scholarly journals Expression of activin/inhibin signaling components in the human adrenal gland and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis

2003 ◽  
Vol 178 (3) ◽  
pp. 479-489 ◽  
Author(s):  
T Vanttinen ◽  
J Liu ◽  
T Kuulasmaa ◽  
P Kivinen ◽  
R Voutilainen
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Apoptotic Cell ◽  
Regulatory Protein ◽  
Physiological Role ◽  
Activin A ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Zona Fasciculata ◽  
Zona Reticularis ◽  
Signaling Components

Activins and inhibins are structurally related glycoprotein hormones modulating pituitary FSH secretion and gonadal steroidogenesis. Activins and inhibins are also produced in the adrenal cortex where their physiological role is poorly known. Hormonally active human adrenocortical tumors express and secrete inhibins, while in mice adrenal inhibins may function as tumor suppressors. To clarify the significance of adrenal activins and inhibins we investigated the localization of activin/inhibin signaling components in the adrenal gland, and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis.Activin receptor type II/IIB and IB, activin signal transduction proteins Smad2/3, and inhibin receptor betaglycan were expressed throughout the adrenal cortex, whereas Smad4 expression was seen mainly in the zona reticularis and the innermost zona fasciculata as evaluated by immunohistochemistry. Treatment of cultured adrenocortical carcinoma NCI-H295R cells with activin A inhibited steroidogenic acute regulatory protein and 17alpha-hydroxylase/17,20-lyase mRNA accumulation as evaluated by the Northern blot technique, and decreased cortisol, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate secretion as determined by specific enzyme immunoassays. Activin A increased apoptosis as measured by a terminal deoxynucleotidyl transferase in situ apoptosis detection method. Inhibins had no effect on steroidogenesis or apoptosis.In summary, activin/inhibin signaling components are coexpressed in the zona reticularis and the innermost zona fasciculata indicating full signaling potential for adrenal activins and inhibins in these layers. Activin inhibits steroidogenic enzyme gene expression and steroid secretion, and increases apoptosis in human adrenocortical cells. Thus, the activin-inhibin system may have a significant role in the regulation of glucocorticoid and androgen production and apoptotic cell death in the human adrenal cortex.

scholarly journals Adrenal Gland Toxicity: Chemically Induced Dysfunction

1988 ◽  
Vol 7 (1) ◽  
pp. 45-69 ◽  
Author(s):  
H. D. Colby
Keyword(s):  
Adrenal Cortex ◽  
Covalent Binding ◽  
Critical Role ◽  
Physiological Role ◽  
Metabolic Activation ◽  
Zona Fasciculata ◽  
Zona Reticularis ◽  
Hormone Synthesis ◽  
Chemically Induced ◽  
Endocrine Organs

Among the endocrine organs, the adrenal cortex appears to be the most vulnerable to chemically induced injury. A wide variety of chemicals has been found to cause morphological or functional lesions in the gland. Some of the lesions are highly localized to specific anatomical zones of the adrenal cortex, and the resulting functional deficits depend on the physiological role(s) of the zone affected. In addition, metabolic activation is an important factor contributing to the gland's vulnerability to chemical injury. For example, carbon tetrachloride (CCl4) causes adrenocortical necrosis, but only of the innermost zone of the gland, the zona reticularis. The apparent reason for the localized effect of CCl4 in the adrenal cortex is that only the cells of the zona reticularis have the enzymatic capacity to activate CCl4, resulting in lipid peroxidation and covalent binding to cellular macromolecules. By contrast, the mineralocorticoid antagonist, spironolactone, causes functional lesions in the adrenal cortex that are limited to the middle zone of the gland, the zona fasciculata. The explanation again involves metabolic activation; only the zona fasciculata converts spironolactone to a highly reactive metabolite that effects the destruction of several enzymes that are required for steroid hormone synthesis. These findings indicate that bioactivation plays a critical role in the mechanism(s) of action of various toxic agents on the adrenal cortex and also may be responsible for the anatomically localized effects of many chemicals.

scholarly journals Biometry of Adrenal Glands of Mixed-Breed Dogs

2020 ◽  
Vol 48 ◽  
Author(s):  
Leonardo Oliveira Trivilin ◽  
Francisco De Assis Pessoa Júnior ◽  
Maria Aparecida Da Silva ◽  
Leandro André Milholli ◽  
Felipe Martins Pastor ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Adrenal Glands ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Zona Reticularis ◽  
Mixed Breed ◽  
Mean Width ◽  
Length Width ◽  
The Right

