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Perisinusoidal cells in a three-dimensional organization of the adrenal cortex in the monkey.

The adrenal cortex in the macaque monkey was examined under the SEM and TEM to elucidate the surface fine structure of perisinusoidal cells in a three-dimensional organization of the cortex. Parenchymal cells in polyhedral form were arranged in acini in the zona glomerulosa, or in the laminae of closely stacked cells in the zona fasciculata and reticularis. Those acini and laminae were accompanied by sinusoids lined only with an endothelium. Endothelial cells were composed of a protruded perikaryon and a thin layer of peripheral cytoplasm in sieve plates with numerous fenestrations. The perikaryon was sometimes equipped with groups of fenestrated disc-like protrusions. Fine collagen fibrils were distributed in the perisinusoidal space, which was a continuous, slit-like lacune between the endothelial and parenchymal cells. In the perisinusoidal space or intercellular spaces among parenchymal cells were seen two types of perisinusoidal cells: the stellate interstitial cells with several spiny, or attenuated processes entangled with collagen fibrils, and the monstrous wandering cells usually associated with pseudopodia-like processes. The cytoplasm of the interstitial cells showed a structure similar to that of fibroblasts, and contained small numbers of lipid droplets. Intravenously injected chicken blood cells were phagocytized by macrophages on the sinusoidal lining. The fine cytological structure of the macrophages was almost the same as that of the wandering cells. The present findings suggest that the interstitial cells are fibroblastic in nature and belong to the vitamin-A storing cell system, and that the wandering cells are macrophages derived from hematogenous monocytes.

Adrenal Cortex↗

Steroid and xenobiotic effects on the adrenal cortex: mediation by oxidative and other mechanisms.

Because steroids reach high concentrations within the adrenal cortex, effects of the direct interaction of steroids and cytochrome P450 enzymes are possible and may involve oxidative damage. Steroid pseudosubstrate effects studied in cultured adrenocortical cells show that these effects are probably not mediated by steroid receptors. Release of oxidants during pseudosubstrate interaction with cytochrome P450s may be responsible for loss of enzymatic activity observed; enzyme activity can be protected by cytochrome P450 inhibitors, antioxidants, and lowered oxygen concentration. There may be pathological effects of pseudosubstrates in the adrenal cortex. Cytochrome P450/pseudosubstrate effects could be involved in the aging and death of adrenocortical cells in vivo, and necrosis of the adrenal cortex due to excessive ACTH stimulation or due to the action of adrenolytic chemicals could result from damage by oxygen radicals originating from cytochrome P450s. The possible mechanism of damage to the adrenal cortex by the xenobiotics dimethylbenzanthracene, TCDD, 3-methylcholanthrene, and o', p'-DDD are reviewed.

Adrenal Cortex↗

The effect of alpha-melanocyte-stimulating hormone on the adrenal cortex of the fetal rat.

The effect of alpha-melanocyte-stimulating hormone (alpha-MSH) on the fetal adrenal cortex in rat was studied in vivo and in vitro. In vivo, an injection of alpha-MSH stimulated the adrenal cortex slightly. Treatment of the adrenal cortex with alpha-MSH in organ culture caused hyperfunctional change in the innermost layer of the cortex, the detection of which was done by electron microscope. This treatment caused at the same time an increase in corticosterone in the culture medium. Furthermore, comparison was made between alpha-MSH and ACTH with respect to their effect on the fetal adrenal cortex.

Adrenal Cortex↗

Clonality as expression of distinctive cell kinetics patterns in nodular hyperplasias and adenomas of the adrenal cortex.

