scholarly journals Adrenal Gland Toxicity: Chemically Induced Dysfunction

1988 ◽  
Vol 7 (1) ◽  
pp. 45-69 ◽  
Author(s):  
H. D. Colby

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.

2003 ◽  
Vol 178 (3) ◽  
pp. 479-489 ◽  
Author(s):  
T Vanttinen ◽  
J Liu ◽  
T Kuulasmaa ◽  
P Kivinen ◽  
R Voutilainen

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.


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

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.


1972 ◽  
Vol 20 (3) ◽  
pp. 173-179 ◽  
Author(s):  
MARGARET E. BEARD

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.


1968 ◽  
Vol 41 (3) ◽  
pp. 319-326 ◽  
Author(s):  
E. H. D. CAMERON ◽  
M. A. BEYNON ◽  
K. GRIFFITHS

SUMMARY The ability of cells from the zona fasciculata and the zona reticularis of the human adrenal cortex to transform labelled pregnenolone and progesterone to cortisol in vitro was investigated. Examination of the 3H:14C ratios of 16α-hydroxyprogesterone, 17α-hydroxyprogesterone, 11-deoxycorticosterone and cortisol formed during incubations in vitro suggested that the role of progesterone in the transformation of pregnenolone to cortisol might be a relatively minor one. An attempt was subsequently made to estimate the relative importance of the biosynthetic pathway to cortisol by way of progesterone in hyperplastic adrenal tissue by a mathematical approach.


2005 ◽  
Vol 184 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Weiye Wang ◽  
Lishan Wang ◽  
Akira Endoh ◽  
Geoffrey Hummelke ◽  
Christina L Hawks ◽  
...  

In order to establish whether there are differences in DNA-binding proteins between zona fasciculata (ZF) and zona reticularis (ZR) cells of the human adrenal cortex, we prepared nuclear extracts from separated ZF and ZR cells. The formation of DNA–protein complexes was studied using an element in the first intron of the type I and type II 3β-hydroxysteroid dehydrogenase genes (HSD3B1 and HSD3B2). Using the element in the HSD3B2 gene as a probe, a complex (C1) was formed with extracts from ZF cells but was formed only at a low level with ZR cell extracts. Another pair of complexes (C2/C3) was formed with both ZF and ZR cell extracts. The ZF-specific protein forming C1 was enriched by column chromatography on DEAE-Sepharose and carboxymethyl-Sepharose. Oligonucleotide competition analysis on the enriched fraction gave results consistent with those obtained on the unfractionated material. A further enrichment was brought about by passing the protein over an oligonucleotide affinity column based on the HSD3B2 element. The protein bound to the column was identified as α-enolase by mass spectrometry. Although α-enolase is a glycolytic enzyme, it binds to specific DNA sequences and has been found to be present in nuclei of various cell types. We performed immunohistochemistry on sections of adult human adrenal cortex and found α-enolase to be located in nuclei of ZF cells but to be predominantly cytoplasmic in ZR cells. Transfection of an α-enolase expression vector into NCI-H295R human adrenocortical cells increased HSD3B2 promoter activity, suggesting a possible functional role for this protein in regulation of HSD3B2 expression.


1988 ◽  
Vol 119 (2) ◽  
pp. 191-NP ◽  
Author(s):  
K. Shinzawa ◽  
S. Ishibashi ◽  
M. Murakoshi ◽  
K. Watanabe ◽  
S. Kominami ◽  
...  