Background: Differences of the size of the adrenal glands, in healthy dogs or in endocrinopathies, undermine correct diagnosis of endocrine disorders and evaluations of the adrenal cortex in relation to its size and possible correlation with endocrinopathies are rare. The aim of the present study was to perform measurements of the length, width, thickness and weight of the adrenal glands of young, adult and elderly mixed-breed dogs and correlate them with the age, sex and weight of animals. In addition, the areas occupied by the zona glomerulosa, zona fasciculata, and zona reticularis of the adrenal cortex were measured in order to establish a microscopic biometric pattern.Material, Methods & Results: The right and left adrenal glands of 12 young (six females and six males), 12 adults (six females and six males), and 12 elderly (six females and six males), all mongrels, derived from routine and necropsied in the Animal Pathology Sector of the Veterinary Hospital of the Federal University of Espírito Santo (HOVET-UFES) were weighed and the length, width, and thickness were measured. For the microscopic measurement of the adrenal cortex, 10 randomly selected samples were submitted to routine histological processing and the microscope slides were observed under a light microscope at 5× and 10× objectives, photodocumented and measurements were obtained from a random portion of the adrenal cortex and the zones composing the cortex were measured in triplicate with the aid of the computerized image analysis software. The left adrenal showed a greater average length than the right adrenal in young, adult, and elderly dogs. The size of the glands in the young and adult dogs is not influenced by the sex of the animals, but in older dogs the females had a greater mean width than the males. The weight of the animals presented a positive correlation in relation to the length and weight of the right and left adrenal glands in all studied groups. The age did not influence the length and weight variables of the glands. However, some differences in thickness and width were observed in the elderly group compared to those in other groups. For the microscopic measurements in the right adrenal gland, the cortex was 1.53 mm, being 0.21 mm for the glomerular zone (14.6% of the total adrenal cortex), 1.04 mm for the zona fasciculata (66.9%), and 0.29 mm for the zona reticularis (18.5%). In the left adrenal gland, the cortex was 1.83 mm, being 0.23 mm for the glomerular zone (13.2% of the total adrenal cortex), 1.23 mm for the zona fasciculata (63.96%), and 0.37 for the zona reticularis (22.84%).Discussion: Studies on the size of the adrenal gland in dogs using macroscopic biometrics are scarce, and the current study presents results regarding mixed-breed (male and female) dogs of different ages, which presented variation in size and weight, which could also influence the size of the adrenal gland. Thus, it can be observed that a variation of measurements can be found, especially for dogs with no defined breed. These results demonstrate the importance of studies that perform the macroscopic analysis of such glands. It was concluded that there was a clear variation in the size of the adrenal glands in mixed-breed dogs of different ages and both sexes; the left adrenal showed greater lengths and weights than the right gland. The sex of the animals did not influence the size of the glands in young and adult dogs, but in elderly dogs, the females showed a greater mean width than the males. The right and left adrenal cortices are formed at a greater percentage by the zona fasciculata, followed by the zona reticularis and zona glomerulosa.

scholarly journals Localisation of the melanocortin-2-receptor and its accessory proteins in the developing and adult adrenal gland

2011 ◽  
Vol 46 (3) ◽  
pp. 227-232 ◽  
Author(s):  
Rebecca J Gorrigan ◽  
Leonardo Guasti ◽  
Peter King ◽  
Adrian J Clark ◽  
Li F Chan
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Accessory Protein ◽  
Zona Fasciculata ◽  
Accessory Proteins ◽  
Similar Function ◽  
Glucocorticoid Deficiency ◽  
Inactivating Mutations

The melanocortin-2-receptor (MC2R)/MC2R accessory protein (MRAP) complex is critical to the production of glucocorticoids from the adrenal cortex. Inactivating mutations in either MC2R or MRAP result in the clinical condition familial glucocorticoid deficiency. The localisation of MC2R together with MRAP within the adrenal gland has not previously been reported. Furthermore, MRAP2, a paralogue of MRAP, has been shown in vitro to have a similar function to MRAP, facilitating MC2R trafficking and responsiveness to ACTH. Despite similar MC2R accessory functions, in vivo, patients with inactivating mutations of MRAP fail to be rescued by a functioning MRAP2 gene, suggesting differences in adrenal expression, localisation and/or function between the two MRAPs. In this study on the rat adrenal gland, we demonstrate that while MRAP and MC2R are highly expressed in the zona fasciculata, MRAP2 is expressed throughout the adrenal cortex in low quantities. In the developing adrenal gland, both MRAP and MRAP2 are equally well expressed. The MC2R/MRAP2 complex requires much higher concentrations of ACTH to activate compared with the MC2R/MRAP complex. Interestingly, expression of MC2R and MRAP in the undifferentiated zone would support the notion that ACTH may play an important role in adrenal cell differentiation and maintenance.

