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Isoforms of protein kinase C and their distribution in human adrenal cortex and tumors.

The cytosol and microsomal fractions of human adrenal cortex contain 3 isoforms of protein kinase C: alpha, zeta, and epsilon. The latter fraction is present in trace amounts. No isoforms beta1, beta2, gamma and delta were found in these cell fractions. The distribution of alpha-isoform between the cytosol and microsomal fraction is determined by tissue origin: in normal tissue its content differs by no more than 10%, while in most tumors this isoform is translocated into the microsomal fraction. The distribution of zeta-isoform did not depend on tissue origin.

Adrenal Cortex↗

[Quantitative evaluation of ultrastructural restructuring in the adrenal cortex of rats under stress].

Quantitative and qualitative analysis has revealed that submicroscopic changes of the rat adrenal cortex in dynamics of the stress reaction examined at the level of "functional element" which combines basic structural components of the parenchyma and stroma are of the polyphase character and agree with data from the biochemical analysis of 11-OCS in blood plasma. At the stage of exhaustion of the stress reaction (72 hours of immobilization) the ultrastructure of the adrenal cortex testifies to the preservation of functional reserves in the secretory cells.

Adrenal Cortex↗

Zonal distribution of cytochrome P-450s (P-450(11) beta and P-450scc) and their relation to steroidogenesis in bovine adrenal cortex.

Zona glomerulosa and zonae fasciculata-reticularis of bovine adrenal cortex were separated by our improved method using a remodeled microtome. A considerable amount of fresh mitochondria and microsomes was quickly obtained. Specific content of cytochrome P-450 in the mitochondria was higher in zonae fasciculata-reticularis than in zona glomerulosa. When metyrapone was added to the mitochondria and the drug-induced difference spectra were measured, there appeared two phases in the titration curve; the first phase was saturated at a concentration of 3 microM and the second phase appeared at concentrations higher than 10 microM. The first phase seemed to be due to the substrate-free P-450(11) beta and the second phase to the cholesterol-bound P-450scc. From these spectral studies contents of cytochrome P-450scc and P-450(11) beta were estimated, and those were found to be equal for each zone. From similar studies on substrate-induced difference spectra, there seemed to be no difference between two zones in the affinity of cytochrome P-450(11) beta for deoxycorticosterone and 11-deoxycortisol. This was also the case with 11 beta-hydroxylase activity and substrate specificity for deoxycorticosterone and 11-deoxycortisol.

Adrenal Cortex↗

Opposite feedback control of renin and aldosterone biosynthesis in the adrenal cortex by angiotensin II AT1-subtype receptors.

The aims of this study were to identify whether tissue renin is regulated by a negative-feedback mechanism produced by locally generated angiotensin (Ang II) in the adrenal cortex and to detect the pathway of Ang II modulation. For this purpose, in 36 12-week old, salt-restricted, nephrectomized Sprague-Dawley rats, we studied the effects of the Ang II AT1-subtype receptor antagonist losartan and of the Ang II AT2-subtype receptor antagonist PD123319 on renin mRNA and activity, aldosterone synthase mRNA, and AT1a-, AT1b-, and AT2-subtype receptor expression in the adrenal cortex. Ten additional rats, kept on a regular diet and then nephrectomized, were also studied. In salt-restricted, nephrectomized rats, losartan administration caused increases of adrenal renin mRNA (P<.05) and activity (P<.05) and a concomitant reduction of aldosterone synthase mRNA (P<.05). In addition, after losartan AT1b, receptor mRNA was reduced (P<.05), AT1a receptor mRNA was unchanged, and AT2 mRNA was increased (P<.05). PD123319 did not significantly modify any of these parameters. In conclusion, in salt-restricted, nephrectomized rats, selective antagonism of AT1-subtype receptors stimulates the expression and the activity of renin in the adrenal cortex. This observation demonstrates that Ang II locally formed in the adrenal cortex exerts a modulatory negative-feedback action on adrenal renin biosynthesis independent of the influence of the circulating renin-Ang system; this action is largely mediated through the AT1b-subtype receptors.

