Hyperkalemia in both surgically and medically treated patients with primary aldosteronism.

Hyperkalemia is an important complication of adrenalectomy for patients with primary aldosteronism (PA). The frequency of hyperkalemia after medication using mineralocorticoid receptor antagonists (MRAs) for PA is unclear. The aim of this study is to investigate the frequency and the risk factors of hyperkalemia after surgery and medication for PA. The data of 376 patients with PA registered in a multicentre-collaborative study in Japan, including surgically treated patients (group A; n=142) and medically treated patients with MRAs (group B; n=234) were studied. The prevalence of hyperkalemic patients (serum potassium >5.0 mEq l-1) after treatment was higher in group A than group B (9.9 vs 3.8%, P<0.01). At diagnosis, the hyperkalemic patients were older and had a poorer renal function than the non-hyperkalemic patients in both groups (P<0.05). The hyperkalemic patients had severer PA in group A and milder PA in group B. The independent risk factor by a logistic regression analysis was only age in both groups. After treatment, the percentages of patients withdrawing antihypertensive drugs and the normalization of aldosterone renin ratio were not different between hyperkalemic and non-hyperkalemic patients in group A. The type and dose of MRAs and the combination of other antihypertensive drugs were not different between hyperkalemic and non-hyperkalemic patients in group B. In conclusion, the potential occurrence of hyperkalemia should be considered after medical as well as surgical treatment for PA, especially in patients with older age (>60 years) and impaired renal function (estimated glomerular filtration rate <70 ml min-1 per 1.73 m2) at diagnosis.

Significance of adrenal computed tomography in predicting laterality and indicating adrenal vein sampling in primary aldosteronism.

Although laterality assessed by computed tomography (CT) in primary aldosteronism (PA) is not always concordant with that assessed by adrenal vein sampling (AVS), it is unclear whether all patients diagnosed with PA should undergo AVS for subtype classification. The aim of the current study was to investigate the accuracy of CT in subtype classification and to develop a prediction score for bilateral subtype in patients without adrenal tumour. As part of the WAVES-J study, 393 patients with PA were analysed. Subtyping using CT was concordant with that using AVS in 68% (269/393) of patients in the total sample, and in 38% (68/156) of patients with unilateral tumours, 56% (5/9) of patients with bilateral tumours and 89% (204/228) of patients without tumour. In patients without tumour, female gender, plasma aldosterone concentration (pg ml-1) to plasma renin activity ratio ⩽550 and serum potassium ⩾3.8 mEq l-1 were shown to be independent predictors for bilateral subtype. A prediction score based on these three variables was constructed with one point attributed to each variable. A score of three points had 29% sensitivity and 96% specificity in a receiver operating characteristic curve analysis. The results suggest that although CT is not sufficiently accurate for subtype classification in patients with adrenal tumours, it is sufficient to determine bilateral subtype in patients without tumour. Moreover, using our clinical prediction score in patients without tumour could be useful in determining the necessity of AVS for subtype classification.

Comparison of coronary heart disease risk among four diagnostic definitions of metabolic syndrome.

PURPOSE: Metabolic syndrome (MetS) is now well known as one of the major risk factors for coronary heart disease (CHD). Currently, there are several methods used to define MetS. The aim of this study was to determine to what extent current MetS definition reflects CHD risk using the probability of CHD in 10 years based on Framingham risk score algorithms. METHODS: A total of 7575 adults, aged 16-93 years (2532 men and 5043 women), were recruited. We conducted a cross-sectional health survey in China using MetS criteria from four different definitions: modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF), Chinese and Japanese. RESULTS: Differences in the prevalence of MetS by each definition were small in males (22.9-25.9 %), whereas in females, MetS was three times more prevalent using the IDF definition (29.1 %) versus the Japanese definition (9.7 %). Framingham risk scores in participants with MetS were significantly higher than in those without MetS by all definition criteria (p < 0.001). The CHD risk scores for participants with MetS by each definition showed similar values in males (range 11.5-12.1 %) with no significant differences among definitions. Conversely, in females with MetS the risk score for CHD was low (range 3.5-4.3 %) by each MetS definition. CONCLUSIONS: These findings suggest that further studies are required to establish appropriate criteria of MetS in females.

