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Growth factor regulation of adrenal cortex growth and function.

The control of adrenal cortex growth in vivo during development or under certain stress conditions is still very poorly understood at the molecular level. Some information can be collected however from in vitro experiments. Acidic and basic FGF appear to be the most potent mitogens, so far, for primary cultures of adult adrenocortical cells, whereas EGF can also stimulate growth of fetal cells. Several growth factors have emerged in the recent years as multifunctional molecules that play important regulatory functions on adrenocortical steroidogenesis. These include EGF, IL-1, insulin, IGF-1 and TGF beta. In certain cases (e.g. IGF-1, TGF beta), these factors participate in autocrine loops of regulation. The differential expression, release and activation of these factors might locally regulate the steroidogenic action of the hormonal signals delivered through the hypothalamo-pituitary-adrenal axis.

Adrenal Cortex↗

[Adrenal cortex in experimental carcinogenesis of the intestine].

Morphological and histochemical examinations of the adrenal cortex of 150 rats with intestinal carcinogenesis caused by 1,2-dimethylhydrasine, and comparison of the results with control results in 20 intact rats showed the latent period to occur against the background of atrophic changes in the cortical matter consisting in a decrease in the adrenal weight, narrowing of the cortical matter, decreasing diameter of the secretory cells nuclei, accumulation of lipids and cholesterol in zona fasciculata and zona reticulosa, and decreased content of ascorbic acid. In contrast, the period of tumour growth within the intestinal mucosa coincides with hypertrophic changes in the adrenal cortex. In extensive cancer, the intensity of these hypertrophic changes increased, and dystrophically changed cells and micronecroses appeared.

Adrenal Cortex↗

Non-functioning tumours of the adrenal cortex.

Twelve cases of non-functioning adrenal tumours are presented. All were discovered incidentally during radiological investigation of abdominal conditions or staging of known malignancies. Adrenal tumours in patients with known malignancies are not necessarily metastases. Size remains the most important factor in determining their management and tumours larger than 3.5 cm should be operated on because of the possibility of malignancy. Smaller tumours should be assessed by computed tomography (CT) every 3 months for 1 year. Any change in contour, margin, density or hormone function during the follow-up period indicates the need for surgery.

Adrenal Cortex↗

Angiogenesis in human normal and pathologic adrenal cortex.

The angiogenic phenotype of 13 normal adrenal glands (N), 13 aldosterone-producing adenomas (APA), 12 cortisol-producing adenomas (CPA), 13 nonfunctioning adrenal cortical adenomas (NFA), and 13 adrenal cortical carcinomas (CA) was investigated. Intratumoral vascular density was explored by CD34, a marker of endothelial cells, and the angiogenic status was investigated by vascular endothelial growth factor (VEGF) expression, an important angiogenic factor expressed by tumoral cells. Vascular density, quantified as the number of vessels per square millimeter, was significantly lower (P < 0.0001) in CA (110.3 +/- 27.8) than in N (336.6 +/- 14.5), APA (322.8 +/- 19.1), CPA (288.5 +/- 14.3), and NFA (274.2 +/- 19.8). VEGF expression, calculated as the percentage of positive cells, was significantly greater (P < 0.0001) in CA (85.3 +/- 2.1) than in APA (56.5 +/- 7.5), CPA (38.5 +/- 7.0), N (33.1 +/- 6.1), and NFA (0.76 +/- 0.6). In APA, a negative relation between CD34 and plasma renin activity (P < 0.0002) and a positive association between CD34 and aldosterone levels (P < 0.05) was found. In conclusion, the angiogenic phenotype of CA is characterized by VEGF overexpression but low vascularization, a finding suggesting a dissociation between angiogenic potential and neoangiogenic capabilities of these tumors. The lack of VEGF expression in NFA and the close association between angiogenesis and functional status in APA also suggest a possible influence of the angiogenic phenotype on hormonal secretion of these endocrine tumors.

Adenoma↗

Developmental changes in steroidogenic enzymes in human postnatal adrenal cortex: immunohistochemical studies.

Adrenarche is considered to occur as a result of intra-adrenal changes in steroidogenic enzymes involved in C19 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), 17alpha hydroxylase (P450c17), dehydroepiandrosterone sulfotransferase (DHEA-ST), P450 oxidoreductase, cytochrome b5, and 3beta-hydroxysteroid dehydrogenase (3betaHSD) 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. 3betaHSD 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 3betaHSD in the reticularis is likely to contribute to increased C19 steroid production during adrenarche.

3-Hydroxysteroid Dehydrogenases↗

[Histological and ultrastructural analysis of the adrenal cortex of the Wrangel Island hoofed lemming (Dicrostonyx torquatus vinogradovi Ognev, 1948)].