Adrenal Cortex↗

Isopycnic density values for lysosomes and mitochondria in rat adrenal cortex.

Adrenocortical tissues of male adult Wistar rats were fractionated by isopycnic density gradient centrifugation. Fractions were analyzed for density, protein and marker enzymes for lysosomes and mitochondria with rat liver being used as a reference tissue for subcellular enzyme distribution. Both lysosomes and mitochondria of adrenal cortex showed unimodal distribution profiles of marker enzymes with their modal isopycnic density values at 1.165. This value was significantly lower than the corresponding ones for lysosomes and mitochondria in rat liver but was very close to those in porcine adrenal cortex. Modal isopycnic density as well as distribution profiles of marker enzymes for lysosomes and mitochondria remained unchanged 24 hr after 0.1 or 10 units of ACTH (Cortrosyn Z) administration. As in porcine adrenal cortex, lysosomes in rat adrenal cortex were characterized by a higher content of cathepsin D than those in rat liver.

Adrenal Cortex↗

Transforming growth factor alpha, epidermal growth factor, and epidermal growth factor receptor expression in normal and diseased human adrenal cortex by immunohistochemistry and in situ hybridization.

Because epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), and epidermal growth factor receptor (EGFR) have been implicated in the regulation of adrenocortical function, we used immunohistochemistry and in situ hybridization of EGF and TGF-alpha to study 41 specimens of human adrenal cortex, including 10 normal specimens, 15 aldosteronomas, five Cushing's adenomas, six adrenocortical incidentalomas, and five carcinomas to determine what role these growth factors play in controlling human adrenocortical function. Neither immunoreactivity nor mRNA hybridization signals to EGF was detected in any specimens, and EGF therefore may exert its effects on adrenal function as an endocrine hormone. TGF-alpha expression was detected at both protein and mRNA levels in normal and neoplastic adrenal cortex, demonstrating that TGF-alpha is synthesized locally in human adrenal cortex. TGF-alpha expression was observed in the cells with increased steroidogenesis, including compact tumor cells and zona fasciculata cells with lipid depletion, but did not necessarily correlate with production sites of any specific steroid hormone. EGFR immunoreactivity was more widely distributed than TGF-alpha immunoreactivity. Both TGF-alpha and EGFR expression were markedly elevated in adrenocortical carcinomas. TGF-alpha and EGFR thus appear to be involved in biological function in both normal and neoplastic human adrenal cortex. In addition, TGF-alpha and EGFR may play important roles in some biological features of adrenocortical malignancy.

Adrenal Cortex↗

[Cucurbitacin R glycoside--a regulator of steroidogenesis and of the formation of prostaglandin E2--a specific modulator of the hypothalamus-hypophysis-adrenal cortex system].

2 beta,25-di(0-beta-D-glucopyranosyloxy)-16 alpha,20-dihydroxycucurbit-5-en-3,11,22-trione (cucurbitacin R glucoside--CRG), isolated from Bryonia alba roots, stimulates corticosterone secretion in the adrenal cortex of rats and augments the working capacity of mice. If rats after CRG injections were exposed to immobilization stress, the level of corticosterone in the adrenal cortex and blood plasma was not increased, like in the control groups of rats not receiving CRG. The level of prostaglandin E2 in the adrenal cortex was increased during stress and after CRG administration. These findings indicate that CRG regulates steroidogenesis by influencing the activity of prostaglandin G2-prostaglandin E2 isomerase.

Adrenal Cortex↗

[Myelolipoma of the adrenal cortex].

It is reported on a 45-year-old patient suffering from a great myelolipoma of the Adrenal cortex which was suspected as retroperitoneal tumor by clinical examination and confirmed by ultrasonography and computerized tomography. The diagnosis was verified by histological investigation of the operative specimen. Pathogenetic factors are discussed and hormonal influence may possible. The benign myelolipoma of the adrenal cortex should considered in the differential diagnosis of a retroperitoneal tumor.

Adipose Tissue↗