Observations on the fine structure of propylthiouracil‐induced “brown degeneration” in the zona reticularis of mouse adrenal cortex
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Abstract Propylthiouracil (6‐propyl‐2‐thiouracil), an anti‐thyroid agent, was fed to mice in a concentration equal to 0.1% of their diet for periods of 10 and 15 weeks. The cells of the inner zone of the adrenal cortex were examined with the electron microscope. In animals receiving propylthiouracil for ten weeks mitochondria were altered and the smooth endoplasmic reticulum (SER) showed a marked focal proliferation. In contrast to control animals rough endoplasmic reticulum was abundant and was frequently associated with the hyperplastic SER. After 15 weeks these alterations were no longer present but had been replaced by a spectrum of “brown degeneration.” The less affected cells were characterized by increased numbers of liposomes and lysosomes and the more affected cells by liposomal and mitochondrial degeneration. These observations emphasize that “brown degeneration” is a true degenerative process and not a spontaneous proliferation of ceroid pigment. It is suggested that the changes described may be directly related to an alteration in cholesterol metabolism.Keywords:
Propylthiouracil
Degeneration (medical)
Zona reticularis
Reticulum
Zona fasciculata
In dogs receiving oral treatment with 2,2-bis (2-chlorophenyl-4-chlorophenyl)- l,l-dichloroethane (o,p' DDD) for periods of 2, 4, and 6 days, the secretion rate of 17-hydroxycorticosteroids was markedly decreased. Histological observations on the adrenal cortex showed that focal degenerative lesions developed first in the zona reticularis, then in the zona fasciculata. No changes were seen in the zona glomerulosa even after 6 days treatment. Morphological changes in the zona reticularis and zona fasciculata were slight after 2 days treatment although there was alreacty a marked reduction in the digitoninprecipitable compounds of these zones. After 6 days treatment, 3β-hydroxy sterols were almost absent from the zona fasciculata and zona reticularis. Distribution of sudanophilic lipids of these zones remained unaltered during this period.
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Zona reticularis
Zona
Steroid 11-beta-hydroxylase
Histology
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Adrenarche is considered to occur as a result of intra‐adrenal changes in steroidogenic enzymes involved in C 19 steroid production. The present study was conducted because developmental changes in steroidogenic enzymes have not been examined well in human postnatal adrenal. Twenty‐four specimens of nonpathological human adrenals from 7 months to 62 years retrieved from autopsy files. Immunohistochemistry for P450 side‐chain cleavage (P450scc), 17α hydroxylase (P450c17), dehydroepiandrosterone sulfotransferase (DHEA‐ST), P450 oxidoreductase, cytochrome b5, and 3β‐hydroxysteroid dehydrogenase (3βHSD) was per‐formed in these specimens, and the immuno‐intensity was evaluated using CAS 200 computed image analysis system. Immunoreactivity of P450scc was marked in the zona glomerulosa, fasciculata and reticularis in the adrenal glands of all the cases examined. P450c17 and DHEA‐ST immunoreactivity was weak in the zona fasciculata and reticularis in the adrenals of age 7 months to 5 years, but thereafter became prominent in the zona reticularis. Immunoreactivity of P450 oxidoreductase and cytochrome b5, components of the electron transfer system hypothesized to regulate the 17–20 lyase activity of P450c17, was weak in all three zones of adrenal cortex from 7 months to 5 years, and became more marked in the zona reticularis after age 5 years. 3βHSD immunoreactivity was marked in all three zones of the adrenal cortex from 7 months to 8 years but thereafter decreased in the zona reticularis. These data suggest that the human adrenal zona reticularis markedly begins to develop morphologically and functionally at around 5 years of age. The increased level of P450c17, DHEA‐ST, P450 oxidoreductase, and cytochrome b5, and the decreased level of 3βHSD in the reticularis is likely to contribute to increased C 19 steroid production during adrenarche.
