Search

The adrenal glands play a key role in maintaining the physiological balance of birds and helping them to survive environmental changes. The objective of the present work was to give a detailed investigation of the histological, ultrastructural, and immunohistochemical findings of the adrenal gland in Japanese quail during the prehatching phase. The current study was performed on 45 healthy Japanese quail embryos at different prehatching periods. Our results showed the primordium of the quail's adrenocortical tissue appeared at 3 days of incubation as a thickening of the splanchnic mesoderm. The prospective chromaffin cells appeared at 5 days as clusters of cells migrated from the neural crest cells along the dorsal aorta toward the interrenal tissue. TH immunoreactivity was observed in the neural crest cells during their migration toward the adrenal primordium. Furthermore, these TH immunopositive cells were intermingled with the developing interrenal cell cords that developed from the coelomic epithelium. NSE immunostaining was detected within the cytoplasm of interrenal cells, chromaffin cells, and ganglion cells. Sox10 is expressed in chromaffin and ganglion cells with different staining intensities. On the 13th day of prehatching, both interrenal and chromaffin cells were β-catenin immunonegative, but on the 17th day, both cells were immunopositively. Our findings show that during prenatal life, the adrenal gland undergoes significant morphological changes. Together, the present data suggest that studying the prenatal development of the adrenal gland in birds is important for advancing our understanding of this critical organ and its functions. RESEARCH HIGHLIGHTS: The present study aimed to give a detailed study of the histological, ultrastructural, and immunohistochemical investigations of the adrenal gland in Japanese quail during the prehatching period. The interrenal primordium was observed on the third embryonic day, on the fifth ED the primordium of the chromaffin tissue appeared as row of migrating neural crest cell. At the ultrastructural level, the interrenal cells take steroid-secreting cells characters, they have varying amounts of lipid droplets and abundant mitochondria at 15th ED contained moderate number of lysosomes and mitochondria., (© 2023 Wiley Periodicals LLC.)

The adrenal glands are paired abdominal endocrine organs vital to the bird's health. The present research aimed to provide a comprehensive examination of the histological, ultrastructural, and immunohistochemical investigations of the adrenal gland in Japanese quail during the post hatching period. The current study was performed on 21 healthy Japanese quail chicks at different post hatching periods. Our results showed the adrenal gland is surrounded by a connective tissue capsule, which consists of dense collagen fibers containing large blood vessels, chromaffin cells, autonomic ganglia, fibroblasts, and migrating Schwann cells. The zonation of the adrenal gland is composed of a subcapsular layer, a peripheral zone, and a central zone, which gets more pronounced with age. At the ultrastructural level, the interrenal cells take the steroid-secreting cells characters; they have varying amounts of lipid droplets and abundant mitochondria. Adrenal medullary chromaffin cells showed positive immunoreactivity to the NSE. With increasing age, the chromaffin tissue's Sox10 immunoreactivity increased. β-catenin is expressed within the plasmalemma and the cytoplasm of the interrenal and chromaffin cells and its reactivity increased with age, especially in the chromaffin cells. Our results indicate the adrenal gland undergoes significant morphological changes during the postnatal life. Overall, the postnatal period is an important time for the development and maturation of the adrenal glands., (© 2023 Wiley Periodicals LLC.)

Plasma membrane proteins are amenable to endocytosis assays since they are easily labeled by reagents applied in the extracellular medium. This has been widely exploited to study constitutive endocytosis or ligand-induced receptor endocytosis. Compensatory endocytosis is the mechanism by which components of secretory vesicles are retrieved after vesicle fusion with the plasma membrane in response to cell stimulation and a rise in intracellular calcium. Luminal membrane proteins from secretory vesicles are therefore transiently exposed at the plasma membrane. Here, we described an antibody-based method to monitor compensatory endocytosis in chromaffin cells and present an image-based analysis to quantify endocytic vesicles distribution.

The adrenal gland is an essential component of the body stress response; it is formed by two portions: a steroidogenic and a chromaffin tissue. Despite the anatomy of adrenal gland is different among classes of vertebrates, the hormones produced are almost the same. During stress, these hormones contribute to body homeostasis and maintenance of ion balance. The adrenal gland is very sensitive to toxic compounds, many of which behave like endocrine-disruptor chemicals (EDCs). They contribute to alter the endocrine system in wildlife and humans and are considered as possible responsible of the decline of several vertebrate ectotherms. Considering that EDCs regularly can be found in all environmental matrices, the aim of this review is to collect information about the impact of these chemical compounds on the adrenal gland of fishes, amphibians and reptiles. In particular, this review shows the different behavior of these "sentinel species" when they are exposed to stress condition. The data supplied in this review can help to further elucidate the role of EDCs and their harmful impact on the survival of these vertebrates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Despite being a highly conserved protein, the precise role of the mitochondrial translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), remains elusive. The void created by studies that overturned a presumptive model that described TSPO/PBR as a mitochondrial cholesterol transporter for steroidogenesis has been filled with evidence that it can affect mitochondrial metabolic functions across different model systems. We previously reported that TSPO/PBR deficient steroidogenic cells upregulate mitochondrial fatty acid oxidation and presented a strong positive correlation between TSPO/PBR expression and tissues active in triglyceride metabolism or lipid storage. Nevertheless, the highlighting of inconsistencies in prior work has provoked reprisals that threaten to stifle progress. One frequent factoid presented as being supportive of a cholesterol import function is that there are no steroid-synthesizing cell types without high TSPO/PBR expression. In this study, we examine the hamster adrenal gland that is devoid of lipid droplets in the cortex and largely relies on de novo cholesterol biosynthesis and uptake for steroidogenesis. We find that Tspo expression in the hamster adrenal is imperceptible compared to the mouse. This observation is consistent with a substantially low expression of Cpt1a in the hamster adrenal, indicating minimal mitochondrial fatty acid oxidation capacity compared to the mouse. These findings provide further reinforcement that the much sought-after mechanism of TSPO/PBR function remains correlated with the extent of cellular triglyceride metabolism. Thus, TSPO/PBR could have a homeostatic function relevant only to steroidogenic systems that manage triglycerides associated with lipid droplets.

Immunohistochemistry of human aldosterone synthase (CYP11B2) has revealed that most of aldosterone is autonomously produced in aldosterone-producing cell clusters (APCCs) beneath the capsule of adult adrenals rather than physiologically in the zona glomerulosa (ZG). APCCs have been occasionally found to harbor a somatic mutation of ion channel/pump genes, and number and size of APCCs increase with age until 50 years old. Herein, the objective of the study was to examine APCC development in 106 autopsied adrenals from 85 elderly individuals who died at ages from 50 to 103 years. We obtained the following results: (1) physiological CYP11B2 expression in ZG were attenuated in more elderly persons; (2) number and size of APCCs decreased with age; (3) detachment of APCC from the capsule appeared to occur occasionally over the wide range of the ages; and (4) incidental micro aldosterone-producing adenomas (APAs) and possible APCC-to-APA transitional lesions (pAATLs) were found primarily in samples from persons aged 50-60 years but not in samples from more elderly persons; pAATL was a putative designation based on our previous results indicating that it consisted of subcapsular APCC-like portion and inner APA-like portions. Thus, the formation of the CYP11B2-expressing lesions as well as thickening of the ZG in the adrenals were inversely correlated with age of death in the individuals aged over 50 years. Considering that autopsy samples were used in this study, inactive production of aldosterone regardless of autonomous or physiological manners may have survival advantages in individuals aged over 50 years., (Copyright © 2019. Published by Elsevier Ltd.)