Amoeba-inspired nanoarchitectonic computing implemented using electrical Brownian ratchets.

In this study, we extracted the essential spatiotemporal dynamics that allow an amoeboid organism to solve a computationally demanding problem and adapt to its environment, thereby proposing a nature-inspired nanoarchitectonic computing system, which we implemented using a network of nanowire devices called 'electrical Brownian ratchets (EBRs)'. By utilizing the fluctuations generated from thermal energy in nanowire devices, we used our system to solve the satisfiability problem, which is a highly complex combinatorial problem related to a wide variety of practical applications. We evaluated the dependency of the solution search speed on its exploration parameter, which characterizes the fluctuation intensity of EBRs, using a simulation model of our system called 'AmoebaSAT-Brownian'. We found that AmoebaSAT-Brownian enhanced the solution searching speed dramatically when we imposed some constraints on the fluctuations in its time series and it outperformed a well-known stochastic local search method. These results suggest a new computing paradigm, which may allow high-speed problem solving to be implemented by interacting nanoscale devices with low power consumption.

Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline

"OBJECTIVE: The aim was to formulate clinical practice guidelines for pheochromocytoma and paraganglioma (PPGL). PARTICIPANTS: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), seven experts in the field, and a methodologist. The authors received no corporate funding or remuneration. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, European Society of Endocrinology, and Americal Association for Clinical Chemistry reviewed drafts of the guidelines. CONCLUSIONS: The Task Force recommends that initial biochemical testing for PPGLs should include measurements of plasma free or urinary fractionated metanephrines. Consideration should be given to preanalytical factors leading to false-positive or false-negative results. All positive results require follow-up. Computed tomography is suggested for initial imaging, but magnetic resonance is a better option in patients with metastatic disease or when radiation exposure must be limited. (123)I-metaiodobenzylguanidine scintigraphy is a useful imaging modality for metastatic PPGLs. We recommend consideration of genetic testing in all patients, with testing by accredited laboratories. Patients with paraganglioma should be tested for SDHx mutations, and those with metastatic disease for SDHB mutations. All patients with functional PPGLs should undergo preoperative blockade to prevent perioperative complications. Preparation should include a high-sodium diet and fluid intake to prevent postoperative hypotension. We recommend minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas. Partial adrenalectomy is an option for selected patients. Lifelong follow-up is suggested to detect recurrent or metastatic disease. We suggest personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes."

A subtype prediction score for primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Although adrenal venous sampling (AVS) is recommended as the gold standard procedure for subtype classification in PA, it is a specialized technique with limited availability. The objective of this study was to develop a scoring system that predicted PA subtype using clinical characteristics. Seventy-one patients with PA were studied. The subjects were diagnosed as having either unilateral (n=32) or bilateral disease (n=39) based on AVS, surgery and/or the postoperative clinical course. Variables associated with laterality in the univariate analysis were entered into multivariable logistic regression models and the regression coefficients were used to construct a subtype prediction score. The diagnostic significance of the score was then evaluated using receiver operating characteristic (ROC) curve analysis. The subtype prediction score was calculated as follows: serum potassium ⩽3.4 mEq l(-1), 2 points; plasma aldosterone concentration ⩾165 pg ml(-1), 3 points; and aldosterone to renin ratio ⩾1000 in a post-captopril challenge test (plasma renin activity in ng ml(-1) h(-1)), 3 points. ROC curve analysis for the ability to discriminate between unilateral and bilateral PA showed that a score of 5 points had 75% sensitivity and 95% specificity, and a score of 3 points had a sensitivity of 97% and a specificity of 59%. The area under the ROC curve was 0.920 (95% confidence interval, 0.859-0.979). Our subtype prediction score could discriminate between unilateral and bilateral PA and is useful for selecting patients who should undergo AVS before surgery.

SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis.

We have previously demonstrated that Sox17 expression is prominent at developmental stages corresponding to oligodendrocyte progenitor cell (OPC) cycle exit and onset of differentiation, and that Sox17 promotes initiation of OPC differentiation. In this study, we examined Sox17 expression and regulation under pathological conditions, particularly in two animal models of demyelination/remyelination and in post-mortem multiple sclerosis (MS) brain lesions. We found that the number of Sox17 expressing cells was significantly increased in lysolecithin (LPC)-induced lesions of the mouse spinal cord between 7 and 30 days post-injection, as compared with controls. Sox17 immunoreactivity was predominantly detected in Olig2(+) and CC1(+) oligodendrocytes and rarely in NG2(+) OPCs. The highest density of Sox17(+) oligodendrocytes was observed at 2 weeks after LPC injection, coinciding with OPC differentiation. Consistent with these findings, in cuprizone-treated mice, Sox17 expression was highest in newly generated and in maturing CC1(+) oligodendrocytes, but low in NG2(+) OPCs during the demyelination and remyelination phases. In MS tissue, Sox17 was primarily detected in actively demyelinating lesions and periplaque white matter. Sox17 immunoreactivity was co-localized with NOGO-A+ post-mitotic oligodendrocytes both in active MS lesions and periplaque white matter. Taken together, our data: (i) demonstrate that Sox17 expression is highest in newly generated oligodendrocytes under pathological conditions and could be used as a marker of oligodendrocyte regeneration, and (ii) are suggestive of Sox17 playing a critical role in oligodendrocyte differentiation and lesion repair.

In situ real-time monitoring of changes in the surface roughness during nonadiabatic optical near-field etching.

We performed in situ real-time monitoring of the change in surface roughness during self-organized optical near-field etching. During near-field etching of a silica substrate, we detected the scattered light intensity from a continuum wave (CW) laser (lambda = 633 nm) in addition to the etching CW laser (lambda = 532 nm) light source. We discovered that near-field etching not only decreases surface roughness, but also increases the number of scatterers, as was confirmed by analyzing the AFM image. These approaches provide optimization criteria for the etching parameter and hence for further decreases in surface roughness.

Hydrogen sulfide as a novel mediator for pancreatic pain in rodents.

OBJECTIVE: Hydrogen sulfide (H(2)S) is formed from l-cysteine by multiple enzymes including cystathionine-gamma-lyase (CSE) in mammals, and plays various roles in health and disease. Recently, a pronociceptive role for H(2)S in the processing of somatic pain was identified. Here, the involvement of H(2)S in pancreatic pain is examined. METHODS: Anaesthetised rats or mice received an injection of NaHS, a donor for H(2)S, or capsaicin into the pancreatic duct, and the expression of spinal Fos protein was detected by immunohistochemistry. Pancreatitis was created by 6 hourly doses of caerulein in unanaesthetised mice, and pancreatitis-related allodynia/hyperalgesia was evaluated using von Frey hairs. CSE activity and protein levels in pancreatic tissues were measured using the colorimetric method and western blotting, respectively. RESULTS: Either NaHS or capsaicin induced the expression of Fos protein in the superficial layers of the T8 and T9 spinal dorsal horn of rats or mice. The induction of Fos by NaHS but not capsaicin was abolished by mibefradil, a T-type Ca(2+) channel blocker. In conscious mice, repeated doses of caerulein produced pancreatitis accompanied by abdominal allodynia/hyperalgesia. Pretreatment with an inhibitor of CSE prevented the allodynia/hyperalgesia, but not the pancreatitis. A single dose of mibefradil reversed the established pancreatitis-related allodynia/hyperalgesia. Either the activity or protein expression of pancreatic CSE increased after the development of caerulein-induced pancreatitis in mice. CONCLUSIONS: The data suggest that pancreatic NaHS/H(2)S most probably targets T-type Ca(2+) channels, leading to nociception, and that endogenous H(2)S produced by CSE and possibly T-type Ca(2+) channels are involved in pancreatitis-related pain.

