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Adrenal Cortex (adrenal + cortex)
Selected AbstractsIdentification of a 250 kDa putative microtubule-associated protein as bovine ferritinFEBS JOURNAL, Issue 3 2005Evidence for a ferritin, microtubule interaction We reported previously on the purification and partial characterization of a putative microtubule-associated protein (MAP) from bovine adrenal cortex with an approximate molecular mass of 250 kDa. The protein was expressed ubiquitously in mammalian tissues, and bound to microtubules in vitro and in vivo, but failed to promote tubulin polymerization into microtubules. In the present study, partial amino acid sequencing revealed that the protein shares an identical primary structure with the widely distributed iron storage protein, ferritin. We also found that the putative MAP and ferritin are indistinguishable from each other by electrophoretic mobility, immunological properties and morphological appearance. Moreover, the putative MAP conserves the iron storage and incorporation properties of ferritin, confirming that the two are structurally and functionally the same protein. This fact led us to investigate the interaction of ferritin with microtubules by direct electron microscopic observations. Ferritin was bound to microtubules either singly or in the form of large intermolecular aggregates. We suggest that the formation of intermolecular aggregates contributes to the intracellular stability of ferritin. The interactions between ferritin and microtubules observed in this study, in conjunction with the previous report that the administration of microtubule depolymerizing drugs increases the serum release of ferritin in rats [Ramm GA, Powell LW & Halliday JW (1996) J Gastroenterol Hepatol11, 1072,1078], support the probable role of microtubules in regulating the intracellular concentration and release of ferritin under different physiological circumstances. [source] Identification of the rat adrenal zona fasciculata/reticularis specific protein, inner zone antigen (IZAg), as the putative membrane progesterone receptorFEBS JOURNAL, Issue 7 2001Farah S. Raza Using immunological methods, a protein specific to the inner zones of the rat adrenal cortex, and called inner zone antigen (IZAg), was previously shown to have two interrelated forms of 26 kDa (IZAg1) and 55,60 kDa (IZAg2), and to have an action on steroid hydroxylation. After two-dimensional gel electrophoresis, and immunoaffinity column purification, N-terminal amino-acid analysis showed that the first 12 amino acids were identical to those of a recently described putative membrane located progesterone receptor (PPMR). RT-PCR was then used to generate the cDNA of this protein, using RNA extracted from rat adrenals. A glutathione S-transferase (GST)-fusion construct was expressed in Escherichia coli, and shown to generate an immunoreactive product of molecular mass consistent with its identification as IZAg1. More detailed examination of the distribution of this protein, not only in the zona fasciculata/reticularis of the adrenal cortex, but also in the Leydig cell, kidney and liver, suggest it may have a role in steroid hormone synthesis and/or metabolism. [source] Human CYP11A1 promoter drives Cre recombinase expression in the brain in addition to adrenals and gonadsGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2007Hsu-Shui Wu Abstract The first step of steroid biosynthesis is catalyzed by cytochrome P450scc, encoded by CYP11A1. To achieve steroidogenic tissue-specific inactivation of genes in vivo by the Cre-loxP approach, we used the 4.4-kb regulatory region of the human CYP11A1 gene to drive Cre recombinase expression in the tissues that produce steroids. The resulting SCC-Cre mice express high levels of Cre in the adrenal cortex and gonads at the same sites as that for the endogenous CYP11A1 expression. In addition, Cre activity was found in the diencephalon and midbrain. In the developing brain, the Cre activity was first detected in the embryonic day 10.5. Our study is the first to show that the 4.4-kb CYP11A1 promoter is transcriptionally active in the brain in vivo. genesis 45:59,65, 2007. © 2007 Wiley-Liss, Inc. [source] Conditional gene recombination by adenovirus-driven Cre in the mouse uterusGENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT, Issue 2 2006Haibin Wang Abstract Cre-mediated conditional gene targeting has been shown to be successful in many cell and tissue types. However, gene recombination in the uterus with heterogeneous cell types by Cre activation is not yet well established. Using recombinant adenoviruses expressing a functional Cre (ADV-Cre) and ROSA26 reporter mice, we show here that ADV-Cre infused intraluminally in a small volume (10 ,l) conditionally excises the loxP site, resulting in lacZ expression in uterine luminal epithelial cells without significantly affecting pregnancy. In contrast, a similar intraluminal infusion of ADV-Cre in a larger volume (50 ,l) damages the normal architecture and integrity of the luminal epithelium, inducing gene recombination in the underneath stromal cells, with disruption of pregnancy. Further, decidualizing stromal cells at the implantation sites can be targeted by ADV-Cre after intravenous administration on days 5,6. This route of administration also elicits Cre activity in other tissues, including the liver, spleen, ovary, and, more remarkably, in the adrenal cortex. These findings demonstrate the feasibility of achieving conditional expression or deletion of specific genes in uterine cells at desired