Autophagy plays a vital role in embryonic development and cell differentiation. Our previous study demonstrated that prenatal ethanol exposure (PEE) resulted in intrauterine growth retardation (IUGR) and adrenal developmental toxicities in rat offspring. The present study focused on PEE-induced autophagy as an underlying mechanism and its biological significance in female fetal rats. Female fetuses in the PEE group exhibited lower body weights and suffered adrenal structural abnormalities compared to the controls. Cell proliferation was inhibited, the insulin-like growth factor 1 (IGF1) pathway was reduced, and autophagy was activated in the glands of female fetal rats. Ethanol increased the ratio of microtubule-associated protein light chain 3 beta-II (LC3β-II) to LC3β-I in vitro, and it reduced cortisol levels in time- and concentration-dependent manners in human adrenocortical carcinoma cells (NCI-H295A). Bafilomycin A1 inhibited autophagy, steroidogenic factor 1 (SF1) protein and steroidogenesis in the present study. Rapamycin with ethanol up-regulated autophagy and SF1 expression and activated steroidogenesis when compared with ethanol alone. In addition, ethanol inhibited IGF1 receptor (IGF1R) and phospho-mTOR (Ser2448) expression in a concentration-dependent manner. These results demonstrate that PEE activated autophagy in fetal adrenal glands, and the underlying mechanism may be associated with inhibition of the IGF1R/phospho-mTOR (Ser2448) pathway. Autophagy may be a compensatory mechanism for the PEE-induced inhibition of fetal adrenal steroidogenesis to maintain fetal adrenal development., (Copyright © 2018. Published by Elsevier Inc.)

Crotamine is a cationic, non-enzymatic, protein integrating a minor family of myotoxins, composed of 42 amino acid residues, described in Viperidae and Crotalidae snake's families that has been used in neuroscience research, drug progressing and molecular diversity reports. Crotamine-like protein (CLP) from C.o.helleri venom was isolated in fraction 5 from 7 peaks obtained by sulfopropyl waters protein pak cationic exchange column. In tricine-SDS-PAGE under non-reduced conditions this CLP showed a single band of ~8 kDa molecular weight. CLP induced toxicity of K-562 cells with a CC 50 of 11.09 µM. In mice adrenal gland after 24 h of CLP injection, cortical cells exhibited swollen mitochondria with scarce tubular cristae, some elements of smooth and rough endoplasmic reticula, widened nuclear envelope, slightly osmiophilic lipid droplets, and autophagic vacuoles. In some areas cortical cells plasma membrane and endothelial walls disappeared, which indicated a necrosis process. In other areas, endothelial cell cytoplasm did not present the normal caveolae and pinocytotic vesicles. To our knowledge, this is the first report on mice adrenal gland damages, caused by the injection of CLP from rattlesnakes. Our results propose that adrenal cortex lesions may be significant in the envenoming etiopathogenesis by CLP.

In the present study, we examined the morphological features of the adrenal gland in Bactrian camel by means of digital anatomy, light and electron microscopy. Our findings testified that the gland was divided into three parts, capsule, cortex and medulla from outside to inside as other mammals, and the cortex itself was further distinguished into four zones: zona glomerulosa, zona intermedia, zona fasciculate and zona reticularis. Notably, the zona intermedia could be seen clearly in the glands from females and castrated males, whereas it was not morphologically clear in male. There was a great deal of lipid droplets in the zona fasciculate, while it was fewer in the zona glomerulosa and zona reticularis. The cytoplasm of adrenocortical cell contained rich mitochondria and endoplasmic reticulum. The adrenal medulla was well-developed with two separations of external and internal zones. The most obvious histological property of adrenal medulla cells were that they contained a huge number of electron-dense granules enveloped by the membrane, and so medulla cells could be divided into norepinephrine cells and epinephrine cells. Moreover, the cortical cuffs were frequently present in adrenal gland. Results of this study provides a theoretical basis necessary for ongoing investigations on Bactrian camels and their good adaptability in arid and semi-arid circumstances., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Aging is a multifactorial process characterized by organ loss of function and degeneration, but the mechanisms involved remain elusive. We have shown recently that catecholamine metabolism drives the accumulation of mitochondrial DNA (mtDNA) deletions in dopaminergic cells, which likely contribute to their degeneration during aging. Here we investigated whether the well-documented degeneration and altered function of adrenals during aging is linked to catecholamine production in the medulla followed by accumulation of mtDNA deletions., Material and Methods: We analyzed adrenal medullary and cortical samples of both murine and human origin covering a wide range of ages for mtDNA deletion content, mtDNA copy number, mitochondrial and cellular integrity as well as aging-related tissue changes such as fibrosis., Results: Indeed, we demonstrate in mice and humans that the adrenal medulla accumulates a strikingly high amount of mtDNA deletions with age, causing mitochondrial dysfunction in the adrenal medulla, but also in the cortex, accompanied by apoptosis and, more importantly, by severe inflammation and remarkable fibrosis. Additionally, a concomitant and dramatic loss of medullary and cortical cells is observed in old animals., Conclusion: Our results show that accumulation of mtDNA deletions, and the ensuing mitochondrial dysfunction, is a hallmark of adrenal aging, further strengthening the hypothesis that catecholamine metabolism is detrimental to mtDNA integrity, mitochondrial function and cell survival. Moreover, the cell loss potentially induced by mitochondrial dysfunction could explain the decline in adrenal hormonal and steroidal secretion during aging., (© 2016 S. Karger AG, Basel.)

Background: Poly(ADP-ribose) polymerase (PARP) participates in multi-organ failure in various inflammatory diseases including acute necrotizing pancreatitis (ANP). Since pancreatitis-associated adrenal insufficiency is partly caused by inflammatory damage to the adrenal cortex, we examined whether PARP antagonism could alleviate adrenal insufficiency in a rat model of ANP., Methods: ANP was induced by retrograde infusion of sodium taurocholate into the bile-pancreatic duct. At 30 min prior to taurocholate infusion, rats were pretreated with the PARP inhibitor 3-Aminobenzamide (3-AB, 20 mg/kg) or vehicle. Pancreatic pathological injury, adrenal histology, neutrophil infiltration, cell apoptosis, and serum corticosterone level were assessed at various times points. Activities of poly(ADP-ribosyl)ated protein (PAR), nuclear factor-kappaB (NF-kB), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS) in the adrenal were also examined., Results: PARP overactivation in ANP rats is associated with reduced serum corticosterone level and marked cellular alterations in adrenocortical tissue. Inflammatory stress caused by ANP reduced adrenal corticosterone release. 3-AB reduced the activation of PARP and inflammatory markers, decreased myeloperoxidase activity, attenuated adrenal morphologic lesions and cells apoptosis, simultaneously improved the impaired adrenal function., Conclusions: Our data demonstrate the involvement of PARP overactivation in the pathogenesis of adrenal dysfunction after ANP. PARP inhibition may suppress inflammation and promote functional recovery from adrenal injury.

Silent subtype III pituitary adenomas (SS-3) are nonfunctioning radiosensitive adenomas that may be associated with an increased risk of recurrence and invasion. The features that have been proposed to be diagnostically important are identifiable by electron microscopy (EM) and include an enlarged Golgi apparatus, along with several other ultrastructural features. The often limited availability of EM and the uncertainty about the relative importance of individual features pose practical challenges to the diagnosis. We hypothesized that it may be possible to diagnose SS-3 based solely on a markedly enlarged Golgi apparatus identified at the light microscopic level. In this prospective study, we used immunohistochemistry (IHC) for the Golgi apparatus with the MG-160/GLG-1 antibody to identify 10 cases with features suggestive of SS-3. Electron microscopy was performed for confirmation on 1 case. Compared with a control group of 20 conventional null cell adenomas, the SS-3 adenomas showed an increased MIB-1 proliferation index (p < 0.01), a higher risk of invasion (p < 0.01), and a higher incidence of recurrence (p < 0.01). Thus, in this first controlled study, we demonstrate that SS-3 is clinically aggressive and identifiable by IHC, without the need for EM. The routine diagnostic workup of nonsecreting adenomas should rule out SS-3, which can be done quickly and efficiently by IHC.

