Foraging habitat and site selection do not affect feeding rates in European shags.

During feeding trips, central-place foragers make decisions on whether to feed at a single site, move to other sites and/or exploit different habitats. However, for many marine species, the lack of fine-resolution data on foraging behaviour and success has hampered our ability to test whether individuals follow predictions of the optimal foraging hypothesis. Here, we tested how benthic foraging habitat usage, time spent at feeding sites and probability of change of feeding sites affected feeding rates in European shags (Gulosus aristotelis) using time-depth-acceleration data loggers in 24 chick-rearing males. Foraging habitat (rocky or sandy) was identified from characteristic differences in dive patterns and body angle. Increase in body mass was estimated from changes in wing stroke frequency during flights. Bout feeding rate (increase in body mass per unit time of dive bout) did not differ between rocky and sandy habitats, or in relation to the order of dive bouts during trips. Bout feeding rates did not affect the duration of flight to the next feeding site or whether the bird switched habitat. However, the likelihood of a change in habitat increased with the number of dive bouts within a trip. Our findings that shags did not actively move further or switch habitats after they fed at sites of lower quality are in contrast to the predictions of optimal foraging theory. Instead, it would appear that birds feed probabilistically in habitats where prey capture rates vary as a result of differences in prey density and conspecific competition or facilitation.

At-Sea Habitat Use of Rhinoceros Auklets Breeding in the Shelf Region of Eastern Hokkaido.

At-sea habitat use of breeding seabirds is strongly influenced by marine environmental features that vary over space and time. The use of bio-loggers allows researchers to track fine-scale movements of seabirds and provides opportunities to identify the primary factors affecting their area use for foraging. Using GPS loggers, we tracked chick-rearing rhinoceros auklets (Cerorhinca monocerata), which are wing-propelled divers, at Daikoku Island, eastern Hokkaido, Japan. The central phase for foraging activity on birds' trips was determined using a multiple change points model. To examine environmental factors explaining the distribution of the foraging phase, a generalized additive model was used where sea surface temperature, chlorophyll a concentration, bathymetry, and distance from the colony were explanatory variables. To obtain information supporting the behavioral tracking, prey items in the bill-loads of adult auklets were collected. We found that auklets foraged over the continental shelf shallower than the 200-m isobath and that distance from the colony was related to the area use. Adult auklets predominately brought back age-0 chum salmon (Oncorhynchus keta), which was abundant in coastal waters along southeast Hokkaido during the study period. Our findings indicate that rhinoceros auklets rearing chicks, hence visiting nests frequently, on Daikoku Island can find suitable feeding grounds nearby.

Mapping the collision risk between two gull species and offshore wind turbines: Modelling and validation.

Promoting the use of renewable energy and conserving biodiversity are conflicting issues that need addressing. While the development of offshore wind facilities/turbines is accelerating, many seabirds have been exposed to collisions with wind turbines. We must identify high collision areas and avoid the construction of wind turbines in these spaces to reduce these conflicts. One solution is to develop useful finer scale sensitivity maps. In this study, we created a fine-scale map of collision risk by spatial modelling using information from bird flights at sea and explored the relative importance of each geographic variable relevant to the risk. Between 2016 and 2019, we collected 3D-location data from 117 black-tailed gulls (Larus crassirostris) of three colonies in two areas and 21 slaty-backed gulls (L. schistisagus) of four colonies in one area of northern Hokkaido, Japan. The spatial models that explain the occurrence of M-zone flight, which is the flight within the heights of high collision risk (20-140 m height), were constructed at a 1 km mesh using a random forest algorithm, a machine-learning tool. The model satisfactory predicted the spatial distribution of M-zone flights using geographic variables and species (correlation coefficient: 0.57-0.94), although data had some degrees of variation between species, years, colonies, and areas. Our model can be applied to other regions, as long as we have general topological information and the locations of colonies and harbors. The distance to the breeding colony and the nearest harbors were important, and the collision risk was 6-7 times higher within 15 km from the colonies and 5 km from harbors. Black-tailed gulls used different sites for foraging and commuting between years, whereas slaty-backed gulls used relatively consistent sites. These variations between species and among years suggest that collecting bird data over multiple years is necessary and effective for creating a generally applicable sensitivity map.

