Hypothalamo-Pituitary-Adrenal Axis Sensitization after Chronic Salt Loading

Abstract

Hypothalamic parvocellular vasopressin (VP) and corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) are major secretagogues of corticotropin (ACTH), and central plasticity including their alteration is closely related to hypothalamic-pituitary-adrenal (HPA) axis modulation. Chronic hyperosmotic stress caused by 2% salt lodaing has been known to alter VP and CRH expression. We recently reported that rehydration, a recovery stage from salt loading, induced a prolonged increase in parvocellular VP mRNA expression and suggested that rehydration can modulate HPA axis function without obvious external stress. In the present study, we examined hypothalamic VP and CRH mRNA expression and their responsiveness to acute immobilization stress in control, salt-loaded and rehydrated animals, in order to clarify the precise mechanism of HPA axis regulation during rehydration. The results were further compared with plasma corticosterone and ACTH levels. Plasma corticosterone decreased during salt loading, whereas it increased during rehydration at 1 week. Basal ACTH concentration increased in 1-week-rehydrated animals, with enhanced responsiveness to the acute immobilization stress. In the hypothalamic parvocellular PVN, basal CRH mRNA levels also decreased during salt loading and increased during rehydration. Basal VP mRNA was up-regulated during both salt loading and rehydration. VP mRNA responded to additional acute stress during salt loading and rehydration, but CRH mRNA did not. These results indicate that the HPA axis activity of parvocellular neurons is still altered at 1 week of rehydration and that VP plays a dominant role in regulating ACTH release in response to acute stress. This rehydration stage may thus be a good model for analysis of post-stress sensitization of the HPA axis.

Hydration state controls stress responsiveness and social behavior

“…Because hydro-electrolyte imbalance affects most physiological processes, it was unexpected that hypernatremia would attenuate ACTH and CORT release due to psychogenic stress. Reduced ACTH implies a central inhibition of the HPA axis, and consistent with this, chronic salt loading decreases nonstressed levels of plasma ACTH and corticotrophin-releasing hormone (CRH) within the parvocellular PVN (Lightman and Young, 1987) and reduces elevations in ACTH and CRH after immobilization stress (Amaya et al, 2001). …”

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].…”

Relaxin-3/INSL7 Regulates the Stress-response System in the Rat Hypothalamus

“…Trunk bloods were collected in chilled plastic tubes containing EDTA, and samples were centrifuged and the plasma extracted (Amaya et al 2001). Plasma ACTH concentration was determined using the ACTH radioimmunoassay kit (Mitsubishi Chemicals, Tokyo, Japan).…”