Background: Spironolactone is often used to treat hypertension caused by hyperaldosteronism, and as a result, can form concentrically laminated electron dense spironolactone body inclusions within the adrenal gland. Spironolactone bodies have not been investigated in a contemporary cohort or in patients treated with the more recently approved aldosterone antagonist, eplerenone., Methods: Spironolactone bodies were retrospectively investigated in patients treated for hyperaldosteronism (n=15) from 2012-2013 that underwent a subsequent adrenalectomy., Results: Inclusions were identified in 33% of patients treated with aldosterone antagonists, far less than previously reported. Remarkably, 50% of patients treated with spironolactone had inclusions while no patients using eplerenone alone had inclusions. Two patients treated with spironolactone had bodies present longer than the duration described in prior studies. Inclusions unexpectedly persisted in 1 patient despite increased duration of discontinued pharmacological treatment. A spectrum of histologic and ultrastructural findings were encountered within an adrenal cortical adenoma from a patient treated with both spironolactone and eplerenone. Ultrastructural examination revealed laminated electron dense bodies with the appearance of classic spironolactone inclusions as well as electron dense bodies without laminations and laminated bodies without electron dense cores., Conclusions: Our incidence rate of spironolactone bodies was much lower than previously reported, with no inclusions seen in patients treated solely with the newer aldosterone antagonist, eplerenone. Pathologists should be aware of these infrequently encountered inclusions, particularly as the clinical history of hyperaldosteronism and pharmacologic treatment may not be provided., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4597918761268031.

Nonylphenol (NP) is an endocrine disruptor widely distributed in the environment. It accumulates in the lipids of living organisms and enters the human food chain. The main source of human exposure is expected to be food, drinking water and foodstuff contaminated through leaching from packaging or pesticide formulation applications. NP acts as an estrogenic compound and it is able to mimic the action of estradiol 17β (E2) by binding to the estrogen receptor (ER). The aim of the present study was to investigate the NP effects on the hypothalamic-pituitary-adrenal gland (HPA) axis of the bioindicator Podarcis sicula lizard. A time-dependent stimulation of the HPA axis and variations of both catecholamine plasma levels were showed. Moreover, NP effects on adrenal gland morphology were evaluated by light and transmission electron microscopy. Clear morphological signs of adrenal gland stimulation such as an increase of steroidogenic cord diameter and vascularization, a strong escalation of adrenaline cell number and a decrease of noradrenaline cells were observed. The notably elevated levels of adrenal hormones suggested a permanent turning on of hypothalamic corticotropin releasing factor (CRF) secretion together with a lack of the negative feedback of HPA axis, perturbing systemic responses of the organism. Our data may help to predict the biological alterations induced by NP and to extend its impact upon adrenal function., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In this work we have compared the ultrastructural characteristics of major pancreatic endocrine cells, pituitary melanotrophs and adrenal chromaffin cells in the normal mouse strain (wild type, WT) and mice with a known secretory deficit, the Rab3a knockout strain (Rab3a KO). For this purpose, pancreata, pituitary glands and adrenal glands from the Rab3a KO and from the WT mice were analysed, using conventional transmission electron microscopy (TEM). In order to assess the significance of the presence of Rab3a proteins in the relevant cells, we focused primarily on their secretory vesicle morphology and distribution. Our results showed a comparable general morphology in Rab3a KO and WT in all assessed endocrine cell types. In all studied cell types, the distribution of secretory granules along the plasma membrane (number of docked and almost-docked vesicles) was comparable between Rab3a KO and WT mice. Specific differences were found in the diameters of their secretory vesicles, diameters of their electron-dense cores and the presence of autophagic structures in the cells of Rab3A KO mice only. Occasionally, individual electron-dense round vesicles were present inside autophagosome-like structures; these were possibly secretory vesicles or their remnants. The differences found in the diameters of the secretory vesicles confirm the key role of Rab3a proteins in controlling the balance between secretory vesicle biogenesis and degradation, and suggest that the ablation of this protein probably changes the nature of the reservoir of secretory vesicles available for regulated exocytosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Tumors of the adrenal glands are among the most frequent tumors in cattle; however, few studies have been conducted to describe their characteristics. The aim of this study was to classify 41 bovine adrenal neoplasms from 40 animals based on macroscopic and histologic examination, including electron microscopy and immunohistochemistry for melan A, synaptophysin, chromogranin A, vimentin, pan-cytokeratin, 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase), and Ki-67. The tumors were classified as 23 adrenocortical adenomas, 12 adrenocortical carcinomas, 2 schwannomas, 2 pheochromocytomas (1 malignant), and 1 ganglioneuroma. Five histologic features were characteristic of metastasizing adrenocortical tumors: invasion of the capsule, vascular invasion, diffuse growth pattern, spindle-cell morphology, and nuclear pleomorphism. Adrenocortical tumors with at least 3 of these features were classified as malignant. Immunohistochemically, adrenocortical tumors expressed melan A (16/19), vimentin (14/26), cytokeratin (11/26), and chromogranin A (9/27), whereas pheochromocytomas expressed chromogranin A (2/2), synaptophysin (2/2), and vimentin (1/2). Both schwannomas expressed CNPase. An immunohistochemistry panel consisting of antibodies against melan A, synaptophysin, and CNPase was considered most useful to classify bovine adrenal tumors. However, the distinction between benign and malignant adrenocortical tumors was based on histologic features as in human medicine.

MicroRNAs (miRNAs) are small non-coding RNAs that participate in a large variety of biological processes. In this paper, the spatiotemporal expression pattern of miR-370 was characterized during mouse embryonic development, and was found to be stage- and tissue-specifically expressed. In addition, through luciferase reporter assays and western blot analyses, DNA methyltransferase 3A (Dnmt3a) was identified as a directly regulated target of miR-370. Altogether, our results indicate that miR-370 may play important roles in the morphogenesis of diverse organs, especially brain and adrenal glands, by mediating Dnmt3a expression during mouse development., (Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Transmissible spongiform encephalopathies (TSEs) or prion diseases are associated with accumulations of disease specific PrP (PrP(d)) in the central nervous system (CNS) and often the lymphoreticular system (LRS). Accumulations have additionally been recorded in other tissues including the peripheral nervous system and adrenal gland. Here we investigate the effect of sheep scrapie on the morphology and the accumulation of PrP(d) in the adrenal medulla of scrapie affected sheep using light and electron microscopy. Using immunogold electron microscopy, non-fibrillar forms of PrP(d) were shown to accumulate mainly in association with chromaffin cells, occasional nerve endings and macrophages. PrP(d) accumulation was associated with distinctive membrane changes of chromaffin cells including increased electron density, abnormal linearity and invaginations. Internalisation of PrP(d) from the chromaffin cell plasma membrane occurred in association with granule recycling following hormone exocytosis. PrP(d) accumulation and internalisation from membranes is similarly associated with perturbations of membrane structure and trafficking in CNS neurons and tingible body macrophages of the LRS. These data suggest that a major toxic effect of PrP(d) is at the level of plasma membranes. However, the precise nature of PrP(d)-membrane toxicity is tissue and cell specific suggesting that the normal protein may act as a multi-functional scaffolding molecule. We further suggest that the co-localisation of PrP(d) with exocytic granules of the hormone trafficking system may provide an additional source of infectivity in blood.

Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disorder caused by a deficiency in the activity of the lysosomal hydrolase, sulphamidase, an enzyme involved in the degradation of heparan sulphate. MPS IIIA patients exhibit progressive mental retardation and behavioural disturbance. While neuropathology is the major clinical problem in MPS IIIA patients, there is little understanding of how lysosomal storage generates this phenotype. As reduced neuronal communication can underlie cognitive deficiencies, we investigated whether the secretion of neurotransmitters is altered in MPS IIIA mice; utilising adrenal chromaffin cells, a classical model for studying secretion via exocytosis. MPS IIIA chromaffin cells displayed heparan sulphate storage and electron microscopy revealed large electron-lucent storage compartments. There were also increased numbers of large/elongated chromaffin granules, with a morphology that was similar to immature secretory granules. Carbon fibre amperometry illustrated a significant decrease in the number of exocytotic events for MPS IIIA, when compared to control chromaffin cells. However, there were no changes in the kinetics of release, the amount of catecholamine released per exocytotic event, or the amount of Ca(2+) entry upon stimulation. The increased number of large/elongated granules and reduced number of exocytotic events suggests that either the biogenesis and/or the cell surface docking and fusion potential of these vesicles is impaired in MPS IIIA. If this also occurs in central nervous system neurons, the reduction in neurotransmitter release could help to explain the development of neuropathology in MPS IIIA., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objective: The effects of drinking boron exposure on the mass, organ indexes and structure of adrenal gland were studied in the paper. Methods 192 Sprague-Dawley rats (28 +/- 2 days) with no bacteria infecting were divided into six groups (n = 32, male = female) randomly. Treated rats drunk the distilled water which supplemented with boron of 0, 40, 80, 160, 320 and 640 mg/L, respectively, for 60 days. At the 30th and the 60th day of experiment, 16 rats (n = 8, male = female) of each group were selected and made into narcosis with 10% Chloral Hydrate. The adrenal glands were obtained, weighted and fixed after dissection, then the samples were made into paraffin sections, stained with HE stain and chromaffin, observed and photographed by Olympus CH-30 microphotograph system., Results: Compared with control group, the average mass of adrenal gland of male rats in each experiment group decreased significantly or most significantly at the 30th day of experiment (P < 0.05 or P < 0.01), but the index of adrenal gland of male rats in the group of 640 mg/L boron at 60th day of experiment increased significantly (P < 0.05). Under the microscope, the microstructure of adrenal gland of rats in the group of 40 mg/L boron were better obviously than control group, and the numbers of chromaffin granules in chromaffin cell increased obviously. The histopathological changes of different degree could be observed in the group of 80 to 640 mg/L boron, and they became remarkable with the boron supplementation. By comparative observation, the damage of cells in adrenal medulla appeared ahead of them in adrenal cortex, and the pathological change of adrenal gland in male rats were obvious than female rats., Conclusion: Drinking supplemented with 40 mg/L boron could prompt the structure of adrenal gland in rats, but could cause different degree damage, or even obvious toxic effect when the concentration of boron supplementation in drinking from 80 to 640 mg/L.

The effects of training are dependent on complex, adaptive changes which are induced by acute physical exercise at different levels. In particular, evidence shows that the hypothalamus-pituitary-adrenocortical axis, as well as the sympatho-adrenomedullary system, is mainly involved in mediating the physiological effects of physical exercise. The aim of the present study was to investigate, through a morphological and biochemical approach, the effects of training on the adrenal gland of mice, following two different protocols consisting of either low- or high-intensity training. Mice were run daily on a motorised treadmill for 8 weeks, at a velocity corresponding to 60% (low-intensity exercise) or 90% (high-intensity exercise) of the maximal running velocity previously determined by an incremental exercise test. We found that physical exercise produced an increase in the adrenal gland size compared with the control (sedentary) mice. The increase was 31.04% for mice that underwent high-intensity exercise and 10.08% for mice that underwent low intensity exercise, and this appeared to be the result of an increase in the area of both the adrenal cortex and adrenal medulla. Morphological analysis of the adrenal cortex showed that both types of exercise produced an increase in cytoplasmic vacuoles in steroidogenic cells, appearing more abundant after high-intensity exercise. No change was found in the reticulate zone. In the adrenal medulla, despite the absence of morphological changes, immunohistochemistry for tyrosine hydroxylase, dopamine β-hydroxylase and phenyl-ethanolamine-N-methyltransferase demonstrated an increased immunopositivity for these cathecolamine-synthesizing enzymes after intense exercise. These results were confirmed by immunoblot accompanied by densitometric analysis.

The aim of our study was to verify whether environmental concentrations of nonylphenol influenced the adrenal gland of Triturus carnifex. Newts were exposed to 19 μg/L nominal concentration of nonylphenol throughout the periods of December-January and March-April, corresponding to different stages of the chromaffin cell functional cycle. The morphological features of the steroidogenic and chromaffin tissues, and the serum levels of ACTH, aldosterone, corticosterone, norepinephrine and epinephrine were evaluated. Nonylphenol did not influence ACTH serum levels. During the two periods examined, the steroidogenic tissue had the same reaction: the quantity of cytoplasmic lipids, and the corticosteroid serum levels, decreased, suggesting the inhibition of synthesis and release of corticosteroids. During the two periods examined, the chromaffin tissue reacted differently to nonylphenol. During December-January, the numeric ratio of norepinephrine granules to epinephrine granules, and the epinephrine serum levels, increased, suggesting the stimulation of epinephrine release. During March-April, the numeric ratio of norepinephrine granules to epinephrine granules did not change, and the norepinephrine serum levels decreased, suggesting the inhibition of norepinephrine release. Our results show that nonylphenol influences the activity of the newt adrenal gland; considering the physiological role of this gland, our results suggest that nonylphenol may contribute to amphibian decline., (Copyright © 2011. Published by Elsevier Inc.)

Objective: To explore the values of adrenocorticotropic hormone receptor (ACTH-R) determination and ultrastructural observation of tumor cells in the subtyping of adrenocortical neoplasms (ANs)., Methods: The expression of ACTH-R in 87 AN tissues were determined with Polymer immunohistochemical staining, with 10 normal adrenal tissues as the controls. The ultrastructure of the tumor cells was observed using electron microscopy., Results: The positive expression rate of ACTH-R was (80.1 +/- 8.2)%, (53.2 +/- 10.3)%, (63.2 +/- 10.1)%, (83.3 +/- 6.5)%, and (70.1 +/- 7.3)% in the sub-CPA group, CPA group, APA group, NFA group, and NC group, respectively. ACTH-R expression was significantly higher in NFA and sub-CPA groups than in NC group (P = 0.001, P = 0.000), APA group (P = 0.000, P = 0.000), and CPA group (P = 0.000, P = 0.000), and was also significantly different between NC group and APA group (P = 0.039) and between APA group and CPA group (P = 0.037). However, no significant difference was found between NFA group and sub-CPA group (P = 0.325). As shown by the electron microscopy, ANs had some partially similar microscopic features, while different AN subtypes showed differences in the type and amount of secretory granules., Conclusion: ACTH-R determination and ultrastructural observation of tumor cells may be helpful for subtyping ANs.

