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[Glucocorticoid and androgenic functions of the adrenal cortex and the state of the sympathetic-adrenal system in thyrotoxicosis with primary organic disease of the central nervous system].

In patients with thyrotoxicosis combined with primary affection of the central nervous system (CNS)-encephalitis, diencephalitis-there was revealed, like in common thyrotoxicosis, an increased production by the adrenal cortex of hydrocortisone, its intensified transformation and inactivation, reduced production of 17-ketosteroid chiefly due to the fall of dehydroepiandrosterone content, an increased urinary excretion of adrenaline and a decreased-of noradrenaline. The use of functional test with the ACTH administration demonstrated organic affection of the CNS to sharply aggravate the weakening and even the exhaustion of the functional reserves of the glomerular and the reticular zones of the adrenal cortex developing during thyrotoxicosis, and also the reserve possibilities of the sympathico-adrenal system. Direction of the changes in the 24-hour excretion of 17-OCS and corticosteriods was the same in the majority of cases. The latter can point to the presence of functional association between the hypothalamus-hypophysis-adrenal cortex systems and adrenergic regulation in these patients.

17-Hydroxycorticosteroids↗

Effects of long term stimulation of ACTH and angiotensin II-secretions on the rat adrenal cortex.

In the rat adrenal cortex, aldosterone synthase cytochrome P450 (P450aldo), a mineralocorticoid synthesizing enzyme, localizes in the zona glomerulosa (zG), while cytochrome P45011 beta (P45011 beta), a glucocorticoid synthesizing enzyme, localizes in the zonae fasciculata-reticularis (zFR). In between zG and zF, a cell-layer which contains neither P450aldo nor P45011 beta is present, where replicating cells were abundant as judged by the incorporation of bromodeoxyuridine (BrdU) and/or by detecting PCNA in their nuclei. When plasma ACTH level of the rat was raised 3-fold for 2-3 weeks by the administration of metyrapone, a potent inhibitor of glucocorticoid formation, most of zG cells containing P450aldo disappeared, while zF cells with P45011 beta increased. Under the conditions, the cell-layer without P450aldo and P45011 beta became very thin, and replicating cells were mainly in the outermost portion of zF. When angiotensin II secretion was also stimulated for 2-3 weeks by feeding the rats on Na-deficient diet, the P450aldo-containing cells proliferated to form a thicker zG (7-8 cells-thick from 1-2), while the width of zF containing P45011 beta decreased slightly. Coincidently the cell-layer devoid of P450aldo and P45011 beta became thin, though slightly, and numbers of replicating cells significantly increased in and around the inner edge of the proliferated zG. When both ACTH and angiotensin II secretions were stimulated simultaneously, the cell-layer without P450aldo and P45011 beta almost disappeared and replicating cells were around the boundary of zG and zF. Based on these results we propose that the cell-layer between zG and zF devoid of P450aldo and P45011 beta is the stem cell layer of rat adrenal cortex.

Adrenal Cortex↗

[Morphological manifestations of acute stress reactions in the adrenal cortex of hypokinetic rats].

Adrenal changes in response to an acute stress-effect (5 h-immobilization stress) were investigated in female rats exposed to hypokinesia for 3 months. The rate of delipoidization in the adrenal cortex increased in the rats exposed to an acute stress after short-term (1-2 weeks) hypokinesia. The process of delipoidization did not advance in the rats exposed to an acute stress in the course of prolonged (2-3 months) hypokinesia. This does not yet prove the lack of the stress reaction but gives evidence that during prolonged hypokinesia the adrenals develop the capacity to react to an additional effect without the entire complex of morphological signs typical of an acute stress reaction. The immobilization test used to assess the state of the adrenal cortex has shown that it does not deteriorate even during 3-month hypokinesia (in this study).

Acute Disease↗

Functional differences between the outer and inner zones of the guinea pig adrenal cortex.