times and physiological states. genesis 44:51,56, 2006. © 2006 Wiley-Liss, Inc. [source] Adrenal toxicology: a strategy for assessment of functional toxicity to the adrenal cortex and steroidogenesisJOURNAL OF APPLIED TOXICOLOGY, Issue 2 2007Philip W. Harvey Abstract The adrenal is the most common toxicological target organ in the endocrine system in vivo and yet it is neglected in regulatory endocrine disruption screening and testing. There has been a recent marked increase in interest in adrenal toxicity, but there are no standardised approaches for assessment. Consequently, a strategy is proposed to evaluate adrenocortical toxicity. Human adrenal conditions are reviewed and adrenocortical suppression, known to have been iatrogenically induced leading to Addisonian crisis and death, is identified as the toxicological hazard of most concern. The consequences of inhibition of key steroidogenic enzymes and the possible toxicological modulation of other adrenal conditions are also highlighted. The proposed strategy involves an in vivo rodent adrenal competency test based on ACTH challenge to specifically examine adrenocortical suppression. The H295R human adrenocortical carcinoma cell line is also proposed to identify molecular targets, and is useful for measuring steroids, enzymes or gene expression. Hypothalamo-pituitary-adrenal endocrinology relevant to rodent and human toxicology is reviewed (with an emphasis on multi-endocrine axis effects on the adrenal and also how the adrenal affects a variety of other hormones) and the endocrinology of the H295R cell line is also described. Chemicals known to induce adrenocortical toxicity are reviewed and over 60 examples of compounds and their confirmed steroidogenic targets are presented, with much of this work published very recently using H295R cell systems. In proposing a strategy for adrenocortical toxicity assessment, the outlined techniques will provide hazard assessment data but it will be regulatory agencies that must consider the significance of such data in risk extrapolation models. The cases of etomindate and aminoglutethimide induced adrenal suppression are clearly documented examples of iatrogenic adrenal toxicity in humans. Environmentally, sentinel species, such as fish, have also shown evidence of adrenal endocrine disruption attributed to exposure to chemicals. The extent of human sub-clinical adrenal effects from environmental chemical exposures is unknown, and the extent to which environmental chemicals may act as a contributory factor to human adrenal conditions following chronic low-level exposures will remain unknown unless purposefully studied. Copyright © 2007 John Wiley & Sons, Ltd. [source] Intracrine androgenic apparatus in human bone marrow stromal cellsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 9b 2009Tarvo Sillat Abstract It was suggested that human mesenchymal stromal cells might contain an intracrine enzyme machinery potentially able to synthesize the cell's own supply of dihydrotestosterone (DHT) from dehydroepiandrosterone (DHEA) pro-hormone produced in the adrenal cortex in the reticular zone, which is unique to primates. Indeed, 3,-hydroxysteroid dehydrogenase (3,-HSD) and 5,-reductase enzyme proteins were expressed in resting mesenchymal stromal cells (MSCs) in vitro. However, the ,bridging' enzymes 17,-HSDs, catalysing interconversion between 17,-ketosteroids and 17,-hydroxysteroids, were not found in resting MSCs, but 17,-HSD enzyme protein was induced in a dose-dependent manner by DHEA. Quantitative real-time polymerase chain reactions disclosed that this was mainly due to induction of the isoform 5 catalysing this reaction in ,forward', androgen-bound direction (P < 0.01). This work demonstrates that the MSCs have an intracrine machinery to convert DHEA to DHT if and when challenged by DHEA. DHEA as substrate exerts a positive, feed-forward up-regulation on the 17,-hydroxy steroid dehydrogenase-5, which may imply that DHEA-DHT tailor-making in MSCs is subjected to chronobiological regulation. [source] Synthesis and biological evaluation of [carboxyl - 11C]eprosartanJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 8 2009Ola Ĺberg Abstract Essential hypertension occurs in approximately 25% of the adult population and one cause of hypertension is primary aldosteronism. Targeting the angiotensin II AT1 receptor using PET and an appropriate tracer may offer a diagnostic method for adrenocortical tissue. This report describes the synthesis of the selective AT1 receptor antagonist [carboxyl - 11C]eprosartan 10, 4-[2-butyl-5-((E)-2-carboxy-3-thiophen-2-yl-propenyl)-imidazol-1-ylmethyl]-[carboxyl - 11C]benzoic acid, and its precursor (E)-3-[2-butyl-3-(4-iodo-benzyl)-3H -imidazol-4-yl]-2-thiophen-2-ylmethyl-acrylic acid 9. 