Although histopathologic criteria for adrenal cortical nodular hyperplasias (ACNHs) and adenomas (ACAs) have been developed, their kinetics and clonality are virtually unknown. We studied 20 ACNHs and 25 ACAs (based on World Health Organization criteria) from 45 females. Representative samples were histologically evaluated, and the methylation pattern of the androgen receptor alleles was analyzed on microdissected samples. Consecutive sections were selected for slide cytometry, flow cytometry, and in situ end labeling (ISEL). Apoptosis was studied by flow cytometry (nuclear area/DNA content plotter analysis) and by ISEL. Appropriate tissue controls were run in every case. Polyclonal gel patterns were revealed in 14/18 informative ACNHs and in 3/22 informative ACAs, whereas monoclonal gel patterns were observed in 4/18 ACNHs and 19/22 ACAs. Overlapping proliferation rates (PRs) were observed in both clonal groups, and apoptosis was detected only in G(0)/G(1) cells, especially in monoclonal ACNHs (3/4; 75%) and in polyclonal ACAs (2/3; 67%). Significantly higher PRs were observed in ACNHs with polyclonal patterns and G(0)/G(1) apoptosis and in ACAs regardless of clonality pattern and presence of G(0)/G(1) apoptosis. All except one ACNH (19/20; 95%) and 15/25 ACAs (60%) showed diploid DNA content, whereas the remaining cases were hyperdiploid. A direct correlation between PR and ISEL was observed in polyclonal lesions (PR = 29.32 ISEL - 1.93), whereas the correlation was inverse for monoclonal lesions (PR = -9.13 ISEL + 21.57). We concluded that only simultaneous down-regulated apoptosis and high proliferation result in selective kinetic advantage, dominant clone expansion, and unbalanced methylation patterns of androgen receptor alleles in ACNHs and ACAs.

Adenoma↗

[Degree and frequency of activation of different adrenal cortex functions in diabetes mellitus patients].

The indices of three adrenal cortex functions were investigated in 517 patients with a moderately severe and severe forms of diabetes mellitus of various duration, outside of the ketoacidosis and hypoglucemia states. Both during decompensation and at the period of unstable compensation (subcompensation) of the disease 3--60% of the patients displayed increased indices of glucocorticoid and mineralocorticoid functions, and 20--38%--of the androgenic ones. Along with different frequency of detection, there was revealed a distinct non-uniformity of different indices elevation. A prevalence of the mineralocorticoid function activation was noted. As suggested, at the mentioned periods of diabetes mellitus functional activity of the adrenal cortex reflected various phases of the oscillatory adaptation process to the frequently repeated stress actions (metabolic disturbances). Possible causes of prevalent aldosterone excretion elevation are discussed.

17-Hydroxycorticosteroids↗

Histopathology of the human adrenal cortex.

The morphological features of the adult human adrenal cortex are described with particular respect to changes induced by alterations in function of the hypothalamo-pituitary axis. The occurrence of nodules in the normal and hyperplastic cortex (Cushing's and Conn's syndromes) is discussed in relation to the diagnostic problems that they still pose. Explanations based on the normal mechanisms of functional zonation in the cortex are provided for the different cell types which comprise cortical neoplasms associated with various syndromes of hypercorticalism (Cushing's, adrenogenital and Conn's syndromes), together with morphological and functional criteria to distinguish adenomas from carcinomas.

Adrenal Cortex↗

Purification and characterization of a substrate protein for mitochondrial ATP-dependent protease in bovine adrenal cortex.

We have purified SP-22, a substrate protein for mitochondrial ATP-dependent protease in bovine adrenal cortex. Native SP-22 showed an M(r) of 350,000 +/- 20,000, and was composed of more than 10 molecules of an M(r) 21,600 subunit. Subcellular and submitochondrial fractionation of adrenocortical tissues revealed that SP-22 was localized in the mitochondrial matrix, suggesting that SP-22 is a natural substrate for ATP-dependent protease, a matrix enzyme. The concentration of SP-22 in adrenocortical mitochondrial fractions was 16 +/- 3 micrograms/mg proteins (mean +/- SD, n = 6) as determined by radioimmunoassay using specific anti-SP-22 antibody. Adrenal cortex showed the highest concentration among the 15 bovine tissues tested, followed by liver, renal cortex, adrenal medulla, heart, and renal medulla. We determined the amino acid sequence of SP-22, which is composed of 195 amino acids. Amino acid 47 was not identified by the sequencer. FAB-mass spectrometry of AA47-AA55 fragment revealed that AA47 was cysteine-sulfinic acid (Cys-SO2H). By a homology search in the NBRF-PIR data base, SP-22 was found to be 91% homologous to murine erythroleukemia cell MER-5 protein, which may have an important role in the induction of differentiation. SP-22 was also homologous to the C22 component of alkyl hydroperoxide reductase in Salmonella typhimurium, thiol-specific antioxidant in Saccharomyces cerevisiae, and some other proteins. Since a segment around AA47 was highly conserved, this residue may be important for the biochemical functions of SP-22.

ATP-Dependent Proteases↗

[The thyroid gland and adrenal cortex in the large fetus and their role in the development of macrosomia].