Differential Effects of Fkbp4 and Fkbp5 on Regulation of the Proopiomelanocortin Gene in Murine AtT-20 Corticotroph Cells.

The hypothalamic-pituitary-adrenal axis is stimulated in response to stress. When activated, it is suppressed by the negative feedback effect of glucocorticoids. Glucocorticoids directly inhibit proopiomelanocortin (Pomc) gene expression in the pituitary. Glucocorticoid signaling is mediated via glucocorticoid receptors, 11ß-hydroxysteroid dehydrogenases, and the FK506-binding immunophilins, Fkbp4 and Fkbp5. Fkbp4 and Fkbp5 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor, resulting in modulation of the glucocorticoid action. Here, we explored the regulation of Fkbp4 and Fkbp5 genes and their proteins with dexamethasone, a major synthetic glucocorticoid drug, in murine AtT-20 corticotroph cells. To elucidate further roles of Fkbp4 and Fkbp5, we examined their effects on Pomc mRNA levels in corticotroph cells. Dexamethasone decreased Pomc mRNA levels as well as Fkpb4 mRNA levels in mouse corticotroph cells. Dexamethasone tended to decrease Fkbp4 protein levels, while it increased Fkpb5 mRNA and its protein levels. The dexamethasone-induced decreases in Pomc mRNA levels were partially canceled by Fkbp4 knockdown. Alternatively, Pomc mRNA levels were further decreased by Fkbp5 knockdown. Thus, Fkbp4 contributes to the negative feedback of glucocorticoids, and Fkbp5 reduces the efficiency of the glucocorticoid effect on Pomc gene expression in pituitary corticotroph cells.

Attenuation imaging based on ultrasound technology for assessment of hepatic steatosis: A comparison with magnetic resonance imaging-determined proton density fat fraction.

AIM: A new method has recently been developed for diagnosing hepatic steatosis based on attenuation measurement using ultrasound. We investigated the ability of attenuation imaging (ATI) to detect steatosis that was identified by proton density fat fraction (PDFF) on magnetic resonance imaging (MRI) in patients with chronic liver disease. METHODS: A total of 119 patients with chronic liver disease (non-B, non-C) were analyzed. The relationship between ATI values and steatosis grades determined by PDFF was evaluated. Additionally, the diagnostic ability of ATI was evaluated using receiver operating characteristic curve analysis, and the correlation between ATI values and PDFF values was determined. RESULTS: The ATI values of steatosis grades 0, 1, 2, and 3 were 0.55, 0.61, 0.74, and 0.84 dB/cm/MHz, respectively (P < 0.001). There was a statistically significant trend of higher ATI values with higher steatosis grades (P < 0.001). The correlation coefficient (r) between PDFF values and ATI values was 0.70 (95% confidence interval [CI] 0.59-0.78; P < 0.001), corresponding to a strong relationship. The diagnostic ability of ATI for steatosis grades ≥1, ≥2, and 3, as determined by PDFF, were 0.81 (95% CI 0.73-0.89), 0.87 (95% CI 0.79-0.96), and 0.94 (95% CI 0.89-0.98), respectively. The r between PDFF values and ATI values was 0.49 (95% CI 0.31-0.63; P < 0.001) for patients with mild or no steatosis (grade ≤1), and 0.75 (95% CI 0.57-0.86; P < 0.001) for obese patients (body mass index ≥25 kg/m2 ). CONCLUSION: ATI values had an excellent diagnostic ability to detect hepatic steatosis.