PROPERTIES OF RAT ADRENAL ZONA RETICULARIS CELLS: PRODUCTION AND STIMULATION OF CERTAIN STEROIDS

1979 ◽  
Vol 83 (3) ◽  
pp. 435-447 ◽  
Author(s):  
J. B. G. BELL ◽  
R. P. GOULD ◽  
P. J. HYATT ◽  
J. F. TAIT ◽  
S. A. S. TAIT
Keyword(s):  
Adrenal Cortex ◽  
Significant Role ◽  
Zona Fasciculata ◽  
Cell Type ◽  
Acth Stimulation ◽  
Specific Stimulus ◽  
Zona Reticularis ◽  
Cell Pool ◽  
Stimulation Of

The outputs of corticosterone, deoxycorticosterone and androstenedione from dispersed, purified rat adrenal zona reticularis and zona fasciculata cells have been measured by radioimmunoassay. Preferential production of deoxycorticosterone by zona reticularis cells was demonstrated by their higher basal deoxycorticosterone: corticosterone ratio when compared with zona fasciculata cells. Adrenocorticotrophin (ACTH) stimulated corticosterone output by all cell pools prepared by unit gravity (1 g) sedimentation, zona fasciculata cells being stimulated 130-fold compared with 20-fold for the zona reticularis cells in relation to their basal corticosterone output. In every cell pool, ACTH stimulated the output of corticosterone more than it stimulated the output of deoxycorticosterone. In parallel cell preparations, it was shown that ACTH increased the conversion of tracer amounts of radioactive deoxycorticosterone to corticosterone and decreased the conversion of radioactive corticosterone to 11-dehydrocorticosterone. Adrenocorticotrophin did not increase the conversion of radioactive deoxycorticosterone to total 11-oxygenated steroids (corticosterone+ 11-dehydrocorticosterone). It is unlikely therefore that ACTH stimulates 11 β-hydroxylation. Data indicate that the ratio of deoxycorticosterone to total 11-oxygenated steroids (corticosterone +11-dehydrocorticosterone) is characteristic for each cell type, and that this ratio will be relatively independent of ACTH stimulation or the amount of pregnenolone substrate available. Basal androstenedione outputs were similar for both types of cell, and ACTH stimulation was very small, being slightly greater for zona fasciculata than for zona reticularis cells. The contribution of the zona reticularis cells to the basal output of any steroid by the cells of the inner two zones of the adrenal cortex of the rat was relatively small (20% for deoxycorticosterone and 10% for corticosterone) and was even less after stimulation by ACTH. Unless a specific stimulus can be found, therefore, a significant role for the zona reticularis cannot yet be established.

scholarly journals IDENTIFICATION OF PEROXISOMES IN THE RAT ADRENAL CORTEX

1972 ◽  
Vol 20 (3) ◽  
pp. 173-179 ◽  
Author(s):  
MARGARET E. BEARD
Keyword(s):  
Acid Phosphatase ◽  
Adrenal Cortex ◽  
Zona Fasciculata ◽  
Positive Staining ◽  
Staining Reaction ◽  
Dense Matrix ◽  
Zona Reticularis ◽  
Liver And Kidney ◽  
Branched Structures ◽  
Electron Dense Matrix

Organelles with the ultrastructure and cytochemical characteristics of peroxisomes (microbodies) have been identified in cells of the zona fasciculata and zona reticularis of the rat adrenal cortex. These peroxisomes appear as small, elliptical to spherical or branched structures, enclosed by a single membrane and composed of a moderately electron-dense matrix. They do not possess a nucleoid or core of the type found in peroxisomes of liver and kidney. These organelles show a strongly positive staining reaction with the diaminobenzidine technique for peroxidatic activity of catalase. This staining is inhibited by aminotriazole. In cytochemical preparations revealing acid phosphatase activity, lysosomes are strongly stained and peroxisomes are free of reaction product.

scholarly journals Functional scintigraphy of the adrenal gland

2002 ◽  
Vol 147 (1) ◽  
pp. 13-28 ◽  
Author(s):  
D Rubello ◽  
C Bui ◽  
D Casara ◽  
MD Gross ◽  
LM Fig ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Cell Surface ◽  
Adrenal Cortex ◽  
Cell Surface Receptor ◽  
Cell Surface Receptors ◽  
Zona Fasciculata ◽  
Type I ◽  
Surface Receptors ◽  
Meta Iodo Benzyl Guanidine ◽  
And Storage

