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Quantitative ultrastructural study of the rat adrenal cortex in renal encapsulation-induced hypertension.

Hypertension was induced in young rats by latex encapsulation of both kidneys. By the fourth week, 85% of the renal-encapsulated (RE) rats became hypertensive. Varying degrees of cardiovascular involvement were evident in the moderately to severely hypertensive rats. The level of systolic blood pressure was directly correlated with the width and the volume of zona glomerulosa of the adrenal cortex. Electron microscopy combined with morphometric-stereologic techniques was employed to quantitate change in the adrenal cortex. The cells of both zona glomerulosa and zona fasciculata of RE rats showed significant increases in the volume of the cell, nucleus, smooth endoplasmic reticulum, and lipid droplets; only in the zona glomerulosa cells was the increase in surface area of the smooth endoplasmic reticulum statistically significant. It is suggested that these structural changes associated with renal-encapsulation hypertension are related at least in part to stress of the hypertensive cardiovascular disease.

Adrenal Cortex↗

Immunohistochemical expression of insulin-like growth factor 1 and its receptor in normal and neoplastic human adrenal cortex.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) may influence cellular growth, differentiation and secretion. MATERIAL AND METHODS: Cryosectioned normal human adrenal glands (n = 6), cortical adenoma (n = 21), and carcinoma (n = 17) were stained immunohistochemically for IGF-1 and its receptor, and human adrenocortical cancer cells expressing the receptor were analysed for influences on proliferation. RESULTS: Normal cortical parenchyma generally displayed faint IGF-1 reactivity and intracellular receptor staining. Similar labelling encompassed the adenomas, but only 6 of them were receptor reactive. IGF-1 expression was conspicuous in 11 carcinomas, and 6 of them displayed cell surface receptor reactivity. All aldosterone producing lesions were receptor antibody unreactive. Recombinant IGF-1 dose-dependently stimulated the cell proliferation, and this effect was reversed by the receptor antibody. CONCLUSION: IGF-1 may interact with function and proliferation of the human adrenal cortex with particular reference to cortical carcinomas lacking discernible aldosterone excess.

Adenoma↗

Zonal variation in the distribution of an alpha 1-acid glycoprotein glycoform receptor in human adrenal cortex.

Using a histochemical technique with three different alpha 1-acid glycoprotein glycoform one glycoform specific receptor has been identified in human adrenal cortex. The receptor is associated to alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C. The glycoform specific receptor was located in the cytoplasm of glomerulosa and outer fasciculata cells. The intensity of the reaction product decreased in the fasciculata, and no staining was seen in inner fasciculata and reticularis. Inhibition with the simple sugars, mannose and GlcNAc confirmed a lectin-like reaction. The binding activity was dependent on the presence of calcium ions and not on thiol reagents. Thus the lectin-like receptor may belong to the C-type lectin family. Using an antibody to alpha 1-acid glycoprotein the presence of alpha 1-acid glycoprotein was observed in the same location as the glycoform specific receptor. The binding of alpha 1-acid glycoprotein glycoform B and alpha 1-acid glycoprotein glycoform C to the glycoform specific receptor is inhibited by the steroid hormones cortisone, aldosterone, estradiol and progesterone but not by testosterone. The pronounced changes in the distribution of AGP and its glycoform receptors during cell differentiation in the adrenal cortex suggest that AGP and its complementary lectins belong to the group of lectins which control differentiation and spatial position.

Adrenal Cortex↗

Mitochondrial steroid metabolism in the inner and outer zones of the guinea-pig adrenal cortex.

Previous investigations have demonstrated that cells isolated from the outer zone (zona fasciculata + zona glomerulosa) of the guinea-pig adrenal cortex produce far more cortisol than those from the inner zone (zona reticularis). Studies were carried out to compare mitochondrial steroid metabolism in the two zones. Protein and cytochrome P-450 concentrations were similar in outer and inner zone mitochondria. However, the rate of 11 beta-hydroxylation was significantly greater in the outer zone despite the fact that substrates for 11 beta-hydroxylation (11-deoxycortisol, 11-deoxycorticosterone) produced larger type I spectral changes in inner zone mitochondria. The apparent affinities of 11-deoxycortisol and 11-deoxycorticosterone for mitochondrial cytochrome(s) P-450 were similar in the two zones. In both inner and outer zone mitochondria, 11 beta-hydroxylation was inhibited by metyrapone but unaffected by aminoglutethimide. Cholesterol sidechain cleavage activity, measured as the rate of conversion of endogenous cholesterol to pregnenolone, was far greater in outer than inner zone mitochondria. Addition of exogenous cholesterol or 25-hydroxycholesterol to the mitochondrial preparations did not affect pregnenolone production in either zone. Addition of pregnenolone to outer zone mitochondria produced a reverse type I spectral change (delta A 420-390 nm), suggesting displacement of endogenous cholesterol from cytochrome P-450. In inner zone mitochondria, pregnenolone induced a difference spectrum (delta A 425-410 nm) similar to the reduced vs oxidized cytochrome b5 spectrum. A b5-like cytochrome was found to be present in the mitochondrial preparations. Prior reduction of the cytochrome with NADH eliminated the pregnenolone-induced spectral change in inner zone mitochondria but had no effect in outer zone preparations. The results suggest that differences in mitochondrial steroid metabolism between the inner and outer adrenocortical zones account in part for the differences in cortisol production by cells in each zone.

Adrenal Cortex↗

Chromaffin cells in the glomerular zone of adult rat adrenal cortex.