Generating small-scale structures from large-scale ones via optical near-field interactions.

Optical near-fields, which appear in the vicinity of structures when irradiated with light, exhibit a hierarchical nature, meaning that the degree of localization of optical near-fields at a given point is related to the scale of the structure involved in this process. Therefore, if we could make optically induced fabrication processes selectively localized in the near-field region, we could generate a smaller-scale structure even from a larger-scale one via optical near-field interactions. We demonstrate the theoretical basis of this with an angular spectrum analysis of optical near-fields. We also experimentally demonstrate such principles by using ZnO nanoneedles fabricated through metal-organic vapor phase epitaxy (MOVPE) followed by a photo-induced MOVPE procedure where smaller-scale generated structures were clearly observed with the help of light irradiation. We also observed that the generated fine structures followed a power-law distribution, indicating that fractal structures emerged via optical near-field interactions.

Increased expression of renin in chronic allograft nephropathy.

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of renal transplant failure in the first decade posttransplant. The precise pathogenetic mechanism for CAN is not completely understood. A possible role of renin-angiotensin system for CAN has been suggested through clinical observations that angiotensin-converting enzyme inhibition and angiotensin II receptor blockers prevent CAN. METHODS: Distribution of renin-positive cells in allograft biopsy specimens was examined immunohistochemically in 23 renal transplant recipients diagnosed with CAN Biopsy specimens obtained from seven recipients with stable renal function were examined as controls. Histologic evaluation was performed based on the Banff 97 classification. RESULTS: Renin-positive cells were found in the juxtaglomerular apparatus (JGA) adjoining the afferent arterioles in both groups. When the number of renin-positive cells in JGA was defined as a renin index, it was significantly higher in the CAN than the control group (P = .007). There was no significant difference in age, interval between transplantation and biopsy, and blood pressure between groups. Only a significantly higher serum creatinine was found in the CAN group. CONCLUSIONS: The increased renin-positive cells in JGA suggest a significant role of the intrarenal renin-angiotensin system activation in the development of CAN.

Development of a magnetizing stage for in situ observations with electron holography and Lorentz microscopy.

A magnetizing stage, by which approximately horizontal magnetic fields can be applied to thin-foiled specimens, has been developed so that magnetization process can be observed in situ with electron holography and Lorentz microscopy. It is possible to apply magnetic field up to 200 Oe without serious image distortion by utilizing the magnetizing stage, beam-deflection-back coils and a magnetically shielded objective lens. The devised system can be used to studies of magnetization processes in many soft magnets.

Molecular identification and immunohistochemical localization of atrial natriuretic peptide in the heart of the dromedary camel (Camelus dromedarius).

Atrial and B-type natriuretic peptide (ANP and BNP) are cardiac hormones synthesized and secreted by the myoendocrine cells of the heart. They exert potent actions on body fluid balance. Since various body organs including the heart are under high physiological stress during water and food deprivation in the desert nomads, we intended to perform molecular biological and histological studies of ANP in the heart of the dromedary camel Camelus dromedarius. Initially, we isolated cDNAs encoding ANP from the atrium and BNP from the atrium and ventricle of the dromedary camel. Putative mature ANP, deduced from the cDNA sequence, was identical to that of human and pig ANP, but the putative mature BNP was more diverse and was most similar to pig BNP (94% identity). Thus, we used antisera raised against human ANP that did not cross-react with pig BNP in the subsequent immunohistochemical studies. The ANP-expressing myoendocrine cells are most concentrated in the right atrium, to a lesser extent in the left atrium, and almost absent in the left ventricle. The immuno-positive cells are scattered uniformly in each region and are characterized by the presence of immunoreactive granular deposits around the nucleus. The left atrium comprises some ramifications of conductive cells (Purkinje fibers), some of which also contained ANP-immunoreactive granules. At the electron microscopic level, myoendocrine cells possessed secretory granules primarily in the perinuclear zone and a well-developed Golgi apparatus. The present study is the first comprehensive report dealing with the molecular cloning and immunohistochemical localization of ANP in the heart of a desert dwelling mammal.