Hypoplasia adrenal congenita is an extremely uncommon disease of early onset. This condition can be lethal in the absence of treatment. Some forms are due to the congenital adrenal hypoplasia of anencephalic type whose origin is even unknown. Here, we present two cases of congenital adrenal hypoplasia of anencephalic type with pituitary abnormalities. The two male newborns died because adrenal insufficiency in the neonatal period. The adrenal glands were hypoplastic with a histological structure of anencephalic type Immunocytochemical study of the pituitary revealed an absence of the gonadotrophs. No mutation of DAX 1 and SF-1 was found., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Objective: This study was aimed to see the histophysiological changes of the pineal and adrenal glands under altered photoperiodic conditions due to the administration of melatonin in the male domestic pigeon, Columba livia Gmelin., Methods: Young adult male domestic pigeons were exposed to long photoperiod (LP; 20 hr light: 4 hr dark), short photoperiod (SP; 4 hr light: 20 hr dark) exogenous melatonin (MEL; 20 microg/100 g body weight/day) was administered for 60 days in the primary breeding and regressive phase. At the end of experiment, adrenal and pineal glands were quickly dissected and processed for histology, ultrastructure study, biochemical, histochemical and immunohistochemical analysis., Results: In the primary breeding phase, the number of mitochondria and rough endoplasmic reticulum were increased in the adrenal gland in MEL-LP group, while lipid granules were also increased in the subcapsular zone. In MEL-SP treated group, however, the number of mitochondria decreased. Pinealocytes were increased in size and well-developed Golgi complexes were present near the cell nucleus after induction with MEL-LP treatment during the primary breeding phase. No remarkable changes were noticed in the number of mitochondria. In the regressive phase-I, the adrenocortical cytoplasm showed similar morphological features both in MEL-LP treatment and control groups. In pinealocytes, few rough endoplasmic reticulum and lipid droplets and moderate number of mitochondria were present. In MEL-SP treatment, increased number of mitochondria in the adrenocortical cells and decreased nuclear diameter of the pinealocytes were noticed. Few mitochondria were observed within the pinealocyte cytoplasm. Side chain cleavage enzyme (immunocytochemical) activity was increased in the subcapsular zone in MEL-LP treated group., Conclusions: The present data indicates that the changes in pineal and adrenocortical tissue histophysiology might be due to melatonin rhythm and light/dark regime which act as a modulator in the male domestic pigeon.

A fusion pore composed of lipid is an obligatory kinetic intermediate of membrane fusion, and its formation requires energy to bend membranes into highly curved shapes. The energetics of such deformations in viral fusion is well established, but the role of membrane bending in Ca(2+)-triggered exocytosis remains largely untested. Amperometry recording showed that during exocytosis in chromaffin and PC12 cells, fusion pores formed by smaller vesicles dilated more rapidly than fusion pores formed by larger vesicles. The logarithm of 1/(fusion pore lifetime) varied linearly with vesicle curvature. The vesicle size dependence of fusion pore lifetime quantitatively accounted for the nonexponential fusion pore lifetime distribution. Experimentally manipulating vesicle size failed to alter the size dependence of fusion pore lifetime. Manipulations of membrane spontaneous curvature altered this dependence, and applying the curvature perturbants to the opposite side of the membrane reversed their effects. These effects of curvature perturbants were opposite to those seen in viral fusion. These results indicate that during Ca(2+)-triggered exocytosis membrane bending opposes fusion pore dilation rather than fusion pore formation. Ca(2+)-triggered exocytosis begins with a proteinaceous fusion pore with less stressed membrane, and becomes lipidic as it dilates, bending membrane into a highly curved shape., (Copyright (c) 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Adenomatoid tumors (AT) are usually found in the genital tract of both sexes. They are very rarely located in extragenital sites, and are exceedingly rare in the adrenal. AT of the adrenal gland (AT-AG) are nonfunctioning, usually discovered incidentally and confused on imaging with other more common adrenal neoplasms. The overwhelming majority occur in males. Thirty-four cases have been reported so far, more often presenting grossly as solid tumors, rarely as solid with cystic areas, and 5 cases were almost entirely cystic. At histology they can be either circumscribed or locally infiltrative, and may pose diagnostic difficulties when the pathologist relies on morphology alone or is challenged on frozen section. On light microscopy the diagnosis may be very difficult if the tumor is rich in vacuolated cells, mimicking metastatic signet ring-cell adenocarcinoma. Immunophenotyping and/or electron microscopy are paramount in helping to ascertain their mesothelial lineage. Lymphangioma is the main histologic mimic of solid-cystic and cystic AT-AG, but lymphangioma is immunopositive for endothelial markers and negative for cytokeratins and mesothelial markers. Ultrastructural analysis has been performed in 10 published cases of AT-AG, in all of which the classical microvilli of coelomic type were always observed. In brief we report herein the sixth case of cystic lymphangioma-like AT, which was incidentally discovered during clinical follow-up in a 39-year-old man undergoing cancer staging and surveillance after surgery. The adrenal tumor was 5.5 cm in size and was fully investigated immunohistochemically and ultrastructurally. A complete review of the literature is also presented.

The morphology of the adrenal gland has been studied for a number of animal species all over the world, yet the detailed data about ostrich chick has not been reported. In the present study, the morphological features of the adrenal gland in African ostrich chicks were investigated by means of gross anatomy, light and electron microscope. Differences between the left and right adrenal glands were found in shape, size and location. The interrenal tissue and chromaffin cell interdigitated irregularly. The interrenal tissue was divided into a peripheral zone (PZ) and a central inner zone (CZ), and the PZ was further distinguished into an outer area (subcapsular zone, SCZ) and an inner area (IZ). The cellular arrangement in these zones showed evident zonation that resembled the mammalian. This phenomenon had been previously described only for the pelicanus. The cytoplasm of interrenal cells in SCZ was stained lightly than in IZ and CZ, and contained several vacuoles. Additionally, unlike CZ cells, SCZ cells appeared to contain more mitochondria and less lipid droplets. Two types of chromaffin cells: epinephrine cells and norepinephrine cells could be detected. The type 1 granules possessed a central core and a variable distance between membrane and core; the type 2 granules had an eccentric core, which leant to one side of granule and sticked to the membrane, giving a lager lacouna appearance in another side of the granule.

Exposure to antiandrogens during the critical developmental window (i.e. sexual differentiation) can permanently demasculinize the male phenotype. Here we have investigated the effects of developmental exposure to di-isononylphthalate (DINP) (250 and 750 mg/kg) and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE) (50 and 100mg/kg) on 19.5-day-old fetal Sprague-Dawley rat testicular and adrenal steroidogenesis. Maternal exposure to DINP or p,p'-DDE on embryonic days (EDs) 13.5-17.5 did not down-regulate the activity of steroidogenesis in ED 19.5 male rat fetus. Protein expression levels of testicular and adrenal StAR, P450scc, 3beta-HSD and androgen receptor (AR) did not show any changes. However, p,p'-DDE caused clear abnormalities in the ultrastructure of steroidogenic cells in ED 19.5 rat testis and adrenal. These structural alterations can disturb the development and function of fetal testis and adrenal that may become evident later in life.