ABSTRACT In an attempt to elucidate the functional role of the three zones of the adrenal cortex, the localization of microsomal cytochrome P-450s (P-45017α,lyase and P-450C21) and their relation to steroidogenesis in the guinea-pig adrenal cortex were studied. The intracellular localization and zonal distribution of P-45017α,lyase and P-450C21 were examined by the direct peroxidase-labelled antibody technique. The cytochromes were localized immunocytochemically on the smooth-surfaced endoplasmic reticulum. P-45017α,lyase was found to be distributed in the zona fasciculata, especially in the externa, and less in the zona reticularis. The zona glomerulosa was negative for immunohistochemical staining for P-45017α,lyase. In contrast, P-450C21 was distributed in all three zones in the adrenal cortex. The cytochrome P-450 contents and their steroidogenic activities were determined with microsomes prepared from the outer zone (zonae glomerulosa and fasciculata) and from the inner zone (zona reticularis) of guinea-pig adrenals. Using an enzyme-linked immunosorbent assay, the ratio of P-450C21 content in the inner zone to that in the outer zone microsomes was estimated to be 1 ·24. 21-Hydroxylase activity was higher in the inner zone microsomes, which was in good agreement with the relative P-450C21 contents. The ratio of P-45017α,lyase content in the inner zone to that in the outer zone microsomes was estimated to be 0·75. 17α-Hydroxylase and C17–20-lyase activities were five- to sixfold greater in the outer than in the inner zone microsomes, which could not be explained by the P-45017α,lyase contents in the two zones. The effects of ACTH on the zonal distribution of microsomal cytochrome P-450s and their steroidogenic activities were also investigated. J. Endocr. (1988) 119, 191–200


2020 ◽  
Vol 48 ◽  
Author(s):  
Leonardo Oliveira Trivilin ◽  
Francisco De Assis Pessoa Júnior ◽  
Maria Aparecida Da Silva ◽  
Leandro André Milholli ◽  
Felipe Martins Pastor ◽  
...  

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.


2015 ◽  
Vol 9 (2) ◽  
pp. 89-93
Author(s):  
Dilruba Siddiqua ◽  
Abu Sadat Mohammad Nurunnabi ◽  
Fatema Johora ◽  
Hasna Hena ◽  
Sunjida Shahriah ◽  
...  

Background: The human adrenal cortex shows a distinct proportion of three zones, named zona glomerulosa, zona fasciculate & zona reticularis, from outer inwards, in its histological appearance with differences in its cellular components and functions. Objective: The aim of the present study was to see the variation in the proportion of zones of the adrenal cortex in different age-group in a Bangladeshi population. Methods: This cross-sectional, descriptive study was done in the Department of Anatomy, Dhaka Medical College, Dhaka, from July 2008 to June 2009, based on collection of 140 post mortem human adrenal glands from 70 unclaimed dead bodies which were in the morgue under examination in the Department of Forensic Medicine, Dhaka Medical College, Dhaka. The samples were divided into four age-groups including A (11-20 years), B (21-30 years), C (31-40 years) & D (41-60 years). Histological slides were prepared by using routine haematoxylin and eosin stain (H & E). Five best prepared slides from each group were examined under light compound microscope with low magnification. The thickness of different layers adrenal cortex were measured by using ocular and stage micrometer and then converted into percentage volume. Results: The mean volume of the zona glomerulosa, zona fasciculata and zona reticularis of the right adrenal cortex were found 14.16±0.79%, 78.40±1.14%, 7.44±0.52% in group A; 14.58±0.38%, 78.00±0.71%, 7.42±0.38% in group B; 14.34±0.83%, 78.56±0.52%, 7.30±0.50% in group C; 14.08±1.23%, 78.80±1.10%, 7.10±0.22% in group D respectively. The mean volume of the zona glomerulosa, zona fasciculata and zona reticularis of the left adrenal cortex were found 14.66±0.34%, 78.84±0.82%, 7.72±0.48% in group A; 14.62±0.30%, 78.54±0.84%, 7.58±0.43% in group B; 14.90±0.96%, 79.20±0.45%, 7.34±0.42% in group C; 14.70±1.25%, 79.40±0.55%, 7.30±0.35% in group D respectively. Conclusion: No difference was found statistically significant in the percentage volume of the three zones of the adrenal cortex with advancing age in Bangladeshi people. DOI: http://dx.doi.org/10.3329/jbsp.v9i2.22803 Bangladesh Soc Physiol. 2014, December; 9(2): 89-93


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