Inhibition of osteoclast formation by 3-methylcholanthrene, a ligand for arylhydrocarbon receptor: suppression of osteoclast differentiation factor in osteogenic cells.

We investigated the effects of 3-methylcholanthrene (3MC), a ligand for arylhydrocarbon receptor (AhR), on osteoclastogenesis. Osteoclast-like cells, in cocultures with mouse spleen cells and clonal osteogenic stromal ST2 cells, are formed from spleen cells by a combination of the receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) produced by ST2 cells in response to 1alpha,25(OH)(2) Vitamin D(3). 3MC dose-dependently inhibited the formation of mono- and multinuclear osteoclast-like cells. However, 3MC did not inhibit the formation of osteoclast-like cells from mouse spleen cells which was supported by the exogenous soluble RANKL and M-CSF. 3MC did not affect the formation of an actin ring and pits on slices of dentine by osteoclast-like cells, both of which are typical indices of osteoclast activity. These results suggest that 3MC affects osteoclast-supporting cells such as ST2 cells but not osteoclast precursor cells and mature osteoclastic cells. When we measured the expression levels of RANKL mRNA in ST2 cells, 3MC dose-dependently decreased the level of this mRNA. However, 3MC did not affect levels of mRNAs for osteoprotegerin (OPG), M-CSF, and the receptor of 1alpha,25(OH)(2) Vitamin D(3) in ST2 cells. Furthermore, soluble RANKL was able to counteract the inhibitory effect of 3MC on the formation of osteoclast-like cells. Our findings indicate that 3MC inhibits osteoclastogenesis via the inhibition of RANKL expression in osteoblastic cells.

Prooxidant action of gallic acid compounds: copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine in DNA.

Gallic acid and its alkylesters, polyphenolic compounds with antioxidative activity, acted as a prooxidant causing a copper-dependent DNA damage. Treatment of DNA from plasmid pBR322 and calf thymus with gallic acid plus copper ion caused strand scission and the formation of 8-hydroxy-2'-deoxyguanosine in DNA. Addition of catalase protected DNA from the gallic acid/copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine, indicating that hydroxyl radical may participate in the DNA damage. Ethyl-, propyl- and butylgallates showed only a little DNA damage. Octyl- and laurylgallates caused negligible damage of DNA. DNA strand breaks and formation of 8-hydroxy-2'-deoxyguanosine were closely related to the reduction of copper by gallate compounds. These results imply that cuprous ion reduced by gallate derivatives may play a key role in the oxidative cleavage of DNA and the formation of base adduct. The cytotoxic effect of gallate compounds can be explained by their prooxidant action dependent on the reducing activity.

Angiotensin II type 2 receptor mediates vascular smooth muscle cell apoptosis in cystic medial degeneration associated with Marfan's syndrome.

BACKGROUND: Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan's syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD. On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). METHODS AND RESULTS: To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (n=10) and control aortas (n=12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (P<0.01) and AT2R expression was significantly increased (P<0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (P<0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (P<0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients. CONCLUSIONS: Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD.

Autonomy of cortisol secretion in clinically silent adrenal incidentaloma.