Background: Adrenal chromaffin cells and sympathetic neurons both originate from the neural crest, yet signals that trigger chromaffin development remain elusive. Bone morphogenetic proteins (BMPs) emanating from the dorsal aorta are important signals for the induction of a sympathoadrenal catecholaminergic cell fate., Results: We report here that BMP-4 is also expressed by adrenal cortical cells throughout chick embryonic development, suggesting a putative role in chromaffin cell development. Moreover, bone morphogenetic protein receptor IA is expressed by both cortical and chromaffin cells. Inhibiting BMP-4 with noggin prevents the increase in the number of tyrosine hydroxylase positive cells in adrenal explants without affecting cell proliferation. Hence, adrenal BMP-4 is likely to induce tyrosine hydroxylase in sympathoadrenal progenitors. To investigate whether persistent BMP-4 exposure is able to induce chromaffin traits in sympathetic ganglia, we locally grafted BMP-4 overexpressing cells next to sympathetic ganglia. Embryonic day 8 chick sympathetic ganglia, in addition to principal neurons, contain about 25% chromaffin-like cells. Ectopic BMP-4 did not increase this proportion, yet numbers and sizes of 'chromaffin' granules were significantly increased., Conclusion: BMP-4 may serve to promote specific chromaffin traits, but is not sufficient to convert sympathetic neurons into a chromaffin phenotype.

The aim of the present study was to verify if human FSH influences the adrenal gland of the newt, Triturus carnifex. Newts were given intraperitoneal injections of human FSH throughout the periods of February-March, and December-January; periods in which newt FSH levels are normally very low. The effects of human FSH on adrenal gland activity were observed in the morphological features of the steroidogenic and chromaffin adrenal cells, and in the serum levels of aldosterone, corticosterone, norepinephrine and epinephrine. The effect of human FSH on the steroidogenic cells was significant during the February-March period; the quantity of cytoplasmic lipids decreased, and the corticosteroid serum levels increased. During the December-January period, the human FSH effects were negligible. The effect of human FSH on the chromaffin cells was significant during both the February-March, and the December-January periods. During February-March, the human FSH increased the numeric ratio of norepinephrine granules to epinephrine granules, and increased the epinephrine serum levels. During December-January, the human FSH decreased the numeric ratio of norepinephrine granules to epinephrine granules, and increased the norepinephrine serum levels. The results of the present study show that human follicle-stimulating hormone influences the activity of the newt adrenal gland, thus indicating a relationship between the annual sexual cycle and the annual adrenal cycle of the newt.

Steroids are synthesized mainly from the adrenal glands catalyzed by steroidogenic enzymes; the expression of these enzymes is controlled by transcription factor steroidogenic factor-1 (SF-1; NR5A1). To understand the physiological effect of genetic changes on steroid secretion, we used Cre-LoxP and gene targeting technology to mutate the binding sequence for SF-1 (SF-1 response element) on the promoter of the mouse Cyp11a1 gene, which encodes a critical enzyme for steroid biosynthesis. The resulting Cyp11a1 L/L mice expressed about 7-fold less cytochrome P450 side-chain cleavage enzyme (CYP11A1) in the adrenal and testis but expressed normal amounts of CYP11A1 in the placenta and ovary. This tissue-specific reduction of gene expression did not affect basal steroid secretion but attenuated the circadian rhythm of glucocorticoid secretion. These mice also failed to induce glucocorticoid secretion in response to stress, leading to retention of CD4+CD8+ double-positive thymocytes. Unlike complete Cyp11a1 disruption, which causes neonatal death, promoter mutation did not decrease life span and caused no defect in reproduction. Thus, CYP11A1 appears in normal mice to be expressed above the minimal required level, providing a large capacity for use in response to stress. Mutation of the SF-1 response element of Cyp11a1 results in reduced stress response due to decreased adrenal CYP11A1 expression and insufficient stress-induced glucocorticoids secretion.

The sole structural determinant for the differential ability of the insulin-like growth factors (IGF-I and IGF-II) to induce autophosphorylation of specific insulin receptor (IR) tyrosine residues and activate downstream signaling molecules is the C domain. The IR is structurally related to the type I insulin-like growth factor receptor (IGF-IR). This study aimed to identify the presence of IGF receptors by which the IGF-II C-peptide could mediate its effects in the frog (Rana ridibunda) adrenal glands and to observe whether injection of IGF-II C-peptide affects the function of adrenal steroidogenic cells using light and transmission electron microscopy and by the evaluation of the immunoreactivity of steroidogenic acute regulatory protein (StAR). After IGF-II C-peptide injection, there was a reduction of StAR protein immunoreactivity levels, an accumulation of large lipid droplets in close contact with each other, and an induction of proliferation of the steroidogenic cells. These results indicate a possible role of IGF-II C-peptide in steroidogenic cell function and in induction of steroidogenesis. The detection in this study of IGF-I receptor (IGF-IR) immunoreactivity in frog adrenal glands also indicates that the metabolic and mitogenic effects of IGF-II C-peptide in these glands may occur via the IGF-IR.

Adrenal glands are common sites of diseases. With dramatically increased use of computed tomography (CT) and magnetic resonance (MR) imaging, more and more uncommon adrenal masses have been detected incidentally at abdominal examinations performed for other purposes. In this article, uncommon adrenal masses are classified as cystic masses (endothelial cysts, epithelial cysts, parasitic cysts, and pseudocysts), solid masses (ganglioneuroma, ganglioneuroblastoma, extramedullary plasmacytoma (EMP), neurilemmoma, and lymphoma), fat-containing masses (myelolipoma, teratoma), and infectious masses (tuberculoma), and the imaging features of these uncommon masses are demonstrated. Although most of these lesions do not have specific imaging features, some fat-containing masses and cystic lesions present with characteristic appearances, such as myelolipoma, teratoma, and hydatid. Combination with histopathologic characteristic of these uncommon masses of adrenal gland, radiological features of these lesions on CT and MR imaging can be accurately understood with more confidences. Moreover, CT and MRI are highly accurate in localization of uncommon adrenal masses, and useful to guide surgical treatments.

To elucidate the physiological importance of neuronal (N)-type calcium channels in sympathetic controls, we analyzed N-type channel-deficient (NKO) mice. Immunoprecipitation analysis revealed increased interaction between beta3 (a major accessory subunit of N-type channels) and R-type channel-forming CaV2.3 in NKO mice. R-R intervals in NKO ECG recordings were elongated and fluctuating, suggesting disturbed sympathetic tonus. N-type channel inhibitors elongated the R-R interval in control mice, whereas R-type channel blocking with SNX-482 significantly affected NKO but not control mice, indicating a compensatory role for R-type channels. Echocardiography and Langendorff heart analysis confirmed a major role for R-type channels in NKO mice. Combined, our biochemical and physiological analyses strongly suggest that the remaining sympathetic tonus in NKO mice is dependent on R-type calcium channels.

Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the hypothalamus and pituitary gland. This study used adrenal gland tissue from ANXA1-null transgenic mice, in which a beta-galactosidase (beta-Gal) reporter gene was controlled by the ANXA1 promoter, and wild-type control mice to explore the potential role of ANXA1 in adrenal function. RT-PCR and Western blotting revealed strong expression of ANXA1 mRNA and protein in the adrenal gland. Immunofluorescence labeling of ANXA1 in wild-type and beta-Gal expression in ANXA1-null adrenals localized intense staining in the outer perimeter cell layers. Immunogold electron microscopy identified cytoplasmic and nuclear ANXA1 labeling in outer cortical cells and capsular cells. Exposure of adrenal segments in vitro to dexamethasone (0.1 mum, 3 h) caused an increase in the amount of ANXA1 in the intracellular compartment and attached to the surface of the cells. The N-terminal peptide ANXA1(Ac2-26) inhibited corticosterone release. Corticosterone release was significantly greater from ANXA1-null adrenal cells compared with wild type in response to ACTH (10 pm to 5 nm). In contrast, basal and ACTH-stimulated aldosterone release from ANXA1-null adrenal cells was not different from wild type. Morphometry studies demonstrated that ANXA1 null adrenal glands were smaller than wild-type, and the cortical/medullary area ratio was significantly reduced. These results suggest ANXA1 is a regulator of adrenocortical size and corticosterone secretion.

