starvation, which allows an intact glucocorticoid negative feedback, thereby resulting in decreased anorectic neuropeptide levels, namely CRH, in the PVN. The results also indicate that GR mRNA in the hippocampus and other brain regions is not solely regulated by circulating glucocorticoids. The mechanism underlying the regulation of GR mRNA in the central nervous system remains to be clarified.

Possible role of CRF peptides in burn-induced hypermetabolism

“…Pair-fed rats also exhibited increased plasma levels of CORT, but only in the day 3 group. This elevation in plasma CORT in food-deprived PF rats is consistent with reported elevation of the glucocorticoid in starved rats (Makino et al, 2001;Nazarloo et al, 2002), reflecting the activation of metabolic responses to starvation such as increased protein catabolism and gluconeogenesis.…”

Chronic Unpredictable Stress Exacerbates Lipopolysaccharide-Induced Activation of Nuclear Factor-κB in the Frontal Cortex and Hippocampus via Glucocorticoid Secretion

“…However, some hypotheses can be raised. First, there is a trend toward the proinflammatory effects being more likely in the face of highly elevated, chronic GC exposure and in brain regions most sensitive to the hormone (Abraham et al, 2000;Makino et al, 2001). The role of chronicity is important, because high-dose GCs are used therapeutically for inflammatory diseases such as arthritis, asthma, and multiple sclerosis.…”

Effect of Stress and Adrenalectomy on Urocortin II mRNA Expression in the Hypothalamic Paraventricular Nucleus of the Rat

“…Osmotic stimuli are often accompanied by reduced food intake [8], and food deprivation per se is known to induce similar neuropeptide changes (e.g. decreased CRH mRNA in the PVN) to those observed in osmotic stimuli [6, 7, 8, 9, 10, 11]. In order to distinguish the effects of osmotic stimuli from those of reduced food intake, we prepared 3 groups of rats: (1) control rats with free access to both food and water (n = 9); (2) rats subjected to water deprivation for 3 days with free access to food (WD group, n = 8), and (3) pair-fed rats which were allowed to eat the same amount of food as the water-deprived rats with free access to water (PF group, n = 8).…”

“…Many stressors, such as immobilization, augment CRH neuronal activity as indicated by an increase in CRH mRNA in the PVN; however, the degree of CRH secretion and pituitary-adrenocortical activation depends on the type, intensity, and/or duration of the stressor [5]. Conversely, some stressors such as starvation or water deprivation can suppress CRH mRNA expression in the parvocellular part of the PVN [6, 7, 8, 9, 10, 11]. In addition, adrenalectomy increases, while an administration of glucocorticoids decreases CRH mRNA in the PVN, indicating that CRH secretion in the PVN is under the negative feedback control of the glucocorticoids [4].…”