Recent progress in non-invasive imaging techniques have resulted in an increasing frequency of adrenal incidentaloma discovery. In addition, even clinically silent adrenal tumor has been suggested to possess a subtle production of adrenal hormones. The aim of the study was to ascertain the autonomy of cortisol production in clinically silent adrenocortical incidentaloma. We investigated the hypothalamic-pituitary-adrenal axis in 38 patients with adrenal incidentaloma. Basal plasma cortisol level was reproducibly within normal range in all the patients with adrenal incidentaloma, but was also normal in half of the Cushing's syndrome cases studied. Eighteen of 38 patients showed plasma cortisol above 3 microg/dl after 1 mg dexamethasone (Dex) and above 1 microg/dl after 8 mg Dex, respectively, and were defined as preclinical Cushing's syndrome. These patients were subjected to further evaluation of the autonomy of cortisol production. The incidence of positive findings indicating autonomy of cortisol secretion was as follows: suppressed basal plasma ACTH level in 44%, loss of normal diurnal rhythm in 79%, lack of ACTH response to CRF in 35%, decreased plasma DHEA-S level in 28%, significant laterality of 131I-adosterol uptake in 75%, atrophy of the contralateral side of the adrenal on CT scan in 6%, and histological atrophy of the adjacent adrenal cortex in 56%, respectively. The endocrine feature relevant to the hypothalamic-pituitary-adrenal axis varied from patient to patient, ranging from the non-functioning adrenal adenoma to Cushing's syndrome. In addition, the results of each test did not coincide with others in each patient. These results clearly demonstrated that the incidence of autonomy of cortisol production in the clinically silent adrenal incidentaloma is not infrequent, showing significant diversity. Systemic evaluation of the hypothalamic-pituitary-adrenal axis before adrenal surgery is warranted for an appropriate glucocorticoid replacement after adrenal surgery.

Dynamic computer tomography is useful in the differential diagnosis of juxtaglomerular cell tumor and renal cell carcinoma.

We compared dynamic computer tomographic CT images of 3 cases of juxtaglomerular (JG) cell tumor with those of 8 cases of renal cell carcinoma (RCC). The JG cell tumor was visualized as a low- to high-density area in case 1, a low-density area in case 2, and a low- to iso-density area in case 3 before contrast enhancement. None of the JG cell tumors were stained during the early phase (1 min), but all were stained moderately during the late phase (5 min) after contrast enhancement. Although all cases of RCC were visualized as a low- to iso-density area before contrast enhancement, they were intensely stained during the early phase with significant washout during the late phase. The present results suggest that the dynamic CT scan is useful in the differential diagnosis of the JG cell tumor and RCC.

Expression of corticotropin-releasing hormone type 1 receptor in paraventricular nucleus after acute stress.

We have previously proposed the existence of ultrashort loop-positive feedback regulation of corticotropin-releasing hormone (CRH) in the hypothalamus. To gain a better understanding of this effect, we performed double-label in situ hybridization to identify the neurons in the paraventricular nucleus (PVN) that express CRH type 1 receptor (CRH-R1) following stress. We also conducted immunohistochemistry to determine whether CRH-R1 mRNA was translated to CRH-R1 protein in the PVN. Thirty-minute restraint stress given to male Wistar rats increased c-fos mRNA expression primarily in the CRH-producing neurons of the parvocellular PVN. Small numbers of vasopressin and oxytoxin-producing cells were also labeled by c-fos probes. Approximately 70% of CRH-R1 positive neurons exhibited CRH mRNA 2 h after the beginning of stress, while only a small percentage of the vasopressin and oxytocin-producing cells coexpressed CRH-R1 mRNA. CRH-R1 immunoreactivity, which was detected in the perikarya and fibers of PVN neurons, appeared to increase in response to stress, though this was not statistically significant. Pretreatment with a selective CRH-R1 antagonist, CP-154,526, significantly attenuated stress-induced corticotropin (ACTH) secretion as well as c-fos mRNA expression in the PVN. These results demonstrate that acute stress increases neuronal activation and CRH-R1 mRNA expression primarily in CRH-producing neurons of the parvocellular PVN, that CRH-R1 message is translated to CRH-R1 protein, and that PVN neurons are activated at least in part through CRH-R1 under acute stress. The data further support the possibility of feedback regulation of CRH itself in CRH-producing neurons.