Secondary oxalosis induced by xylitol concurrent with lithium-induced nephrogenic diabetes insipidus: a case report.

BACKGROUND: Xylitol is an approved food additive that is widely used as a sweetener in many manufactured products. It is also used in pharmaceuticals. Secondary oxalosis resulting from high dietary oxalate has been reported. However, reported cases of oxalosis following xylitol infusion are rare. CASE PRESENTATION: A 39-year-old man with a 16-year history of organic psychiatric disorder was hospitalized for a laparoscopic cholecystectomy because of cholecystolithiasis. He had been treated with several antipsychotics and mood stabilizers, including lithium. The patient had polyuria (> 4000 mL/day) and his serum sodium levels ranged from 150 to 160 mmol/L. Urine osmolality was 141 mOsm/L, while serum arginine vasopressin level was 6.4 pg/mL. The patient was diagnosed with nephrogenic diabetes insipidus (NDI), and lithium was gradually discontinued. Postoperative urine volumes increased further to a maximum of 10,000 mL/day, and up to 10,000 mL/day of 5% xylitol was administered. The patient's consciousness level declined and serum creatinine increased to 4.74 mg/dL. This was followed by coma and metabolic acidosis. After continuous venous hemodiafiltration, serum sodium improved to the upper 140 mmol/L range and serum creatinine decreased to 1.25 mg/dL at discharge. However, polyuria and polydipsia of approximately 4000 mL/day persisted. Renal biopsy showed oxalate crystals and decreased expression of aquaporin-2 (AQP2) in the renal tubules. Urinary AQP2 was undetected. The patient was discharged on day 82 after admission. CONCLUSIONS: Our patient was diagnosed with lithium-induced NDI and secondary oxalosis induced by excess xylitol infusion. NDI became apparent perioperatively because of fasting, and an overdose of xylitol infusion led to cerebrorenal oxalosis. Our patient received a maximum xylitol dose of 500 g/day and a total dose of 2925 g. Patients receiving lithium therapy must be closely monitored during the perioperative period, and rehydration therapy using xylitol infusion should be avoided in such cases.

Flight paths of seabirds soaring over the ocean surface enable measurement of fine-scale wind speed and direction.

Ocean surface winds are an essential factor in understanding the physical interactions between the atmosphere and the ocean. Surface winds measured by satellite scatterometers and buoys cover most of the global ocean; however, there are still spatial and temporal gaps and finer-scale variations of wind that may be overlooked, particularly in coastal areas. Here, we show that flight paths of soaring seabirds can be used to estimate fine-scale (every 5 min, ∼5 km) ocean surface winds. Fine-scale global positioning system (GPS) positional data revealed that soaring seabirds flew tortuously and ground speed fluctuated presumably due to tail winds and head winds. Taking advantage of the ground speed difference in relation to flight direction, we reliably estimated wind speed and direction experienced by the birds. These bird-based wind velocities were significantly correlated with wind velocities estimated by satellite-borne scatterometers. Furthermore, extensive travel distances and flight duration of the seabirds enabled a wide range of high-resolution wind observations, especially in coastal areas. Our study suggests that seabirds provide a platform from which to measure ocean surface winds, potentially complementing conventional wind measurements by covering spatial and temporal measurement gaps.

Global Monitoring of Persistent Organic Pollutants (POPs) Using Seabird Preen Gland Oil.