11C-carboxylation of the iodobenzyl moiety was performed using a palladium-mediated reaction with [11C]carbon monoxide in the presence of tetra- n -butyl-ammonium hydroxide in a micro-autoclave using a temperature gradient from 25 to 140°C over 5,min. After purification by semipreparative HPLC, [carboxyl - 11C]eprosartan 10 was obtained in 37,54% decay-corrected radiochemical yield (from [11C]carbon monoxide) with a radiochemical purity >95% within 35,min of the end of bombardment (EOB). A 5-µAh bombardment gave 2.04,GBq of 10 (50% rcy from [11C]carbon monoxide) with a specific activity of 160,GBq,µmol,1 at 34,min after EOB. Frozen-section autoradiography shows specific binding in kidney, lung and adrenal cortex. In vivo experiments in rats demonstrate a high accumulation in kidney, liver and intestinal wall. Copyright © 2009 John Wiley & Sons, Ltd. [source] Circadian and age-related changes in stress responsiveness of the adrenal cortex and erythrocyte antioxidant enzymes in female rhesus monkeysJOURNAL OF MEDICAL PRIMATOLOGY, Issue 5 2008Nadezhda D. Goncharova Abstract Background, The objective of this study was to evaluate the role of the adrenal cortex in the regulation of antioxidant enzyme defense and to characterize this regulation in different age periods. Methods, Five young and five old female rhesus monkeys were subjected to 2 hours squeeze cage restraint stress at 0900 or 1500 hours. Plasma levels of corticosteroids and activities of erythrocyte antioxidant enzymes were measured before the stress and 30, 60, 120, 240 minutes after beginning of the stress. Results, Young monkeys showed a circadian rhythm in stress responsiveness as measured by corticosteroids and glutathione reductase. The rhythm was attenuated in old animals. Age-related changes in the overall level of response to the afternoon stress were also seen in the corticosteroid and glutathione reductase measures. Conclusions, The study demonstrated that corticosteroids play an essential role in the regulation of antioxidant enzyme defense in stress conditions and that the reliability of their regulation decreases with age. [source] Nongenomic Actions of Adrenal Steroids in the Central Nervous SystemJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2010N. K. Evanson Mineralocorticoids and glucocorticoids are steroid hormones that are released by the adrenal cortex in response to stress and hydromineral imbalance. Historically, adrenocorticosteroid actions are attributed to effects on gene transcription. More recently, however, it has become clear that genome-independent pathways represent an important facet of adrenal steroid actions. These hormones exert nongenomic effects throughout the body, although a significant portion of their actions are specific to the central nervous system. These actions are mediated by a variety of signalling pathways, and lead to physiologically meaningful events in vitro and in vivo. We review the nongenomic effects of adrenal steroids in the central nervous system at the levels of behaviour, neural system activity, individual neurone activity and subcellular signalling activity. A clearer understanding of adrenal steroid activity in the central nervous system will lead to a better ability to treat human disease as well as reduce the side-effects of the steroid treatments already in use. [source] Glucocorticoid regulation of the inflammatory response to injuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2004M. P. Yeager During the first half of the 20th century, physiologists were interested in the adrenal glands primarily because adrenalectomized animals failed to survive even mild degrees of systemic stress. It eventually became clear that hormones secreted by the adrenal cortex were critical for survival and, in this context, adrenal cortical hormones were widely considered to support or stimulate important responses to stress or injury. With the purification and manufacture of adrenal cortical hormones in the 1930s and 1940s, clinicians suddenly discovered the potent anti-inflammatory actions of glucocorticoids (GCs). This dramatic, and unexpected, discovery has dominated clinical and laboratory research into GC actions throughout the second half of the 20th century. More recent research is again reporting GC-induced stimulatory effects on a variety of inflammatory response components. These effects are usually observed at low GC concentrations, close to concentrations that are observed in vivo during basal, unstimulated states. For example, GC-mediated stimulation has been reported for the hepatic acute-phase response, for cytokine secretion, expression of cytokine/chemokine receptors, and for the pro-inflammatory mediator, macrophage migration inhibition factor. It seems clear that the long-held clinical view that GCs act solely as anti-inflammatory agents needs to be re-assessed. Varying doses of GCs do not lead simply to varying degrees of inflammation suppression, but rather GCs can exert a full range of effects from permissive to stimulatory to suppressive. [source] ACTH and adrenocortical gap junctionsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 3 2003Sandra A. Murray Abstract Since the initial identification of gap junctions in the adrenal gland, it has been proposed that a system involving direct cell,cell communication might be involved in adrenal cortical functions. Gap junction channels do, in fact, provide pathways for direct intercellular exchange of small molecules (<1,000 Da), many of which have the potential to influence a wide range of cellular activities. Gap junctions are composed of proteins called connexin which, in the adrenal cortex, have proven to be remarkably consistent in both type and zonal distribution with connexin 43 (Cx43) as the predominant component in mammalian adrenal glands thus far evaluated. Only the inner two zones of the cortex (zonae fasciculata and reticularis) exhibit significant amounts of Cx43 and functional coupling. Adrenocorticotropin (ACTH) has been shown to increase Cx43 protein in vivo and in vitro, and a strong correlation has been noted between the presence of gap junctions and certain adrenal cortical functions, especially steroidogenic capacity and cell proliferation. This review summarizes evidence of the Cx43 expression in adrenal cortical cells and the likely role of Cx43 in steroidogenesis and cell proliferation. It