In a morphological study of thyroid glands and adrenal cortex of large fetuses compared to the controls the authors revealed a significant increase of the thyroid gland functional activity, as well as of glomerular and fascicular zones of adrenal cortex. The functional tension of the thyroid gland appeared to be reduced in large fetuses with obesity. Hyperfunction of all zones of the adrenal cortex was also revealed in them. In medium height fetuses with obesity hypofunction of the thyroid gland, as well as hyperfunction of the fascicular and fetal adrenal cortex zones were present. Correlation-regression analysis has revealed close interrelations between the functional state of the thyroid gland, adrenal cortex and fetal mass.

Adrenal Cortex↗

[2 interconvertible forms of L type pyruvate kinase from the rabbit adrenal cortex].

Pyruvate kinase (PK-II) isoenzyme from rabbit adrenal cortex was isolated by chromatography on DEAE-cellulose during long-term incubation in the cold. The enzyme is resistant to fructose-1,6-diphosphate (FDP) and L-alanine. Dithiotreitol and preincubation for 10 min. at 30 degrees C did not change the resistance of the enzyme to these factors. Preincubation for 30 min. at 30 degrees C in the presence of EDTA (3.3 mM) converted the enzyme into the FDP-sensitive form, the dependency curve of the initial reaction rate on the concentration of phosphoenolpyruvate being S-form. Sucrose and dithiotreitol contributed the isolation of PK-II from rabbit adrenal cortex in the form having a higher degree of the interaction of active sites.

Adrenal Cortex↗

A preliminary study of acetylcholinesterase-positive innervation in the human adrenal cortex.

We have examined the distribution of probable cholinergic nerves in the human adrenal cortex using acetylcholinesterase (AChE) histochemistry. Adrenal tissue was obtained from three subjects during therapeutic radical nephrectomy for renal neoplastic disease. Light microscopy revealed a heterogeneous pattern of cortical innervation, with nerves most abundant in the head and body and largely absent from the tail. There was frequently a subcapsular plexus of interwoven AChE + ve nerve trunks in close relationship to densely stained (ganglion) cells. Nerves also traversed the zona fasciculata in radial trunks and a further plexus with ganglion cells was observed in the zona reticularis. Nerve trunks were seen to penetrate the medulla. Some nerve trunks appeared to terminate or branch or form individual nerve fibres (often with varicosities) which ramified through the cortical parenchyma. In the medulla, a generalised granular staining was superimposed on nerve trunks which were branched and interwoven to form a plexus around ganglion cells. The presence and distribution of AChE + ve nerve plexuses and varicose nerve fibres is suggestive of a functional intrinsic, probably cholinergic, innervation to the human adrenal cortex, perhaps derived from the splanchnic nerves.

Acetylcholinesterase↗

Localization of P450aldo and P45011 beta in normal and regenerating rat adrenal cortex.

A novel layer of cells that do not contain both P450aldo and P45011 beta has been discovered between the zonae glomerulosa and fasciculata of the rat adrenal cortex. Since P450aldo and P45011 beta are the enzymes responsible for the formation of aldosterone and corticosterone, respectively, the cells in that zone are presumably inert in synthesizing both aldosterone and corticosterone, in other words, the layer is composed of cells that have no zone-specific endocrine function as an adrenocortical component. Cytologically, the layer consists of tightly packed cells, which contain a lesser amount of lipid droplet than the cells in the other zones, and appears as a white ring or a white zone in the double immunostaining with anti P450aldo and anti P45011 beta. Upon angiotensin II-stimulation evoked by Na-deficiency, the number of the zona glomerulosa cells expressing P450aldo increases for the initial 2 or 3 days and then the P450aldo-containing zona glomerulosa cells begin to proliferate. Thus angiotensin II serves as a proliferator of the zona glomerulosa cells of the rat adrenal cortex. During the period, the thickness of the white zone decreases for initial 3 days and becomes constant after 5 or 6 days, being about 5% of the total cell number of the adrenal cortex. When localization of replicating cells was examined in the adrenal cortex, they were found to be concentrated in and around the white zone. Then the pulse-chase experiments with BrdU showed that the labeled cells migrated out of the white zone and into the zonae fasciculata and reticularis. The localization of the replicating cells in the regenerating adrenal cortex was also around the region between the zonae glomerulosa and fasciculata. On the basis of these findings, we suggest that the newly discovered cell layer (the white zone) is the stem cell zone of the rat adrenal cortex.

Adrenal Cortex↗