Following its discovery 20 years ago, corticotropin-releasing hormone (CRH) has been postulated to mediate both hormonal and behavioural responses to stressors. Here, we characterize and describe a behavioural role for the murine gene, UcnIII, which encodes a recently discovered CRH-related neuropeptide, urocortin III. We found that mouse UcnIII is expressed predominantly in regions of the brain known to be involved in stress-related behaviours, and its expression in the hypothalamus increases following restraint. In addition, we found that intracerebroventricular administration of mUcnIII stimulates behaviours that are associated with reduced anxiety, including exploration of an open field and decreased latency to enter the lit compartment of a dark-light chamber, but has no effect on the elevated-plus maze. Finally, we found that mUcnIII does not exert any effects on the hormonal stress response. Based upon our findings, UcnIII may be an endogenous brain neuropeptide that is modulated by stress and stimulates behaviours associated with reduced anxiety. In this capacity, UcnIII may attenuate stress-related behaviours, which may be useful both to help cope with stressful situations as well as to avoid pathology associated with excessive reaction to stressors.

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because of the Cushingoid appearance, with the characteristic features of central obesity, moon face, skin atrophy, purple striae and buffalo hump, and the clinical criteria are clear, a debate exists in the literature over the biochemical diagnosis of this disease [3]. Recently, the diagnostic criteria for Cushing's disease have been reported by the Ministry of Health, Labour, and Welfare of Japan [4]. In the guideline, the following endocrinological findings were considered as diagnostic criteria: 1) The presence of a Cushingoid appearance; 2) Evidence of autonomic or abnormal secretion of ACTH, such as (a) normal-high ACTH and cortisol levels, and (b) high levels of urinary excretion of free cortisol; 3) Screening tests show (a) incomplete suppression of cortisol (> 5 µg/dl) by a lowdose (0.5 mg) overnight dexamethasone suppression test (DST), (b) high cortisol levels (> 5 µg/dl) during night time sleeping, and (c) response of plasma ACTH levels to the desmopressin (DDAVP) test; 4) The dif- Abstract. We evaluated the usefulness and accuracy of diagnostic tests for adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, based on our experience of 88 cases, including 73 cases with Cushing's disease, and 15 cases with ectopic ACTH syndrome (EAS). In our study, 0.5 mg of dexamethasone failed to suppress the morning cortisol secretion in 100% of cases with Cushing's disease and EAS. Plasma ACTH levels were significantly increased by desmopressin (DDAVP) in 86% of cases with Cushing's disease, especially in microadenomas (90%), while these levels were not affected in normal subjects. In EAS, 44% responded to DDAVP. Plasma ACTH levels were increased in response to the human corticotropin-releasing hormone (CRH) test in 100% of microadenomas and 73% of macroadenomas with Cushing's disease, but only in 27% of cases with EAS. A high dose (8 mg) of dexamethasone suppressed the morning cortisol secretion in 89% of microadenomas with Cushing's disease, and in 82% of all cases with Cushing's disease, while it did in only 20% of cases with EAS. Taken together, the 0.5 mg dexamethasone suppression test (DST) and DDAVP test are considerably useful for the screening of ACTH-dependent Cushing's syndrome. The CRH test and 8 mg DST would be effective for the diagnosis of Cushing's diseases, because our study shows a sensitivity of 81% in cases with Cushing's disease when these tests are considered together. These data were submitted to prepare the diagnostic criteria for Cushing's disease, suggested by the working group of the Ministry of Health, Labour, and Welfare of Japan.