Over the last 30 years nuclear medicine imaging of the adrenal gland and its lesions has been achieved by the exploitation of a number of physiological characteristics of this organ. By seeking and utilising features which are quantitatively or qualitatively different from those of the adjacent tissues, functional depiction of the adrenal gland and its diseases, which in most cases retain the basic physiology of their tissue of origin, including both the cortex and the medulla, are now a useful clinical reality. Agents widely used in clinical practice include: (a) uptake and storage of radiolabelled cholesterol analogues via the low density lipoprotein (LDL) receptor and cholesterol ester storage pool in the adrenal cortex ((131)I-6-beta-iodomethyl-norcholesterol, (75)Se-selenomethyl-norcholesterol); (b) catecholamine type I, presynaptic, uptake mechanism and intracellular granule uptake and storage mechanism in the adrenal medulla and extra-adrenal paraganglia ((131)I-, (123)I- and (124)I-meta-iodo-benzyl-guanidine (MIBG), (18)F-metafluoro-benzyl-guanidine); (c) cell surface receptor binding of peptides/neurotransmitters/modulators such as for the family of five subtypes of somatostatin receptors ((123)I-tyr-octreotide, (111)In-DTPA-octreotide, (111)In-DOTA-octreotide and many others); (d) although not specific for the adrenal gland, increased glycolysis by tumours, particularly the most malignant varieties, (18)F-2-fluoro-d-deoxyglucose can thus be expected to depict certain malignant lesions such as malignant pheochromocytomas (particularly the minority which are not detected by MIBG) and adrenal incidentalomas (particularly when they occur in patients with known extra-adrenal malignancies). There are a variety of adrenal tissue characteristics with potential for exploitation but which are not currently in clinical use, and which may, nevertheless, have potential as imaging agents. These include: (a) inhibitors of adrenal cortical steroid hormone synthesis enzymes (e.g. radiolabelled analogues of metyrapone); (b) radiolabelled lipoproteins which bind to adrenocortical LDL receptors; (c) inhibitors of catecholamine biosynthesis enzymes (e.g. radiolabelled analogues of tyrosine and related amino acids); (d) cell surface receptors for various peptides and hormones which may be over-expressed on adrenal cortical or adrenal medullary tumours (e.g. radiolabelled analogues of ACTH on adrenocortical cells of zona fasciculata or zona glomerulosa origin, neurotransmitter/hormone message peptides binding to cell surface receptors such as bombesin, vasoactive intestinal polypeptide, cholecystokinin and opiate peptides); (e) the adrenal cortex can also synthesise cholesterol ab initio from acetate, and preliminary studies with (11)C-acetate positron emission tomography have shown interesting results.

Distinct regional localization of neurocalcin, a Ca2+-binding protein, in the bovine adrenal gland

1993 ◽  
Vol 138 (2) ◽  
pp. 283-NP ◽  
Author(s):  
A. Nakano ◽  
M. Terasawa ◽  
M. Watanabe ◽  
K. Okazaki ◽  
S. Inoue ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Dissociation Constant ◽  
Adrenal Medulla ◽  
Binding Protein ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Physiological Role ◽  
Zona Glomerulosa ◽  
Zona Fasciculata ◽  
Sds Page

ABSTRACT Neurocalcin (molecular weight 23 000 and 24 000) is a Ca2+-binding protein with three putative Ca2+-binding domains and is present in large amounts in nervous tissues. Neurocalcin isoproteins separated by C18 reverse-phase column chromatography are insoluble in buffer solution and it is impossible to determine the dissociation constant of neurocalcin with Ca2+. To overcome this difficulty, recombinant neurocalcin was synthesized, based on one of the cDNAs of the neurocalcin isoproteins. Stoichiometric titration experiments, using recombinant neurocalcin, indicated that this protein bound 2 mol Ca2+/mol protein and that the apparent dissociation constant for Ca2+ was 2·2 μmol/l, suggesting that neurocalcin plays a physiological role in cellular function. Immunoblotting showed that neurocalcin is present in the bovine adrenal gland in addition to the nervous tissues. Neurocalcin, identified by immunoblotting, was purified from the bovine adrenal gland. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of neurocalcin from the bovine brain showed 23 kDa and 24 kDa double bands, while SDS-PAGE of neurocalcin from the adrenal gland showed a single band of apparently 24 kDa, suggesting that the expression of neurocalcin isoproteins differs from tissue to tissue. The content of neurocalcin in the adrenal gland was 10 μg protein/100 g wet tissue. Immunohistochemical analysis showed the occurrence of neurocalcin in zona glomerulosa and adrenal medulla but not in zona fasciculata or zona reticularis. The restricted localization of neurocalcin in the adrenal gland suggests that a similar Ca2+ signal pathway may be present in zona glomerulosa and the adrenal medulla. Journal of Endocrinology (1993) 138, 283–290