The guinea pig adrenal cortex is grossly composed of two regions: an outer, yellow zone and an inner, brown zone. These zones, which represent 33% and 66% of the total adrenocortical volume, respectively, can be separated by blunt dissection. It has been previously reported that specific pregnenolone and pregnenolone sulfate binding proteins are present in the high speed supernatant fraction (cytosol) prepared from the whole adrenal cortex of the guinea pig. However, when cytosol was prepared from the separate outer and inner cortical zones, it was found that the steroid-binding proteins were concentrated in the inner zone. This correlated with the level of pregnenolone which was significantly greater in the cytosol of the inner zone where greater than 50% was found to be bound. In contrast, the concentration of cortisol was 30 times greater in the cytosol of the outer cortical zone and less than 4% was found to be bound. These data suggest that cortisol is produced primarily in the outer cortical zone, a region which comprises only one-third of the total cortical volume. On the other hand, the coexistence of pregnenolone and its binding protein in the inner cortical zone, a region which comprises two-thirds or the greatest cortical volume, indicates a different functional status for this zone. The exact hormonal control of these two vastly different regions (chromatically, morphologically, and functionally) remains to be determined. It is speculated that the inner cortical zone of the adult guinea pig adrenal is the counterpart of the fetal cortex which did not involute.

Adrenal Cortex↗

Calcium-dependent protein kinase activity and protein phosphorylation in zones of the adrenal cortex.

The guinea pig adrenal cortex is composed of two chromatically distinct concentric zones. The steroidogenic response to ACTH by the two zones is likewise distinct: ACTH stimulates cholesterol side-chain cleavage activity in the outermost zone, but fails to do so in the inner zone. This despite the fact that adenylate cyclase activation by ACTH and cAMP formation are similar for the two zones. To further examine this model, protein kinase activity and protein phosphorylation have been examined. It was found that the cAMP-dependent, Ca2+/phospholipid-dependent, and Ca2+/calmodulin-dependent protein kinase activities were significantly higher in the outer zone than in the inner zone by 70, 60 and 800%, respectively. Although the physiological meaning of a zonal difference in protein kinase activity is not as yet clear, the marked difference in Ca2+/calmodulin-dependent protein kinase activity between the inner and outer zones correlates well with the marked difference in steroidogenesis that exists between the two zones. Of the Ca2+/calmodulin-dependent protein kinases known to exist, there is preliminary evidence to suggest the presence of kinase III in the guinea pig adrenal cortex. Protein phosphorylation induced by the three kinase systems in the two adrenocortical zones revealed notable differences in phosphoprotein patterns. In addition, it was found that exogenous calmodulin was phosphorylated and that the kinase responsible for this was more active in the inner zone.

Adrenal Cortex↗

Cytochemical localization of calcium in mitochondria of regenerating rat adrenal cortex. A study of adrenal regeneration hypertension.

The distribution of calcium in the mitochondria of the adrenal gland was studied during development of adrenal regeneration hypertension. Electron opaque precipitate (calcium antimonate) was localized predominantly in the intercristal space within mitochondria and in cisternae of smooth endoplasmic reticulum. Stereological techniques were employed to quantitate the volume per cell of precipitate. Compared to the zona glomerulosa or zona fasciculata of controls, the volume per cell of electron opaque precipitate in mitochondria of the regenerating gland was significantly reduced at 5 and 14 days after enucleation. By 21 days, the volume of mitochondrial precipitate per cell, while more than that in zona glomerulosa cells, was less than in mitochondria from control zona fasciculata cells. As a comparison, normal rats were treated with ACTH or were hypophysectomized. ACTH-treatment did not greatly increase the precipitate associated with mitochondria in the zona fasciculata. Mitochondria in the zona fasciculata of hypophysectomized rats however showed a significant reduction in precipitate per cell correlating with a significantly reduced volume of mitochondria per cell as compared to those of control zona fasciculata cells. Giant mitochondria were observed in hypophysectomized animals. Volume of precipitate per cell associated with smooth endoplasmic reticulum was increased slightly, but significantly, as compared to that in controls treated with ACTH, whereas in hypophysectomized rats, it was decreased significantly. Adrenocortical cells arising from the zona glomerulosa and sub zona glomerulosa region differentiate to zona fasciculata cells during regeneration and may have an altered capacity to concentrate calcium. Change in intramitochondrial calcium may be correlated with the reduced formation of corticosterone from its precursor, deoxycorticosterone, thereby contributing to the pathogenesis of adrenal regeneration hypertension.

Adrenal Cortex↗

Coregulatory protein-orphan nuclear receptor interactions in the human adrenal cortex.