is concluded that control of gap junction expression in the adrenal gland is hormonally dependent and is functionally linked to adrenal gland zonation. Microsc. Res. Tech. 61:240,246, 2003. © 2003 Wiley-Liss, Inc. [source] Molecular Reproduction & Development: Volume 77, Issue 6, Cover imageMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 6 2010Article first published online: 21 APR 2010 This adrenal section shown was taken from a 1 year-old mouse lacking Sonic hedgehog (Shh) in the steroidogenic factor-positive adrenal cortical cells during fetal life. Lack of Shh did not affect formation of the cortex (magenta, positive for 3beta-HSD) and medulla (green, positive for tyrosine hydroxylase). However, the mutant adrenal cortex underwent hypoplasia and hypertrophy with age. The section was counterstained with the nuclear dye DAPI (blue). See the accompanying review by Huang and Yao in this issue. [source] Adrenal rest tumor of the liver: A case report with immunohistochemical investigation of steroidogenesisPATHOLOGY INTERNATIONAL, Issue 3 2000Kazumori Arai Abstract A case of adrenal rest tumor arising in the liver of a 62-year-old male with chronic hepatitis type C is reported. The tumor was clinically non-functioning and required distinction from hepatocellular carcinoma. The yellowish,brown tumor measured 25 × 18 × 15 mm and was located in the subcapsular portion of the right hepatic lobe. Histologically, the tumor presented features similar to those of the adrenal cortex and was predominantly composed of pale cells. Electron micrograph revealed lipid droplets and mitochondria with tubulo,vesicular cristae, consistent with the characteristics of steroid-producing cells. Immunohistochemically, the tumor expressed the adrenal 4 binding protein and a number of enzymes involved in the synthesis of adrenocortical steroids. At surgery, the right adrenal gland was present independently from the liver. This hepatic tumor was considered to be an adrenal rest tumor with steroidogenic capability. [source] Prenatal synthetic glucocorticoid exposure alters hypothalamic,pituitary,adrenal regulation and pregnancy outcomes in mature female guinea pigsTHE JOURNAL OF PHYSIOLOGY, Issue 5 2010Elizabeth Dunn Preterm delivery occurs in approximately 10% of all pregnancies. Prenatal exposure to synthetic glucocorticoids (sGCs) reduces the incidence of respiratory distress syndrome (RDS) in these babies. Therefore, administration of multiple courses of sGCs became common practice. Animal and human studies have demonstrated that multiple courses of sGCs can have long-term effects. While the majority of animal studies have been undertaken in male offspring, it is emerging that there are profound sex differences in the consequences of prenatal sGC exposure. To our knowledge, no studies have determined the effects of prenatal sGC exposure on hypothalamic,pituitary,adrenal (HPA) axis function in female offspring while accounting for reproductive cycle status, or determined if there are effects on pregnancy parameters. Pregnant guinea pigs were administered three courses of betamethasone (Beta), dexamethasone (Dex) or vehicle on gestational days 40/41, 50/51 and 60/61. In adulthood (age range: postnatal days 126,165), basal and activated HPA axis function were assessed at various stages of the reproductive cycle. The female offspring were then mated and underwent an undisturbed pregnancy. Females were killed in the luteal phase of the reproductive cycle following litter weaning, and molecular analysis undertaken. In the luteal phase, Beta-exposed females exhibited significantly lower basal salivary cortisol levels (P < 0.05). Dex-exposed females also exhibited significantly lower basal salivary cortisol levels during the luteal phase (P < 0.05), but increased basal salivary cortisol levels during the ostrous phase (P < 0.01). The Beta-exposed females exhibited increased glucocorticoid receptor (GR) mRNA expression in the CA1/2 region of the hippocampus (P < 0.05) and MC2R mRNA in the adrenal cortex (P < 0.05). The Dex-exposed animals exhibited higher hippocampal GR and mineralocorticoid receptor (MR) mRNA levels (P < 0.05). Beta-exposed females showed reduced fecundity (P < 0.05). In Dex-exposed females there was a lower male to female sex ratio. In conclusion, prenatal sGC exposure affects HPA axis activity, in a cycle-dependent manner, and long-term reproductive success. The clinical implications of the findings on endocrine function and pregnancy in females are profound and further follow-up is warranted in human cohorts. Furthermore, we have shown there are considerable difference in phenotypes between the Beta- and Dex-exposed females and the specific endocrine and maternal outcome is contingent on the specific sGCs administered during pregnancy. [source] Modulation of body fluids and angiotensin II receptors in a rat model of intra-uterine growth restrictionTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Sophie Bédard We previously reported that sodium restriction during pregnancy reduces plasma volume expansion and promotes intra-uterine growth restriction (IUGR) in rats while it activates the renin,angiotensin,aldosterone system (RAAS). In the present study, we proceeded to determine whether expression of the two angiotensin II (ANGII) receptor subtypes (AT1 and AT2) change in relation to maternal water,electrolyte homeostasis and fetal growth. To this end, pregnant (gestation day 15) and non-pregnant Sprague-Dawley rats were randomly assigned to two groups fed either normal, or Na+ -restricted diets for 7 