The Vav family is a group of signal transduction molecules that activate Rho/Rac GTPases during cell signaling. Experiments using knockout mice have indicated that the three Vav proteins present in mammals (Vav1, Vav2, and Vav3) are essential for proper signaling responses in hematopoietic cells. However, Vav2 and Vav3 are also highly expressed in nonhematopoietic tissues, suggesting that they may have additional functions outside blood cells. Here, we report that this is the case for Vav2, because the disruption of its locus in mice causes tachycardia, hypertension, and defects in the heart, arterial walls, and kidneys. We also provide physiological and pharmacological evidence demonstrating that the hypertensive condition of Vav2-deficient mice is due to a chronic stimulation of the renin/angiotensin II and sympathetic nervous systems. Together, these results indicate that Vav2 plays crucial roles in the maintenance of cardiovascular homeostasis in mice.

Chromogranin A (CgA) may be critical for secretory granule biogenesis in sympathoadrenal cells. We found that silencing the expression of CgA reduced the number of secretory granules in normal sympathoadrenal cells (PC12), and we therefore questioned whether a discrete domain of CgA might promote the formation of a regulated secretory pathway in variant sympathoadrenal cells (A35C) devoid of such a phenotype. The secretory granule-forming activity of a series of human CgA domains labeled with a hemagglutinin epitope, green fluorescent protein, or embryonic alkaline phosphatase was assessed in A35C cells by deconvolution and electron microscopy and by secretagogue-stimulated release assays. Expression of CgA in A35C cells induced the formation of vesicular organelles throughout the cytoplasm, whereas two constitutive secretory pathway markers accumulated in the Golgi complex. The lysosome-associated membrane protein LGP110 did not co-localize with CgA, consistent with non-lysosomal targeting of the granin in A35C cells. Thus, CgA-expressing A35C cells showed electron-dense granules approximately 180-220 nm in diameter, and secretagogue-stimulated exocytosis of CgA from A35C cells suggested that expression of the granin may be sufficient to restore a regulated secretory pathway and thereby rescue the sorting of other secretory proteins. We show that the formation of vesicular structures destined for regulated exocytosis may be mediated by a determinant located within the CgA N-terminal region (CgA-(1-115), with a necessary contribution of CgA-(40-115)), but not the C-terminal region (CgA-(233-439)) of the protein. We propose that CgA promotes the biogenesis of secretory granules by a mechanism involving a granulogenic determinant located within CgA-(40-115) of the mature protein.

Steroidogenic acute regulatory (StAR) protein is an important regulatory protein in steroidogenesis and rapidly undergoes proteolysis after import into the mitochondria. In this study, we determined the proteolytic cleavage sites and investigated the effects on the stimulation of steroidogenic activity of the blockage of these sites by mutation. The cleaved StAR proteins, which were purified using an anti-StAR immobilized column, reacted with antiserum against the StAR C-terminal oligopeptide. The molecular weights of the purified proteins were determined by MALDI-TOF mass spectrometry, and were found to be identical to those of the 40-285 and 55-285 amino-acid-regions of the StAR protein. To confirm the identification of the cleavage sites, we constructed site-directed mutants of bovine StAR cDNA, which contained the amino acids R37A/R38A/L40A and/or R53A/R54A/R55A. These mutant StAR proteins expressed in COS-1 cells were not cleaved at positions 39-40 and 54-55, and were processed at sites different from those in the wild-type StAR protein. These mutant proteins stimulated pregnenolone formation at almost the same rate as the wild-type StAR protein in COS-1 cells, which suggests that the cholesterol transfer activity was not affected by the mutation.

The present work was undertaken in order to investigate the influence of endocrine pancreas on the adrenal gland of Triturus carnifex. Our experiments aimed at studying the effects of intraperitoneal injections of glucagon on ultrastructural morphological and morphometrical features of steroidogenic and chromaffin tissues, as well as serum levels of aldosterone, corticosterone, norepinephrine (NE) and epinephrine (E). With regard to steroidogenic tissue, in January and November, glucagon decreased lipid droplet content in steroidogenic cells, that showed clear signs of increased activity. Moreover, increased corticosteroid serum levels were found. With regard to chromaffin tissue, in January glucagon played a stimulatory role on PNMT enzyme, eliciting an increase in the presence of E granules, and a decrease in the presence of NE granules, in the chromaffin cells. Moreover, increased E serum levels and decreased NE serum levels were found. In November, glucagon gave rise to a decrease in the presence of NE and E granules in the cells; E serum levels were strongly increased, whereas NE serum levels did not undergo any significant change. These findings suggest an involvement of the endocrine pancreas of the newt in the modulation of adrenal gland activity.

Adrenal medullary chromaffin cells are derivatives of the neural crest and are widely believed to share a common sympathoadrenal (SA) progenitor with sympathetic neurons. For decades, the adrenal cortical environment was assumed to be essential for channelling SA progenitors towards an endocrine chromaffin cell fate. Our recent analysis of steroidogenic factor 1(Sf1) -/- mice, which lack an adrenal cortex, has challenged this view: in Sf1 -/- mice chromaffin cells migrate to the correct "adrenal" location and undergo largely normal differentiation. In contrast to Sf1 homozygous mutants, heterozygous animals have an adrenal cortex, which, however, is smaller than in wildtype littermates. We show here that the Sf1 +/- adrenal cortical anlagen attract normal numbers of chromaffin progenitor cells into their vicinity by embryonic day 13.5 (E13.5). Two days later, however, only a few scattered cells with highly immature features have immigrated into the adrenal cortex, whereas the remainder form a coherent cell assembly ectopically located at the medial surface of the gland. These cells appear more mature than the scattered intracortical chromaffin progenitors and express the adrenaline synthesizing enzyme PNMT with a delay of 1 day in comparison with wildtype littermates. Nevertheless, chromaffin progenitor cells undergo a numerical reduction of approximately 30% by E17.5. Together, our data suggest that normal adrenocortical development is critical for the correct immigration of chromaffin progenitors into the cortical anlagen, for the timing of PNMT expression and for the regulation of chromaffin cell numbers.

Cocaine- and amphetamine-regulated transcript peptide (CART) is constitutively expressed in discrete regions of the mammalian central and peripheral nervous system. Immunohistochemical studies reveal a well-defined network of CART-immunoreactive (irCART) neurons organized along the sympatho-adrenal axis. Sympathetic preganglionic neurons, but not parasympathetic preganglionic neurons, in the lateral horn area are CART-positive; which in turn innervate postganglionic neurons in the paravertebral and prevertebral sympathetic ganglia as well as the adrenal medulla. A population of chromaffin cells in the adrenal medulla is CART-positive; whereas, postganglionic neurons are not. Sympathetic preganglionic neurons themselves are contacted by irCART cell processes arising from neurons in the arcuate nucleus, the retrochiasmatic nucleus and the rostral ventrolateral medulla. Results from several recent studies suggest CART directly excites neurons along the sympathetic neural axis or indirectly by potentiating the action of glutamate on NMDA receptors, as evidenced by an elevation of blood pressure and heart rate following intracerebroventricular, intracisternal or intrathecal administration of the peptide to anesthetized rats or conscious rabbits.