Situated at high positions on marine food webs, seabirds accumulate high concentrations of persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), and hexachlorocyclohexanes (HCHs). Our previous studies proposed the usefulness of seabirds preen gland oil as a nondestructive biomonitoring tool. The present study applied this approach to 154 adult birds of 24 species collected from 11 locations during 2005-2016 to demonstrate the utility of preen gland oil as a tool for global monitoring POPs, i.e., PCBs, DDTs, and HCHs. Concentrations of the POPs were higher in the Northern Hemisphere than in the Southern Hemisphere. In particular, ∑20PCBs and∑DDTs were highly concentrated in European shags (Phalacrocorax aristotelis) and Japanese cormorants (Phalacrocorax capillatus), explainable by a diet of benthic fishes. Higher concentrations of γ-HCH were detected in species from the polar regions, possibly reflecting the recent exposure and global distillation of ∑HCHs. We examined the relationship between age and POP concentrations in preen gland oil from 20 male European shags, aged 3-16 years old. Concentrations and compositions of POPs were not related to age. We also examined sex differences in the POP concentrations from 24 streaked shearwaters (Calonectris leucomelas) and did not detect a sex bias. These results underline the importance of the geographic concentration patterns and the dietary behavior as determinants species-specific POPs concentrations in preen gland oil.

European shags optimize their flight behavior according to wind conditions.

Aerodynamics results in two characteristic speeds of flying birds: the minimum power speed and the maximum range speed. The minimum power speed requires the lowest rate of energy expenditure per unit time to stay airborne and the maximum range speed maximizes air distance traveled per unit of energy consumed. Therefore, if birds aim to minimize the cost of transport under a range of wind conditions, they are predicted to fly at the maximum range speed. Furthermore, take-off is predicted to be strongly affected by wind speed and direction. To investigate the effect of wind conditions on take-off and cruising flight behavior, we equipped 14 European shags Phalacrocorax aristotelis with a back-mounted GPS logger to measure position and hence ground speed, and a neck-mounted accelerometer to record wing beat frequency and strength. Local wind conditions were recorded during the deployment period. Shags always took off into the wind regardless of their intended destination and take-off duration was correlated negatively with wind speed. We combined ground speed and direction during the cruising phase with wind speed and direction to estimate air speed and direction. Whilst ground speed was highly variable, air speed was comparatively stable, although it increased significantly during strong head winds, because of stronger wing beats. The increased air speeds in head winds suggest that birds fly at the maximum range speed, not at the minimum power speed. Our study demonstrates that European shags actively adjust their flight behavior to utilize wind power to minimize the costs of take-off and cruising flight.

Statistical integration of tracking and vessel survey data to incorporate life history differences in habitat models.

Habitat use is often examined at a species or population level, but patterns likely differ within a species, as a function of the sex, breeding colony, and current breeding status of individuals. Hence, within-species differences should be considered in habitat models when analyzing and predicting species distributions, such as predicted responses to expected climate change scenarios. Also, species' distribution data obtained by different methods (vessel-survey and individual tracking) are often analyzed separately rather than integrated to improve predictions. Here, we eventually fit generalized additive models for Streaked Shearwaters Calonectris leuconelas using tracking data from two different breeding colonies in the Northwestern Pacific and visual observer data collected during a research cruise off the coast of western Japan. The tracking-based models showed differences among patterns of relative density distribution as a function of life history category (colony, sex, and breeding conditions). The integrated tracking-based and vessel-based bird count model incorporated ecological states rather than predicting a single surface for the entire species. This study highlights both the importance of including ecological and life history data and integrating multiple data types (tag-based tracking and vessel count) when examining species-environment relationships, ultimately advancing the capabilities of species distribution models.

The jellyfish buffet: jellyfish enhance seabird foraging opportunities by concentrating prey.

High levels of jellyfish biomass have been reported in marine ecosystems around the world, but understanding of their ecological role remains in its infancy. Jellyfish are generally thought to have indirect negative impacts on higher trophic-level predators, through changes in lower trophic pathways. However, high densities of jellyfish in the water column may affect the foraging behaviour of marine predators more directly, and the effects may not always be negative. Here, we present novel observations of a diving seabird, the thick-billed murre, feeding on fish aggregating among the long tentacles of large jellyfish, by using small video loggers attached to the birds. We show that the birds encountered large jellyfish, Chrysaora melanaster, during most of their dives, commonly fed on fish associated with jellyfish, and appeared to specifically target jellyfish with a high number of fish aggregating in their tentacles, suggesting the use of jellyfish may provide significant energetic benefits to foraging murres. We conclude that jellyfish provide feeding opportunities for diving seabirds by concentrating forage fish, and that the impacts of jellyfish on marine ecosystems are more complex than previously anticipated and may be beneficial to seabirds.