days. At the end of the treatment period, plasma aldosterone and renin activity as well as plasma and urine electrolytes were measured. Determinations for AT1 and AT2 mRNA and protein were made by RNase protection assay and photoaffinity labelling, respectively, using a number of tissues implicated in volume regulation and fetal growth. In non-pregnant rats, Na+ restriction decreases Na+ excretion without altering plasma volume, plasma Na+ concentration or the expression of AT1 and AT2 mRNA or protein in the tissues examined. In normally fed pregnant rats when compared to non-pregnant controls, AT1 mRNA increases in the hypothalamus as well as pituitary and declines in uterine arteries, while AT1 protein decreases in the kidney and AT2 mRNA declines in the adrenal cortex. In pregnant rats, Na+ restriction induces a decrease in plasma Na+, an increase in plasma urea, as well as a decline in renal urea and creatinine clearance rates. Protein levels for both AT1 and AT2 in the pituitary and AT2 mRNA in the adrenal cortex are lower in the Na+ -restricted pregnant group when compared to normally fed pregnant animals. Na+ restriction also induces a decrease in AT1 protein in the placenta. In conclusion, these results suggest that pregnancy may increase sensitivity to Na+ depletion by the tissue-specific modulation of ANGII receptors. Finally, these receptors may be implicated in the IUGR response to low Na+. [source] Histological Structure of the Adrenal Gland of the Bottlenose Dolphin (Tursiops truncatus) and the Striped Dolphin (Stenella coeruleoalba) from the Adriatic SeaANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 1 2010S. Vukovi Summary The structure of the adrenal gland was studied in 11 bottlenose dolphins (Tursiops truncatus), and five striped dolphins (Stenella coeruleoalba). These species are legally protected in Croatia. All examined animals died of natural causes and were found stranded along eastern Adriatic coast. In both species the adrenal gland consists of a cortex and a medulla; the cortex is divided into three zones. Whereas in the bottlenose dolphin, there is a zona arcuata which contains columnar cells arranged in the form of arches; in the striped dolphin this zone is replaced by zona glomerulosa containing rounded clusters of polygonal cells. In both species, the zona fasciculata consists of radially oriented cords of polygonal cells, whereas in zona reticularis cells are arranged in branching and anastomosing cords. The adrenal medulla in both species contains dark, epinephrine-secreting cells and light norepinephrine-secreting cells. Epinephrine-secreting cells are localized in the outer part of the medulla, whereas norepinephrine-secreting cells are found in the inner part, arranged in clusters and surrounded by septa of thin connective tissue. The gland is surrounded by a thick connective-tissue capsule, from where thick trabeculae extend towards the interior. In the bottlenose dolphin, group of cells resembling both medullar and cortical cells can be seen within the capsule; whereas only groups of cells resembling cortical cells are found within the capsule of the striped dolphin. In the bottlenose dolphin invagination of the adrenal cortex into the medulla is obvious as well as medullary protrusions extending through cortex to the connective tissue capsule. [source] Tissue Distribution of P-Glycoprotein in CatsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 6 2009S. Van Der Heyden Summary Permeability glycoprotein (P-gp) is a membrane-bound efflux pump that exports various substances out of the cell. Variations in P-gp expression play an important role in susceptibility to toxic substances, drug efficacy and disease risk. In the present study, the distribution of the MDR1 -gene product P-gp was determined in normal tissues of domestic shorthair cats using immunohistochemistry. Two monoclonal antibodies C494 and C219 were used, recognizing a different epitope on the human P-gp molecule. A consistent positive immunolabelling was obtained. The tissue distribution and cellular locations with antibody C494 were similar to those in man and dogs; with liver, colon, adrenal cortex and brain capillaries being consistently and intensely labelled. However, the immunolabelling in the kidney was in contradiction to man and dogs. The C219 antibody seems to react with a specific form of P-gp, only expressed in feline tissues with a barrier function, i.e. endothelia of the brain, testes and ovaries, and intestinal epithelial cells in contact with the lumen. [source] On the Structure of the Adrenal Gland of the Common Seal (Phoca vitulina vitulina)ANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 5 2004H. Bragulla Summary The adrenal gland is a vitally important endocrine gland that occupies a central role in the regulatory mechanisms of the body metabolism. Environmental stress factors lead to permanent strain and overload of the body resulting in structural alterations of the adrenals that in turn are followed by hormonal imbalances. This leads to an increased susceptibility to bacterial and viral diseases. The recurrence of numerous fatalities in the different seal populations of the North Sea (during the years 1988, 1989 and 2002), of the Baikal Lake and Caspian Sea (during the years 2000 and 2001) were the motive for a morphological investigation of the species-specific structure of the adrenal gland of the common seal in order to differentiate environmental stress-induced pathological alterations from the physiological structure of this organ. The study was based on adrenals