Intravascular large B-cell lymphoma (IVLL) is a rare subtype of extranodal diffuse large B-cell lymphoma and is very difficult to diagnose in patients antemortem due to nonspecific presentation of the disease. We report a case of IVLL in a 68-year-old white female who presented with 3-month history of fever of unknown origin (FUO), night sweat, and weight loss. Laboratory tests revealed bilateral adrenal enlargement and adrenal insufficiency. IVLL was diagnosed only at autopsy. A review of the English language medical literature indicates that it is not uncommon for IVLL presented initially with FUO, bilateral adrenal enlargement, and adrenal insufficiency. We present this case to call for heightened awareness of the possibility of IVLL, particularly in an elderly woman who presents with FUO, bilateral adrenal enlargement, and adrenal insufficiency. The pathophysiologic mechanisms of adrenal insufficiency in IVLL are also discussed.

Suppression of adrenocorticotropic hormone results in reduced adrenal steroid output, adrenocortical cell atrophy, and apoptosis in young rats. To verify such effects during aging, dexamethasone was injected into rats for 3 days at five different ages; at day 4, adrenals and blood were collected for morphologic and corticosterone assay. Adrenal structure was similar at all ages, but in dexamethasone-injected animals there were ultrastructural features of apoptosis and a higher percentage of TUNEL and caspase-3-labeled nuclei and cytoplasm; their corticosterone decreased significantly. In both groups, there was age-related decrease in the percentage of apoptotic cells, significant only in dexamethasone-injected rats. The data suggest that aged adrenocortical cells are less susceptible to the lack of adrenocorticotropic hormone (ACTH), possibly as a result of their decreased functional ability.

The aims of this study were to propose a bioindicator organism, the newt Triturus carnifex, for the assessment of toxicological impact of thiophanate methyl in the Campania region (Italy) and the possible adverse activity on the adrenal gland. In the acute toxicity study, experimental groups of T. carnifex were exposed to 2.40, 4.80, 9.60 and 19.20 microg/L tap water of thiophanate methyl for 2 days; the LD50 was found to be 9.60 microg/L. To evaluate the effects on the adrenal gland, newts were exposed to a dose of 25% of the LD50 2 days for 8 days. The ultrastructural features of the tissues as well as the serum levels of aldosterone, corticosterone, norepinephrine (NE) and epinephrine (E) were evaluated. The number of secretory vesicles in the chromaffin cells appeared significantly decreased, whereas NE and E serum levels appeared strongly increased. Moreover, corticosterone and aldosterone serum levels appeared significantly reduced. The results suggest that: 1) T. carnifex has the features of an ideal bioindicator, due to its high sensitivity to thiophanate methyl, 2) thiophanate methyl acts as endocrine disruptor, affecting the adrenal gland at very low doses, 3) thiophanate methyl may be toxic for nontarget organisms, such as newts.

Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.

Using light, electron microscopy and cytochemistry, the early (embryonic week 4-8) stages of adrenal gland (AG) development were studied in domestic pig. The interrelations between the cells of the fetal cortex (FC) and chromaffin cells (CC) were traced. At week 5, AG primordium is represented by FC, which consists of the epithelioid cells, with the ingrowing neural cords containing CC islets. Starting at the early embryonic period and up to fetal period, CC and interrenal cells of FC are closely interrelated with each other and sinusoidal capillaries. Both cellular types are at different stages of differentiation, including the functionally active elements. At weeks 7-8, FC cells undergo involution, while those ones, left at periphery, form definitive cortex. CC are located in the central part of the organ and form suprarenal tissue. Authors hypothesize, that CC, migrating into AG primordium, initially induce the development of interrenal primordium, and later cause the involution of FC. This, possibly, may be explained by the fact that further antenatal and postnatal development of the organism requires more corticosteroids than the amount produced by FC.

The normal adrenal glands can be detected by high-resolution-sonography in a high percentage of cases. Sonography is also highly sensitive in the diagnosis of tumours of the adrenal glands. Only some of those tumours are hormonally active. Amongst the benign tumours, adenomas are the most frequent (up to 8%). Pheochromocytomas are less frequent (4.8% in uFNB statistics). Amongst the malignant tumours, metastases are more frequent than primary carcinomas (32.5% vs. 19.8% in uFNB-statistics). The adrenal glands are the fourth most common location of metastases. Bronchiogenic carcinomas, malignant melanomas, carcinomas of the breast and stomach as well as renal carcinomas metastasize into the adrenals most often. Much less frequent are infiltrates of lymphomas in adrenal glands tumours (3.4%). Incidentalomas are accidentally detected tumours of the adrenal glands without clinical symptoms. Malignant tumours only represent a very small part of incidentalomas (0.2%). They seldom show hormonal activity. In the case of an accidentally detected tumour, we propose a minimal laboratory profile (24-h-urinary-catecholamines, dexamethasone-test, electrolyte metabolism). The uFNB of the adrenal glands has a high sensitivity (90-95%). Complications are rare (pneumothorax, bleeding, pain; approximately 3%). Biopsy of pheochromocytomas (2-4% malignant) is dangerous because of the risk of provoking a hypertensive crisis. Case studies have been published about this problem. On the other hand, numerous cases of uncomplicated biopsies have also been published. Considering the excellent imaging methods and laparoscopic surgery methods on hand, the indication of FNP is restricted to the following cases: 1. the presence of a metastasis leading to therapeutical consequences; 2. suspected lymphoma 3. undefined lesion (3-5 cm), hormonally inactive, without typical signs of a tumour 4. patients refusing surgery. 5. uFNB in case of tumours of undefined dignity is only justified in specific cases. Recommendations for this procedure in accidentally detected tumours of the adrenal glands: < 3 cm and hormonally inactive --> US-follow up, > 5 cm + suspected tumour --> surgery, 3-5 cm uFNB after laboratory diagnostics.

Given the importance of inositol 1,4,5-trisphosphate receptor (IP(3)R)/Ca(2+) channels in the control of intracellular Ca(2+) concentrations, we determined the relative concentrations of the IP(3)R isoforms in subcellular organelles, based on serially sectioned electron micrographs. The endoplasmic reticulum (ER) was estimated to contain 15-20% of each of the three IP(3)R isoforms while secretory granules contained 58-69%. The nucleus contained approximately 15% each of IP(3)R-1 and -2, but 25% of IP(3)R-3, whereas the plasma membrane contained approximately 1% or less of each. These suggested that secretory granules, the nucleus and ER are at the center of IP(3)-dependent intracellular Ca(2+) control mechanisms in chromaffin cells.

This study provides the first detailed description of the Atlantic bottlenose dolphin (Tursiops truncatus) adrenal gland with emphasis on the medulla. Thirty-one dolphins of varying age and sex were used in this study. No statistical differences were found between the right and left gland mass, however, the left was typically greater. Mean mass for the right and left adrenal glands were 4.99 +/- 0.513 and 5.36 +/- 0.558 g, respectively. No statistical differences were found between average gland mass and sexual maturity or sex. The average cortex/medulla ratio was 1.22 +/- 0.060 meaning approximately 48% is cortex, 41% is medulla, and 11% was categorized as other (i.e. blood vessels, connective tissue, etc.). The cortex contained pseudolobules and the typical zonation. A medullary band, consisting of highly basophilic staining cells was found at the periphery of the medulla. Projections of the medulla to the gland capsule were noted. Immunolabelling with polyclonal antibodies against the enzymes dopamine beta hydroxylase and phenylethanolamine N-methyl transferase indicated that noradrenaline producing cells are found throughout the medulla including the medullary band while adrenaline producing cells are only found within the medullary band. Transmission electron microscopy confirmed the presence of two distinct cell populations within the medullary band and a single cell population throughout the medulla.