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Steroid 11-beta-hydroxylase
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Corticosterone
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To examine the regulation of the zona fasciculata and the zona reticularis of the guinea pig adrenal cortex, animals were placed on a chronic regimen of dexamethasone. Changes in adrenal zonal weight, cholesterol side-chain cleavage activity, and tissue and serum steroid concentrations were measured after 1 month of dexamethasone administration. With dexamethasone treatment, the weight of the outer zone (glomerulosa/fasciculata) decreased significantly, while the weight of the inner zone (reticularis) did not change. Cholesterol sidechain cleavage activity in mitochondria isolated from the outer zone also declined significantly, while a similar activity in the inner zone did not change. The serum cortisol concentration in response to dexamethasone administration decreased by 85%, as did the concentrations of cortisol and progesterone in the outer zone; the concentration of cortisol in the inner zone decreased by only one third, while the concentration of progesterone did not change. These results in association with previous reports indicate that the zona reticularis of the guinea pig adrenal cortex (in contrast to the zona fasciculata) is not regulated by ACTH in terms of either steroidogenesis or maintenance of cell growth. (Endocrinology115: 1838–1841,1984).
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The content of fatty substances was examined: neutral fats, triglycerides and phospholipids, in the adrenal gland cortex after exposing white rats to the influence of detergents in the duration of one month. Neutral fats conduct themselves in the following manner: their quantity is decreased in the cells of zona glomerulosa and is increased in the zona fasciculata and zona reticularis. As far as the presence of triglycerides in the adrenal cortex is concerned, it is typical that they are increased quantity-wise in all three zones of the adrenal gland cortex. Phospholipids in their presence, give the following appearance: this group of fatty substances is of increased content in the cells of zona glomerulosa; a slight increase of these substances is typical for zona fasciculata while their increase is evident in the cells of zona reticularis. All of the described features, regardless of the group of fatty substances, indicate the stimulated activity of the adrenal gland cortex after the application of histochemical methods.
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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 (CCl 4 ) causes adrenocortical necrosis, but only of the innermost zone of the gland, the zona reticularis. The apparent reason for the localized effect of CCl 4 in the adrenal cortex is that only the cells of the zona reticularis have the enzymatic capacity to activate CCl 4 , 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.
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The study aimed to find out the effect of sulfonamide combined with Trimetaprim-Biseptol 480 on the adrenal cortex in post-operative shock after removal of SPIGELian lobe (lobectomy of the lobus caudatus and unilaterally of one kidney with its suprarenal gland. The study was performed on a material of white rats which were post-operatively administered Biseptol 480 in doses 5 times bigger than those given to men. It was attempted to determine histochemically the intensity of the adrenal cortex' function by testing the number of lipid droplets, activity of the main enzyme of steroidogenesis (beta-hydroxy steroid dehydrogenase) and the level of alpha-ketols (as the final stage of steroidogenesis). Pathomorphologic examinations were also performe. On the basis of the present study's results, it was observed that - in the case of liver-lobectomy - the zona fasciculata and zona reticularis are functionally stimulated but the zona glomerulosa becomes insufficient. In the case of nephrectomy plus suprarenal gland's removal, all the adrenal cortex becomes insufficient. Administration of Biseptol in the 1st case contributed to hormonal inactivation of the zone glomerulosa cells, but in the 2nd case, it caused an increased activity of steroid dehydrogenase and an increase of the alpha-ketol level in the zona fasciculata.
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Morphological and histochemical study on the adrenal cortex of the dexamethasone-treated albino rat.
Morphological and histochemical examinations of the changes induced in the adrenal cortex by the administration of Dexamethasone (Decadron phosphate) to rats for 14 consecutive days were made at intervals during a 28-day post-treatment period, in order to follow the histo-functional recovery of this gland from the changes induced. The modifications that had occurred by the end of the treatment consisted of a decrease in the width of the zona fasciculata and the zona reticularis, an increase in the lipidic content, and degenerative mitochondrial signs in the zona glomerularis. Seven days after discontinuing treatment, we observed the disappearance of the zona intermedia, which reappeared on the 14th day after treatment. From this day on, the adrenal gland tended progressively to complete recovery. Dexamethasone therefore produces both short-term and long-term morphological and histochemical changes in all the adrenocortical zonae.
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Steroid 11-beta-hydroxylase
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Zona reticularis
Steroid 11-beta-hydroxylase
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