The occasional presence of islets of chromaffin cells in the glomerular zone of the adrenal cortex of adult rats, is reported in this light and electron microscope study. A possible error in organogenesis of the gland and the possible persistence of some foetal characteristics in these ectopic cells are discussed.

Adrenal Cortex↗

The histogenesis of the rat adrenal cortex: a study based on histologic analysis of mosaic pattern in chimeras.

A series of chimeric rats was used to investigate the histogenesis of the adrenal cortex. These animals were produced by amalgamating preimplantation embryos of two congenic strains which express different alloantigens of the major histocompatibility system. The manner in which cells assort themselves during embryogenesis and organ renewal is amenable to analysis by using radiolabeled antibodies directed to the class I antigens. Mosaic pattern analysis of the adrenal cortex of these rats revealed that a clonal pattern of division was maintained across all three histogenic zones of the organ, even in highly unbalanced chimeric combinations. No apparent relationship existed between the proportion of cell types and the area of contiguously similar lineage (patch size). In the series examined, the percentage of cells derived from the PVG-RT1a lineage varied from 5 to 85%. The number of parallel cords varied from 6 to 28. The pattern analysis of informative corners of cross sections of the gland supports the thesis that organ maintenance is the result of cell division from the outside of the cortex toward the inside medullary surface.

Adrenal Cortex↗

Treatment with o,p'-DDD (mitotane) decreased cytochrome P-450, heme, and microsomal protein content in the dog adrenal cortex in vivo.

Treatment with o,p'-DDD, at a does which markedly inhibits steroidogenesis (60 mg/kg, intravenously), significantly decreased adrenal mitochondrial and microsomal "P-450" and microsomal protein contnet 34%, 55%, and 35% respectively, within 3 hours. The reduction of cytochrome P-450 content was accompanied by decrease in heme content, which explains the apparent loss of cytochrome P-450. This action provides a possible explanation for the inhibition of steroidogenesis caused by o,p'-DDD, and indicates that o,p'-DDD initiates a very destructive process in the dog adrenal cortex.

Adrenal Cortex↗

[The role of initial state of adrenal cortex in external irradiation effects upon its structure, function and androgen-receptor interactions].

We studied morphological-biochemical time-course reactions of adrenal cortex and hormonal function of testicles after combined or separate actions of external radiation exposure (1.0 Gy at 7.8 x 10(-4) Gy/sec) and prolonged (12-, 32 days) subcutaneous corticosterone injections (10 mg/kg/animal) in 2-3-month old male rats. Both variants with exogenous hormone depressed endogenous glucocorticoid production and evolved acute structure-functional adrenal gland cortex deficiency. Radiocensitivity of the gland at the experimental conditions was increased. Simultaneously the aggravation of adrenal cortex functional activity accompanied with hypogonadism and depressed reproductive potential of male rats, accessed by means of androgen status and androgenspecific (transporting and receptional) proteins characteristics as sensitive molecular markers of an animal possible fecundity.

Adrenal Cortex↗

[Effect of heparin on the ultrastructure of the fascicular and reticular zones of the adrenal cortex of rats].

The effect of a prolonged use of heparin on the ultrastructure of the zona fasciculata and zona reticulosa of the adrenal cortex was studied in experiment. Heparin was injected subcutaneously to laboratory male rats at a daily dose of 5 mg/kg. The animals were decapitated on the 5th, 10th, 30th and 60th days after heparin administration, 20 and 50 days after 10-day use of the drug and 30 days after 30-day use. In the first days of use heparin stimulated the secretory activity of cells of the zona fasciculata and zona reticulosa of the adrenal cortex. The ultrastructure of the internal area of the zona fasciculata and zona reticulosa indicated the suppression of adrenocorticocytes during the use of heparin for 30 days. In 60-day administration of heparin the ultrastructure of adrenocorticocytes was closer to the control though in cells of the zona fasciculata the content of glycogen exceeded the normal one. In cancelling the drug the adrenal structure got back to normal rather slowly.

Adrenal Cortex↗

Toxaphene: accumulation in the adrenal cortex and effect on ACTH-stimulated corticosteroid synthesis in the rat.

Uptake and distribution of [14C]toxaphene was studied in the adrenals of rats using whole-body autoradiography. An accumulation of radioactivity was seen in the adrenal cortex (zona fasciculata) 1-24 h after a single gavage of [14C]toxaphene (16 mg/kg b.w.). In in vitro studies toxaphene was found to inhibit ACTH-stimulated corticosterone synthesis in the cultured rat adrenocortical cells (IC50 2.8 X 10(-5) M). Moderate but significant inhibition (P less than 0.001) of ACTH-stimulated corticosterone synthesis was also observed in the adrenocortical cells isolated from rats after a prolonged exposure (5 weeks) to low levels (1.2 ppm) of toxaphene in feed. The results indicate a direct adrenotoxic effect of toxaphene.

Adrenal Cortex↗

BCG influence on 256 Walker carcinosarcoma growth in rats in relation to adrenal cortex status.

BCG influence on antitumoral immunity varied in relation to the timing and the way of administration, as well as in relation to the adrenal cortex status of the animals. BCG administration several days before tumor grafting, but especially when mixed with tumoral cells determined a maximum antitumoral effect, while vaccination after the tumor had been formed enhanced its metastasization. The decrease of the endogenous corticoids secretion amplified the antitumoral effect of BCG, while exogenous cortisone diminished this effect. The study of in vitro cultivated tumoral cells as well as microscopic examination of the tumors suggest the involvement of a complex process in the achievement of the nonspecific antitumoral immunity, a process in which the adrenal cortex status plays an important role.

Adrenal Cortex↗