of 112 common seals (Phoca vitulina vitulina) using light microscopic and transmission and scanning electron microscopic methods. The phocine adrenal gland displays several structural characteristics. Originating from the connective tissue organ capsule, narrow and broad septa intersperse the adrenal cortex. These septa contain blastemata as a reserve for the regeneration of hormone-producing cortical cells. Such blastemata are also occurring in the form of an intermediate zone in between the zona glomerulosa and zona fasciculata in the phocine adrenal cortex. Another species-specific characteristic is an inverse part of the adrenal cortex encircling the central vein of the organ. These structural features have to be considered in assessment and definition of pathological alterations of the adrenals as observed in the form of exhausted blastema cell pools in the adrenocortex of seals perished in the mentioned phocine mass mortalities. [source] Adrenocorticotropic hormone-induced secretion of cortisol in goats is inhibited by androgenANIMAL SCIENCE JOURNAL, Issue 1 2006Yuko MAEJIMA ABSTRACT In a previous study, it was found that there are sex differences in goats with respect to the levels of cortisol secretion induced by transportation stress. We also found that treatment of castrated male goats with dihydrotestosterone (DHT) suppressed the increase in plasma cortisol concentration following transportation, but did not suppress the secretion of adrenocorticotropic hormone (ACTH). This suggests that androgen might block ACTH - induced cortisol secretion. In order to examine this hypothesis, the effects of androgen on ACTH-induced cortisol secretion in goats were investigated. First, castrated male goats were treated with testosterone (T), DHT or cholesterol (cho) for 21,25 days. Cho was used as a control for T and DHT treatment. Then, plasma cortisol concentrations were compared among the hormonal treatments after ACTH injection. Subsequently, the distribution of androgen receptors in the caprine adrenal gland was investigated. There were no differences in the basal cortisol concentrations among the hormonal treatments. However, plasma cortisol concentrations after ACTH injection were significantly lower in T - and DHT - treated goats than in cho - treated goats. Androgen receptors were present in 60% of the cells in the zonae fasciculata and reticularis of the adrenal cortex, the regions that secrete glucocorticoids. These results suggest that androgen may act directly on the adrenal cortex to suppress cortisol secretion induced by ACTH. [source] Investigational New Drug-Directed Toxicology and Pharmacokinetic Study of 4-[3-(2-Nitro-1-Imidazolyl)-Propylamino]-7-Chloroquinoline Hydrochloride (NLCQ-1, NSC 709257) in Beagle DogsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2010Maria V. Papadopoulou The present study is one of several pre-clinical toxicology studies conducted in support of an ,investigational new drug' (IND) application to test this agent as an adjuvant to radio/chemotherapy for the treatment of cancer in humans. Twenty-four dogs were each assigned to one vehicle control group or to one of three test article-treated groups (three dogs/sex/treatment group). Intravenous (i.v.) doses of 0, 2.74, 5.48 and 10.95 mg/kg/day (54.8, 109.6 or 219 mg/m2/day) were administered on a per day × 5 days (qd × 5) schedule. NLCQ-1 was formulated as a solution in sterile saline at 1.5 mg/ml. None of the dogs died during this 33-day study. With few exceptions, most of the clinical signs of toxicity were noted within 2 hr following dosing in the 10.95 mg/kg/day dose group. These observations included aggressive behaviour, ataxia, tachypnea, emesis, hypoactivity, excessive salivation, tremors, and involuntary urination and defecation. Aggressive behaviour was judged to be dose-limiting. No clinical signs of toxicity were noted during the 28-day observation period that followed the 5-day dose period. Findings in a functional observation battery examination were consistent with the clinical observations. No drug-related effects were noted on the body weight or food consumption values, and no drug-related changes were noted during ocular examinations made on these animals prior to scheduled necropsy or during examination of electrocardiogram recordings made at 15 min. and 2 hr after dosing on days 1 and 5. No definitive changes in haematology, clinical chemistry or coagulation values were noted in dogs treated with NLCQ-1. NLCQ-1 was detected in the plasma of treated dogs on days 1 and 5, up to 60 min. after dosing (2.74 and 5.48 mg/kg/day) and up to 8 hr after dosing (10.95 mg/kg/day). There was a dose-related increase in maximum plasma concentration of NLCQ-1 at 5 min. after dosing; comparable concentrations were noted on days 1 and 5. No definitive test article-related lesions were noted during microscopic evaluation of tissues from dogs in this study, although lesions noted at the injection site and in the vascular tissue, lungs, thymus, prostate gland, muscle, adrenal cortex and tongue may have resulted from treatment with this drug. Any drug-related toxicity noted was readily reversible and not cumulative. No sex difference was detected in the susceptibility to NLCQ-1-induced toxicity. [source] Disorders of the human adrenal cortexACTA PAEDIATRICA, Issue 9 2009Anna Wedell No abstract is available for this article. [source] An enigmatic eye: the histology of the tuatara pineal complexCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 6 2004Casey Y-J Ung MB BS (Qld) Abstract Aim: To examine the histology