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

Abstract

Urocortin II (Ucn II) is a novel corticotropin-releasing hormone (CRH)-related peptide discovered as a selective agonist for type-2 CRH receptor. In the rat or mouse brain, Ucn II mRNA shows weak expression mainly in the hypothalamic paraventricular nucleus (PVN) and the locus coeruleus (LC). Understanding the regulation of Ucn II mRNA expression under varying conditions provides new insights into central stress response. We examined expression of Ucn II mRNA in the PVN and LC following immobilization stress, water deprivation, and adrenalectomy. Rats subjected to immobilization stress exhibited a dramatic induction of Ucn II mRNA expression in the parvocellular part of the PVN at the end of 2 h of immobilization. In contrast, water deprivation for 3 days induced Ucn II mRNA expression mainly in the magnocellular part of the PVN. Although water-deprived rats showed a marked decrease in their food intake, pair-fed rats failed to alter PVN Ucn II mRNA expression, suggesting that osmotic stimuli per se, but not reduced food consumption during water deprivation, caused Ucn II mRNA induction in the magnocellular part of the PVN. Adrenalectomized rats failed to show an increase in Ucn II mRNA in the PVN when compared to sham-operated rats. Double-label in situ hybridization revealed colocalization of Ucn II mRNA in approximately 45% of the CRH mRNA-expressing cells in the parvocellular part of the PVN following immobilization, or colocalization in most of the vasopressin mRNA-expressing cells in the magnocellular part of the PVN following water deprivation. In the LC, no induction of Ucn II mRNA was observed in any of the three experimental conditions, indicating that the regulation of Ucn II mRNA expression was site-specific. The results show a stressor-specific regulation of Ucn II mRNA expression in the PVN and raise the possibility that Ucn II mRNA plays a modulatory role in stress-induced alteration of anterior and posterior pituitary function, depending on the type of stress.

Urocortin 2-Deficient Mice Exhibit Gender-Specific Alterations in Circadian Hypothalamus–Pituitary–Adrenal Axis and Depressive-Like Behavior

“…Rodents normally exhibit proportionally more drinking during nocturnal than diurnal phases in relation to osmotic challenges, such as feeding (Johnson and Johnson, 1990a,b;Johnson et al, 2003;Zorrilla et al, 2005). As noted above, the colocalization of Ucn-2 and AVP in the magnocellular neurons of the PVN, its regulation by water deprivation (Tanaka et al, 2003), and the increase expression of AVP in the PVN and SON nuclei of the female Ucn-2-deficient mice may suggest a possible role for Ucn-2 in modulating fluid intake under specific osmotic challenges. Because CRFR2 is expressed in the PVN, Ucn-2 may regulate AVP expression or secretion in an autocrine or/and paracrine manner in the magnocellular PVN.…”

“…Ucn-2 is expressed by several hypothalamic nuclei, with highest levels of expression in the magnocellular neurons of the PVN . A recent study demonstrated a strong induction of Ucn-2 mRNA expression in the parvocellular region of the PVN after immobilization stress and dramatic Ucn-2 mRNA expression in the magnocellular division of the PVN after water deprivation (Tanaka et al, 2003). Using doublelabel in situ hybridization, Tanaka et al showed that Ucn-2 is colocalized with ϳ45% of CRF-expressing cells in the parvocellular part of the PVN and with most of the AVP neurons in the magnocellular part of the PVN after immobilization and water deprivation paradigms, respectively.…”

“…Pronounced sex differences exist in both stress and circadian-dependent activation, whereby females exhibit a greater magnitude and duration of HPA response to stressors and higher plasma concentration of ACTH and corticosterone throughout the daily rhythms with pronounced differences at the peak of the circadian rhythm (for review, see Rhodes and Rubin, 1999;Kudielka and Kirschbaum, 2005). CRF and AVP were proposed as the principal neuronal signals controlling diurnal ACTH and glucocorticoid rhythms (Patchev and Almeida, 1998;Tanaka et al, 2003). Ucn-2 is expressed by several hypothalamic nuclei, with highest levels of expression in the magnocellular neurons of the PVN .…”

“…5c), so changes were reflected in a blunting of the rhythm of the water-to-food ratio in female Ucn-2 mutant mice (Fig. 5e,f ), in which rodents normally exhibit proportionally more drinking during nocturnal than diurnal phases in relation to osmotic challenges, such as feeding (Patchev and Almeida, 1998;Tanaka et al, 2003;Kudielka and Kirschbaum, 2005;Zorrilla et al, 2005).…”

Estrogens downregulate urocortin 2 expression in rat uterus

“…Others and we previously demonstrated that Ucn2 is expressed in both the brain and peripheral tissues, including the lung, adrenal, uterus, ovary, and testis (Hsu & Hsueh 2001, Yamauchi et al 2005, Lee et al 2011. It has been reported that expression of Ucn2 mRNA in various tissues is controlled by stress, inflammation, and hypoxia (Tanaka et al 2003, Tao et al 2006, Chang et al 2007, Buhler et al 2009, Imperatore et al 2010, Nemoto et al 2010 and that factors involved in the regulation of Ucn2 mRNA expression are CRF, glucocorticoids, and endotoxins (Chen et al 2003(Chen et al , 2004mechanisms of Ucn2 expression in reproductive organs are not well understood.…”