Facilitated Leaching of Additive-Derived PBDEs from Plastic by Seabirds' Stomach Oil and Accumulation in Tissues.

Our previous study suggested the transfer of polybrominated diphenyl ether (PBDE) flame retardants from ingested plastics to seabirds' tissues. To understand how the PBDEs are transferred, we studied leaching from plastics into digestive fluids. We hypothesized that stomach oil, which is present in the digestive tract of birds in the order Procellariiformes, acts as an organic solvent, facilitating the leaching of hydrophobic chemicals. Pieces of plastic compounded with deca-BDE were soaked in several leaching solutions. Trace amounts were leached into distilled water, seawater, and acidic pepsin solution. In contrast, over 20 times as much material was leached into stomach oil, and over 50 times as much into fish oil (a major component of stomach oil). Analysis of abdominal adipose, liver tissue, and ingested plastics from 18 wild seabirds collected from the North Pacific Ocean showed the occurrence of deca-BDE or hexa-BDEs in both the tissues and the ingested plastics in three of the birds, suggesting transfer from the plastic to the tissues. In birds with BDE209 in their tissues, the dominance of BDE207 over other nona-BDE isomers suggested biological debromination at the meta position. Model calculation of PBDE exposure to birds based on the results of the leaching experiments combined with field observations suggested the dominance of plastic-mediated internal exposure to BDE209 over exposure via prey.

Feather corticosterone reveals developmental stress in seabirds.

In nest-bound avian offspring, food shortages typically trigger a release of the stress hormone corticosterone (CORT). Recent studies indicate that CORT is passively deposited in the tissue of growing feathers and thus may provide an integrated measure of stress incurred during development in the nest. The current hypothesis predicts that, assuming a constant rate of feather growth, elevated CORT circulating in the blood corresponds to higher levels of CORT in feather tissue, but experimental evidence for nutritionally stressed chicks is lacking. Here, we examined how food limitation affects feather CORT content in the rhinoceros auklet (Cerorhinca moncerata). We (i) used captive chicks reared on control versus restricted diets, and (ii) applied this technique to free-living chicks with unknown nutritional histories that fledged at three separate colonies. We found that (i) feather growth was not affected by experimentally induced nutritional stress; (ii) captive chicks raised on a restricted diet had higher levels of CORT in their primary feathers; (iii) feather CORT deposition is a sensitive method of detecting nutritional stress; and (iv) free-living fledglings from the colony with poor reproductive performance had higher CORT in their primary feathers. We conclude that feather CORT is a sensitive integrated measure revealing the temporal dynamics of food limitations experienced by rhinoceros auklet nestlings. The use of feather CORT may be a powerful endocrine tool in ecological and evolutionary studies of bird species with similar preferential allocation of limited resources to feather development.

Contamination status and accumulation characteristics of metals and a metalloid in birds on Teuri Island, Hokkaido, Japan.

Teuri Island, Hokkaido in Japan is an important place for seabirds breeding. We measured the concentrations of heavy metals (Hg, Cd, Cr, Co, Ni, Cu, Zn, and Pb) and a metalloid (As) in rhinoceros auklet (Cerorhinca monocerata) (n = 7), thick-billed murre (Uria lomvia) (n = 2), spectacled guillemot (Cepphus carbo) (n = 6), slaty-backed gull (Larus schistisagus) (n = 15), jungle crow (Corvus macrorhynchos) (n = 3), Japanese anchovy (Engraulis japonica) (n = 6) and Atka mackerel (Pleurogrammus azonus) (n = 2). Spectacled guillemot had high As concentrations, with its source being their feeding habitat. Concentration of Hg in kidney of jungle crow was higher than other seabird species at Teuri.