of the tuatara pineal complex and to compare findings wtih those of Dendy. Some reptiles have an anatomically sophisticated pineal complex with a median pineal eye, a paraphysis and a pineal sac. In comparison, the human pineal gland is simple and homogenous and thought to be a phylogenetic relic. It is now considered a neuroendocrine gland the function of which is still not fully understood. Its simple anatomical structure is in contrast to its biochemical complexity; its secretions (the most studied being melatonin) modifying the function of the adeno- and neurohypophysis, thyroid and parathyroids, adrenal cortex and medulla, endocrine pancreas and the gonads. Methods: Histological sections of the brain of a neonatal tuatara were studied by light microscopy. Results: The histological findings of the pineal eye demonstrated a cornea-like structure, rudimentary lens and simple retina. The adjacent paraphysis was a large, multisaccular organ and the pineal sac a very large saccular organ with a poorly differentiated retina. Conclusion: The pineal eye of the tuatara has a remarkably eye-like structure with photoreceptors that in other reptiles have been shown to exhibit photoreceptive capabilities. The paraphysis appeared to have a secretory function that is as yet undetermined, while the pineal sac had the appearance of a poorly differentiated retina. Thus it appears that the complex biochemistry of the human pineal gland is reflected in the complex anatomical structure of this primitive reptile. [source] The role of TASK1 in aldosterone production and its expression in normal adrenal and aldosterone-producing adenomasCLINICAL ENDOCRINOLOGY, Issue 1 2010Edson F. Nogueira Summary Objectives, Aldosterone production in the adrenal glomerulosa is mainly regulated by angiotensin II and K+. Adrenal glomerulosa cells are uniquely sensitive to extracellular K+. Genetic deletion of subunits of K+ -selective leak-channels (KCNK), TASK1 and/or TASK3, in mice generates animals with hyperaldosteronism and histological changes in the adrenal cortex. Herein, we studied the expression of TASK1 in human adrenocortical cells, as well as its role in aldosterone production in H295R cells. Design, TASK1 expression was investigated by comparative microarray analysis of aldosterone-producing adenomas (APA) and normal adrenals (NAs). The effects of TASK1 knockdown by siRNA transfection were investigated in H295R cells. Fluo-4 fluorescent measurements of intracellular Ca2 + and pharmacological inhibition of Ca2 + -dependent calmodulin kinases (CaMK) were performed to better define the effects of TASK1 on Ca2 + signalling pathways. Results, Microarray analysis of APA and NA showed similar expression of TASK1 between these two groups. However, in APA, NA and H295R cells the expression of TASK1 was predominant when compared with other KCNK family members. Knockdown of TASK1 (with siRNA) induced the expression of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2), and also stimulated pregnenolone and aldosterone production. Cells transfected with siTASK1 had increased intracellular Ca2 + , leading to activation of CaMK and increased expression of CYP11B2. Conclusions, Our study reveals the predominant expression of TASK1 over other KCNK family genes in the human adrenal cortex. Herein, we also described the role of TASK1 in the regulation of human aldosterone production through regulation of intracellular Ca2 + and CaMK signalling pathways. [source] Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiencyCLINICAL ENDOCRINOLOGY, Issue 5 2008Sophie Bensing Summary Objectives, Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. Design and patients, A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964,2004. Measurements, Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). Results, A more than 2-fold increased mortality risk was observed in both women (SMR 2·9, 95% CI 2·7,3·0) and men (SMR 2·5, 95% CI 2·3,2·7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4·6, 95% CI 3·5,6·0) compared with patients with APS2 (SMR 2·1, 95% CI 1·9,2·4). Cancer incidence was increased (SIR 1·3, 95% CI 1·2,1·5). When tumours observed during the first year of follow-up were excluded, only the cancer risk among APS1 patients remained increased. Cause-specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. Conclusions, Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency. [source] Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal tumoursCLINICAL ENDOCRINOLOGY, Issue 6 2008Nicole Unger Summary Background, Somatostatin mediates its action through five receptor subtypes (sst1,5) that are widely distributed in various endocrine tissues and tumours. Because of the inhibitory effects of somatostatin, long-acting analogues have been synthesized. In contrast to their well-established use in neuroendocrine and pituitary tumours, little is known about their potential use in adrenal tumours. Objective, We examined somatostatin receptor protein expression in adrenal tumours of various aetiologies. Immunostaining was performed with specific polyclonal antibodies for sst1,5. Design, Seven benign and eight malignant pheochromocytomas (PHEOs), eight aldosterone-secreting adenomas (APAs), nine cortisol-secreting adenomas (CPAs), seven nonfunctioning adrenal tumours (NFAs) and 25 adrenal carcinomas (CAs) as well as eight normal adrenal glands were investigated. Measurements, Staining pattern, distribution and subcellular localization of the somatostatin receptor subtypes were evaluated. Results, In the majority of normal cortices the expression of