Expression of Corticotropin Releasing Factor (CRF), Urocortin and CRF Type 1 Receptors in Hypothalamic‐Hypophyseal Systems Under Osmotic Stimulation

Abstract

The expression of corticotropin releasing factor (CRF) and urocortin in hypothalamic magnocellular neurones increases in response to osmotic challenge. To gain a better understanding of the physiological roles of CRF and urocortin in fluid homeostasis, CRF, urocortin and CRF type 1 receptor (CRFR-1) gene expression was examined in the hypothalamic-hypophyseal system usingin situ and double-label in situ hybridization following chronic salt loading. CRFR-1 expression was further examined by immunohistochemistry and receptor binding. Ingestion of hypertonic saline by Sprague-Dawley rats for 7 days induced CRF mRNA exclusively in the oxytocin neurones of the magnocellular paraventricular nucleus (PVN) and the supraoptic nucleus (SON), but induced CRFR-1 mRNA in both oxytocin and vasopressin-containing magnocellular neurones. Hypertonic saline treatment also increased urocortin mRNA expression in the PVN and the SON. In the SON, urocortin was localized to vasopressin and oxytocin neurones but was rarely seen in CRF-positive cells. Changes in CRFR-1 mRNA expression in magnocellular neurones by hypertonic saline treatment were accompanied by changes in CRFR-1 protein levels and receptor binding. Hypertonic saline treatment increased CRFR-1-like immunoreactivity in the magnocellular PVN and SON, and decreased it in the parvocellular PVN. CRF receptor binding in the PVN and SON was also increased in response to osmotic stimulation. Finally, hypertonic saline treatment increased CRFR-1 mRNA, CRFR-1-like immunoreactivity and CRF receptor binding in the intermediate pituitary. These results demonstrate that the increase in the expression of CRF and urocortin message in magnocellular neurones induced by salt loading is accompanied by an increase in CRF receptor levels and binding in the hypothalamus and intermediate pituitary. Thus, CRF and urocortin may exert modulatory effects locally within magnocellular neurones as well as at the pituitary gland in response to osmotic stimulation.

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

“…In contrast, osmotic stimuli such as hypertonic saline ingestion or water deprivation decreased CRH mRNA in the parvocellular PVN. Rather, hypertonic saline ingestion, but not water deprivation, induced CRH mRNA exclusively in the oxytocin neurons in the magnocellular part of the PVN [17, 18]. The present study demonstrated that Ucn II mRNA induction was observed in the parvocellular part or in the magnocellular part in the PVN following immobilization or water deprivation, respectively.…”

Human Urocortin 2, a Corticotropin-Releasing Factor (CRF)2Agonist, and Ovine CRF, a CRF1Agonist, Differentially Alter Feeding and Motor Activity

“…Analogously, many "specific" anorectics, including fenfluramine and lep- tin, reduce prandial drinking. Alternatively, hypodipsia might reflect a primary effect on drinking, either as independent regulation of body fluid homeostasis (possibly via CRF/ urocortin signaling elements in the supraoptic nucleus) (Van Pett et al, 2000;Imaki et al, 2001;Reyes et al, 2001) or as nonspecific, but coordinated, suppression of diverse appetitive behaviors. A better understanding of the functional significance of CRF/Ucn-induced hypodipsia will increase understanding of the significance of CRF receptor-mediated anorexia.…”

Physiology, pharmacology, and therapeutic relevance of urocortins in mammals: Ancient CRF paralogs

“…Accordingly, salt loading, dehydration and hypophysectomy increase Ucn-like-immunoreactivity in magnocellular SON and PVN neurons, whereas food deprivation decreases Ucn-like-immunoreactivity in the SON (studies in which the antibody specificity for Ucn 1 vs. Ucn 2 is uncertain) [100][101][102]. Specific increases in SON Ucn 1 mRNA expression also have been observed following salt loading [118]. Chronic osmotic stimulation (by salt loading or water deprivation) increases CRF 2 mRNA levels in the SON and magnocellular PVN, potentially increasing sensitivity to resident Ucns [8].…”