Contaminants in tracked seabirds showing regional patterns of marine pollution.

Ocean-scale monitoring of pollution is challenging. Seabirds are useful indicators because they travel over a broad foraging range. Nevertheless, this coarse spatial resolution is not fine enough to discriminate pollution in a finer scale. Previous studies have demonstrated that pollution levels are higher in the Sea of Japan and South and East China Seas than the Northen Pacific Ocean. To test these findings in a wide-ranging animal, we tracked streaked shearwaters (Calonectris leucomelas) from four islands in Japan using global positioning system (GPS) and measured persistent organic pollutants (POPs) in the oil of their preen glands. The POPs did not change during 6 to 21 days when birds from Awashima were foraging only in the Sea of Japan, while it increased when they crossed to the Pacific through the Tsugaru Strait and foraged along the eastern coast of Hokkaido where industrial cities occur. These results indicate that POPs in the oil reflect relatively short-term exposure. Concentrations of POPs displayed greater variation among regions. Total polychlorinated biphenyls were highest in birds foraging in a small area of the semiclosed Seto Inland Sea surrounded by urbanized coast, p,p'-dichlorodiphenyltrichloroethane (DDT) was highest in birds foraging in the East China Sea, and total hexachlorocyclohexanes were highest in birds foraging in the Sea of Japan. All were lowest in birds foraging in the Pacific. This distribution of POPs concentration partly agrees with previous findings based on mussels, fish, and seawater and possibly reflects the mobility and emission sources of each type of POP. These results highlight the importance of information on the foraging area of highly mobile top predators to make them more effective monitors of regional marine pollution.

Double congenital fistulae with aneurysm diagnosed by combining imaging modalities.

Congenital coronary pulmonary artery fistula (CAF) is rare, and systemic-to-pulmonary artery fistula (SPAF) is even more so. Furthermore, congenital coronary pulmonary fistula associated with congenital SPAF is extremely rare. As far as we know, CAF and SPAF connected with an aneurysm have not been described very often. We described an 83-year-old woman with an aneurysm originating from a CAF connected to an aortopulmonary artery fistula. Chest radiography revealed a shadow at the left edge of the heart line. Multi-detector-row computed tomography (MDCT) with contrast enhancement and coronary cine angiography revealed that the shadow was an aneurysm connected to a tortuous fistula at the left anterior descending coronary artery. The aneurysm was formed by congenital coronary pulmonary and aortopulmonary artery fistulae. Echocardiography revealed predominantly systolic blood flow in the fistula from the left anterior descending coronary artery (LAD). Although neither MDCT, echocardiography nor coronary angiography alone could provide a comprehensive image of the anomaly, including the hemodynamics in the fistulae and their relationship with surrounding organs and tissues, their combination could provided important facts the led to a deeper understanding of this very uncommon occurrence.

Heavy metal pollution in Japanese seabirds.

It is reported that seabirds accumulate high levels of metals, prompting concerns regarding poisoning. The present study investigated the accumulation patterns of metals in tissues among four species of seabirds (Fratercula corniculata, Uria lomvia, Puffinus tenuirostris, and Fulmarus glacialis). Furthermore, we focused on Slaty-backed Gulls, which accumulated high levels of cadmium and mercury, and compared the areal differences. Geographic variation of metal levels could also contribute to differences in metal accumulation levels in these bird species. Therefore, the concentrations of metals in seabirds are considered to reflect their habitat. There are differences in the accumulation pattern among the seabird species. The high accumulation of metals could affect seabirds even if they do not show any symptoms.

Growth differentiation factor-15 stimulates the synthesis of corticotropin-releasing factor in hypothalamic 4B cells.