sst1,5 was limited to the reticular zone. The medulla was predominantly positive for sst3. Most cortical adenomas were positive for all five subtypes. However, in the majority of these tumours, less than 30% of cells were positively stained. A high expression of sst4 was found in CPAs but only very few cortical carcinomas exhibited sst immunostaining. All benign PHEOs were positive for sst3. The majority presented with more than 60% of tumour cells stained. By contrast, only six out of eight malignant PHEOs were positive for sst3. Conclusions, Somatostatin receptor subtypes are expressed in PHEOs as well as in tumours of the adrenal cortex with tumour-specific distribution patterns. This may offer new diagnostic and therapeutic possibilities. [source] Interactions of orexins/hypocretins with adrenocortical functionsACTA PHYSIOLOGICA, Issue 3 2010S. M. Kagerer Abstract The neuropeptides orexin A and B (hypocretin-1 and -2) are involved in numerous central regulation processes such as energy homeostasis, sleeping behaviour and addiction. The expression of orexins and orexin receptors in a variety of tissues outside the brain and the presence of orexin A in the circulation indicate the existence of an additional peripheral orexin system. Furthermore, it is well established that orexins exert an influence on the regulation of the hypothalamus,pituitary,adrenal axis, acting both on its central and peripheral branch. In rat and human adrenal cortices the expression of both orexin receptors has been verified with a predominance of OX2R. The local expression of orexin receptors was observed to be gender specific and to be modified by plasma glucose and insulin concentrations, nutritional status as well as gonadal steroids. Various studies consistently demonstrated orexin A to enhance glucocorticoid secretion of rat and human adrenal cortices, while orexin B was found to be either less potent or ineffective. On the contrary, the influence of orexins on adrenocortical aldosterone production and cell proliferation is still more controversial. Recent findings indicate that orexins stimulate adrenocortical steroidogenesis by augmenting transcription of selective steroidogenic enzymes and proteins such as steroidogenic acute regulatory protein. Both, Gq and Gs, signalling pathways with a downstream activation of MAP kinases appear to be involved in this regulation. [source] ES07 MICROARRAY GENE EXPRESSION ANALYSIS OF HUMAN ADRENOCORTICAL TUMOURSANZ JOURNAL OF SURGERY, Issue 2007P. S. H. Soon Introduction Adrenal tumours are common, occurring in 7% of patients over the age of 50. Adrenocortical carcinomas, however, are rare, with an incidence of two per million population per year. The management of adrenocortical tumours is complex, compounded by the difficulty in discriminating benign from malignant tumours using conventional histology. A molecular marker which could reliably distinguish between the two groups would be valuable in patient management. Objectives The aim of this study was to identify molecular markers which will discriminate between adrenocortical carcinomas and adenomas using microarray gene expression analysis. Methods This study used RNA from 6 normal adrenal cortices, 16 adrenocortical adenomas and 12 carcinomas. Only samples with an RNA integrity number of 7.5 or greater were used. The samples were hybridised to Affymetrix HGU133plus2.0 genechips. Data analysis was performed with Partek and affylmgui softwares. Results Using a cutoff of B > 2 and M > 2 or <,2, 217 genes were found to be significantly differentially expressed between adrenocortical adenomas and carcinomas. Of these genes, 120 were unpregulated while 97 were downregulated. Seven of these genes have been selected for validation studies with real time reverse transcription polymerase chain reaction. Conclusion In this study, we found 217 genes which were significantly differentially expressed between adrenocortical adenomas and carcinomas. With validation and further studies, these genes will provide further insight into the pathogenesis of adrenocortical tumours as well as possibly proving to be reliable discriminators between adrenocortical adenomas and carcinomas. [source] Persistent isolated hypocortisolism following brief treatment with trilostaneAUSTRALIAN VETERINARY JOURNAL, Issue 12 2008IK Ramsey A 12-year-old male neutered Miniature Poodle with confirmed pituitary-dependent hyperadrenocorticism was treated with trilostane. After three doses, it developed clinical and laboratory changes suggestive of isolated hypocortisolism (,atypical hypoadrenocorticism'), which persisted and progressed for more than 3 months despite immediate withdrawal of the trilostane. The clinical signs of hyperadrenocorticism resolved without further trilostane. After 3 months, prednisolone treatment was started and the clinical signs of hypocortisolism resolved. Prednisolone therapy was required for more than 1 year. Ultrasonography initially demonstrated large hypoechoic adrenal cortices, typical of dogs with hyperadrenocorticism, which then became small and heteroechoic, consistent with the development of adrenal necrosis. Persistent isolated hypocortisolism has not been reported previously as a complication of trilostane therapy. The case is also remarkable for the very short duration of trilostane therapy that elicited this complication. Clinicians should be aware that trilostane therapy may result in adrenal necrosis, even in the very earliest stages of therapy, but prompt action can prevent a life-threatening situation. [source] | ||||||||||||||||