The capacity of the adrenal to produce steroids is controlled in part through the transcriptional regulation of steroid enzymes. The orphan nuclear receptor steroidogenic factor 1 (SF-1) is central to the transcriptional regulation of all steroid hydroxylase enzymes, whereas nur77 can preferentially regulate steroid enzyme genes relevant to cortisol production. We hypothesised that, in the presence of secretagogues, SF-1 and nur77 may differentially interact with coregulatory proteins in the human adrenal cortex. Both coregulatory proteins, steroid receptor coactivator (SRC-1) and silencing mediator for retinoid and thyroid hormones (SMRT), were found to be expressed in the zona fasciculata and reticularis in the human adrenal cortex, but were largely absent from the zona glomerulosa. Both coregulatory proteins were colocalised with SF-1 and nur77. In the H295R adrenal tumour cell line, SF-1 and nur77 transcripts were increased in cells in the presence of forskolin, whereas nur77 mRNA was also induced with angiotensin II (AII). The coactivator SRC-1 mRNA was increased in the presence of both forskolin and AII. Forskolin induced recruitment of SRC-1 to the SF-1 response element and induced SRC-1-SF-1 interactions, whereas AII increased recruitment of SRC-1 to the nur77 response element and induced SRC-1-nur77 interactions. The corepressor SMRT interacted with SF-1 in the presence of AII and with nur77 in cells treated with forskolin. Orphan nuclear receptor-coregulatory protein interactions may have consequences for the regulation of key steroidogenic enzymes in the human adrenal cortex.

Adrenal Cortex↗

[Demonstration by spectroscopy NMR at 1,5 Tesla of changes in lipid/water ratio in pathology of the adrenal cortex].

By NMR proton spectrometry with a main field of approximately 1.5 Tesla the authors have studied on pieces obtained at surgery changes of the lipid/water ratio in the cortex of diseased adrenal glands. On the basis of 58 samples taken from 20 different glands they show that this ratio is comparable in hyperplasias and adenomas but quite significantly reduced in carcinomas. They are therefore of the opinion that this ratio might serve as a malignancy index in spectroscopic imaging of patients bearing tumors of the adrenal cortex.

Adenoma↗

[Ultrastructure of the zone fascicularis of the adrenal cortex of the rat after a single physical loading to fatigue and in the recovery period].

Ultrastructure of the fascicular zone in the cortex of the adrenals has been studied in untrained rats after a single physical loading (swimming with an additional load up to fatigue) and during restorative period (24, 48, 72 and 96 h of rest after the loading). The massive release of hormones during the prolonged physical work, as well as during the 1st and the 3d days of rest are estimated by ultrastructural changes in adrenocorticocytes. Signs of an increased permiability of the histohematic barrier in the gland are mostly manifested in 48 h after the loading: in the wall of the smallest vessels ruptures and discharge of formed elements of blood into the pericapillary space; numerous macrophages in the intercellular space phagocytaze the products of degeneration; residual bodies, fragments of decaying cells are seen in the blood capillary lumen. In 96 h of rest, in the fascicular zone of the adrenal cortex changes directed to restoration of the cholesterin depot are observed.

Adrenal Cortex↗

Rat adrenal cortex is a source of a circulating ouabainlike compound.

To determine if the adrenal gland may be the source of plasma-borne ouabainlike compound (OLC) in rats, we 1) measured immunoreactivity expressed as OLC equivalents in extracts from a wide variety of central and peripheral tissues and, for adrenal cortex and medulla, chromatographed the extracts to determine to what extent immunoreactivity in the adrenal was OLC, and 2) measured OLC in the plasma of adrenalectomized and adrenal demedullectomized rats. The highest levels of immunoreactivity were found in adrenal cortex, adrenal medulla, atria, and the pituitary. Based on high-performance liquid chromatographic retention time, immunoreactivity in the adrenal cortex was almost exclusively immunoreactive OLC. Removal of this rich source of OLC from rats resulted in an approximate 50% decrease in circulating levels of OLC by 6 days after removal. Furthermore, although adrenal demedullectomy also caused a decrease in OLC 3 days after surgery, the decline was sustained only with total adrenalectomy, in that plasma levels of OLC in demedullectomized rats 6 days after surgery had returned to levels equal to those of sham controls. Taken together, these findings strongly suggest that the adrenal cortex is a major contributor to circulating OLC in the rat.

Adrenal Cortex↗