Growth differentiation factor-15 (GDF15) is a stress-activated cytokine that regulates cell growth and inflammatory and stress responses. We previously reported the role and regulation of GDF15 in pituitary corticotrophs. Dexamethasone increases Gdf15 gene expression levels and production. GDF15 suppresses adrenocorticotropic hormone synthesis in pituitary corticotrophs and subsequently mediates the negative feedback effect of glucocorticoids. Here, we analyzed corticotropin-releasing factor (Crf) promoter activity in hypothalamic 4B cells transfected with promoter-driven luciferase reporter constructs. The effects of time and GDF15 concentration on Crf mRNA levels were analyzed using quantitative real-time polymerase chain reaction. Glial cell-derived neurotrophic factor family receptor α-like (GFRAL) protein is expressed in 4B cells. GDF15 increased Crf promoter activity and Crf mRNA levels in 4B cells. The protein kinase A and C pathways also contributed to the GDF15-induced increase in Crf gene expression. GDF15 stimulates GFRAL, subsequently increasing the phosphorylation of AKT, an extracellular signal-related kinase, and the cAMP response element-binding protein. Therefore, GDF15-dependent pathways may be involved in regulating Crf expression under stressful conditions in hypothalamic cells.

Biochemical Evaluation by Confirmatory Tests after Unilateral Adrenalectomy for Primary Aldosteronism.

Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Unilateral PA can be cured using unilateral adrenalectomy (Adx). PA surgery outcome (PASO) criteria, which include clinical and biochemical outcomes, have been proposed to evaluate PA cure after Adx. However, clinical outcomes are often inconsistent with biochemical outcomes. In addition, although confirmatory tests are included as endpoints of biochemical outcomes in the PASO criteria, their clinical usefulness has not yet been established. We evaluated clinical parameters and confirmatory test results before and after Adx in 16 patients with PA and assessed the usefulness of the confirmatory tests. The following were the clinical outcomes after Adx: 37.5% complete success, 62.5% partial success, and 0% absent success. The ratio of biochemical complete success was as follows: 69% aldosterone/renin ratio and basal plasma aldosterone concentration, 19% as assessed by the captopril challenge test, 47% as assessed by the saline infusion test, 30% as assessed by the furosemide upright test, and 100% urine aldosterone. Of these, biochemical complete success was judged in four cases by aldosterone/renin ratio and basal plasma aldosterone concentration, one case by captopril challenge test, five cases by saline infusion test, and one case by furosemide upright test. Although clinical outcomes and urine aldosterone levels improved after Adx, confirmatory tests failed to improve in some cases. The current criteria are not considered useful for biochemical evaluation after Adx. To determine whether additional treatment with mineralocorticoid receptor antagonists is required, more accurate biochemical criteria should be established after Adx.

Growth differentiation factor-15 modulates adrenocorticotropic hormone synthesis in murine AtT-20 corticotroph cells.

Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine that plays important roles in regulation of inflammatory responses, cell growth, and cell differentiation. However, the nature of these roles remains unclear. Here, we aimed to examine the regulatory effects of dexamethasone on Gdf15 expression in murine AtT-20 corticotroph cells. Human Gdf15 promoter-driven luciferase reporter constructs were transfected into corticotroph cells to analyze their promoter activity. The effects of time and concentration of dexamethasone on Gdf15 and proopiomelanocortin (Pomc) mRNA levels were assessed using quantitative real-time polymerase chain reaction. Dexamethasone induced Gdf15 transcription and mRNA levels as well as GDF15 production in transfected cells, whereas reduced the Pomc mRNA levels. GDF15 modulated adrenocorticotropic hormone (ACTH) synthesis, and the dexamethasone-mediated reduction in Pomc mRNA levels were partially relieved upon Gdf15 knockdown. We concluded that GDF15 modulated ACTH production in pituitary corticotrophs in an autocrine manner by suppressing Pomc expression and subsequently mediating the negative feedback effect of glucocorticoids, thereby contributing to pituitary stress response and homeostasis.