STIMULATION OF ADRENAL 5-ENE,3β-HYDROXYSTEROID DEHYDROGENASE BY CORTICOTROPHIN IN VITRO

1978 ◽  
Vol 78 (3) ◽  
pp. 457-458 ◽  
Author(s):  
N. LOVERIDGE ◽  
W. R. ROBERTSON
Keyword(s):  
Adrenal Gland ◽  
Hydroxysteroid Dehydrogenase ◽  
Cellular Biology ◽  
Zona Fasciculata ◽  
Zona Reticularis ◽  
Cytochemical Bioassay ◽  
Low Concentrations ◽  
Kennedy Institute ◽  
Stimulation Of

Division of Cellular Biology, The Mathilda and Terence Kennedy Institute of Rheumatology, Bute Gardens, London, W6 7DW (Received 24 April 1978) It is well established (Chayen, Daly, Loveridge & Bitensky, 1976) that segments of guineapig adrenal gland can be maintained in vitro and will respond to low concentrations (0·005– 5·0 pg/ml) of corticotrophin (ACTH). The response measured in the cytochemical bioassay of ACTH is the loss of ascorbate from the zona reticularis (Chayen, Loveridge & Daly, 1972), which is directly related to secretion of cortisol by these segments (Chayen, Bitensky, Chambers, Loveridge & Daly, 1974). However, because both major zones of the adrenal cortex are involved in steroidogenesis (see, e.g., Symington, 1969; Hyatt, Bell, Gould, Tait & Tait, 1976), the lack of a response in the zona fasciculata seems to be anomalous. To test whether the cells of the zona fasciculata in guinea-pig adrenal segments can respond to low concentrations

VERGLEICHENDE UNTERSUCHUNGEN ZUR BIOGENESE VON STEROIDHORMONEN BEI DURCHSTRÖMUNG ÜBERLEBENDER NEBENNIEREN EINER PATIENTIN MIT CUSHING- UND EINER PATIENTIN MIT CONN-SYNDROM

1963 ◽  
Vol 43 (3) ◽  
pp. 419-429 ◽  
Author(s):  
H. Schriefers ◽  
J. M. Bayer ◽  
M. Pittel
Keyword(s):  
Adrenal Gland ◽  
Adrenal Cortex ◽  
Zona Glomerulosa ◽  
Secretion Rate ◽  
Zona Fasciculata ◽  
Conn’S Syndrome ◽  
Adrenal Cortical Adenoma ◽  
Aldosterone Production ◽  
The Right

ABSTRACT In vitro perfusion experiments were carried out with adrenal glands surgically removed from a patient with Cushing's syndrome (hyperplasia of the adrenal cortex) and a patient with Conn's syndrome (adrenal cortical adenoma). From the perfusates the following steroids were extracted, estimated and identified: cortisol, corticosterone, 11β-hydroxyandrostenedione, cortisone and aldosterone. The secretion capacities of the right Cushing adrenal and of the adrenal gland bearing the adenoma were compared with each other. In both adrenals cortisol was the main secretion product and the secretion rates of aldosterone were lowest and practically equal. The Cushing adrenal differed from the adrenal gland with the adenoma in its higher secretion rate of all investigated steroids except aldosterone, in its higher cortisol/aldosterone ratio and in its response to the administration of ACTH. To this stimulus the aldosterone production of the Cushing adrenal reacted in the same rate as the cortisol release. The adrenal gland with the adenoma of the patient with Conn's syndrome had only a relatively higher aldosterone secretion rate in respect to its lower cortisol production (lower cortisol/aldosterone ratio). The total preparation consisting of the adrenal with the adenoma responded neither to ACTH nor to hypertensin. The missing response of the adrenal cortex not including the tumor to ACTH is explained by the structural change in the sense of the so called regressive transformation (small zona fasciculata with relative large zona glomerulosa and reticularis) which was found in our case. Dehydroepiandrosterone was demonstrable in none of the perfusate extracts even under the condition where the left adrenal of the Cushing patient was perfused with added 17α-hydroxy-pregnenolone.

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