Structure of the adrenal cortex of the lemming (Dicrostonyx torquatus vinogradovi Ognev, 1948) from the Wrangel Island has been studied light optically and electron microscopically. Histological investigation of the adrenals has revealed some peculiar features in the gland demonstrating a moderate development of the reticular zone in both sex in the Dicrostonyx torquatus, as well as certain sex dimorphism in the organ's structure. A smaller specific gravity of the female glomerular zone, division of the female glomerular zone into two morphologically heterogenous layers and more distinctive medullary capsule in the males should be mentioned as the distinctive features. During pregnancy the glomerular zone undergoes certain reduction, while the glomerulo-reticular zone hypertrophizes. Electron microscopically it has been revealed: lack of the specific vesicular structure in the mitochondrial crists in the fascicular zone cells, an increased contents of myelin-like and vascular formations in mitochondria of the fascicular and reticular zones, a large amount of dark degenerating cells in the reticular zone, as well as a moderate amount of liposomes in corticocytes. Owing to these factors, it is possible to suggest an increased level of steroid processes in the lemming adrenal cortex.

Adrenal Cortex↗

[Functional and morphologic investigations of the human adrenal cortex in various diseases].

The paper is devoted to investigations of the human adrenal cortex on autopsy material obtained 1 h after death. The purpose was to study the features of 3 cortical zones in some diseases with relation to sex and age. Quantitative histoenzymological analysis was used, metabolic indices of corticocytes and the cortical microvascular wall in 3 functionally differentiated zones (glomerular, fascicular and reticular) were estimated. Histoenzymological reactions were subjected to cytospectrophotometric analysis with subsequent statistical processing of data array. Age-related features of the adrenal cortex differed considerably among men and women, and were associated with corticocytes as well as with the cortical microvascular wall. There was no age-related decrease in enzymatic activity in all the adrenocortical structures but there was change in the interrelationship among the 3 differentiated zones. In some diseases change of enzymatic activity proper was noted in all the zones however a histotopogram of the cortex typical of a given age, was preserved. Functional and morphological investigations permitted assessment of the rearrangement of intraadrenal homeostasis, reflecting, probably, shifts in the synthesis of the main 3 classes of corticosteroid hormones.

Adrenal Cortex↗

Development of adrenocortical failure in non-Addisonian patients with antibodies to adrenal cortex. A clinical follow-up study.

Out of 1036 sera tested for the presence of antibodies to adrenal cortex using the indirect immunofluorescence (IFL) method, fifteen out of 323 patients with Graves' thyrotoxicosis, 6/105 Hashimoto's thyroiditis, 3/29 myxoedema, 2/49 asymptomatic autoimmune thyroiditis, 1/12 subacute thyroiditis, and 4/130 with myasthenia gravis were positive. Thirty antibody-positive non-addisonian patients were tested for subclinical adrenocortical failure and followed up over a period of 1-3.5 years. Three women with Graves' disease had biochemical signs of early Addison's disease at the first Synacthen test. Two young women with controlled Graves' thyrotoxicosis developed a diminished adrenocortical reserve within 2 and 3 years, respectively; one of them developed anovulatory cycles which did not respond to clomiphene treatment. Both patients had high titres of complement-fixing adrenal antibodies before the adrenal failure could be recognized by functional tests. One elderly female patient in whom a euthyroid goitre with adrenal and thyroid antibodies was detected in 1977, developed Graves' thyrotoxicosis in 1980. These observations indicate that antibodies to adrenal cortex have a high clinical significance and may allow the early diagnosis of Addison's disease even in the absence of specific clinical symptoms.

Addison Disease↗

An ELISA method for the detection of autoantibodies to adrenal cortex.

An enzyme-linked immunosorbent assay (ELISA) is described for autoantibodies to adrenal cortex. Microsomes were prepared from fresh human adrenal glands, and microtitre ELISA plates were incubated at 4 degrees C overnight with 25 micrograms antigen/ml, the optimal concentration for the system. Optimal dilution of patient's serum was 1/500. Peroxidase-labelled anti-human IgG and IgM sera were used in separate tests and o-phenylenediamine and H2O2 served as substrate. Intra-assay variance of optical density units was 4.5%, and inter-assay variance was negligible when antigen preparations from 2 different adrenal glands were compared. All sera positive or negative at first test gave the same qualitative result in a second. Non-organ-specific binding of sera containing mitochondrial or ribosomal antibodies was eliminated by a blocking ELISA system where the antigen-coated plates were incubated with test sera, and in a second step, peroxidase-labelled IgG from an adrenal antibody-positive control serum was added. In this test, optimal antigen concentration for coating of plates was 6.25 micrograms/ml and optimal serum dilution 1/50. The ELISA proved more sensitive and reproducible than indirect immunofluorescence. Adrenal antibodies detected by ELISA were usually of IgG class alone and only 1 of the 30 positives also contained IgM specificity. 30 out of 38 sera (79%) from patients with 'idiopathic' Addison's disease were positive whereas immunofluorescence revealed only 23 (61%) at first testing and another 4 positives when sera were tested on different adrenal glands. The ELISA described is useful for both scientific work and clinical diagnosis of autoimmune adrenalitis.

Adrenal Cortex↗

Influence of oxytocin on the steroidogenic activity of rat adrenal cortex.

The aim of the present study was to investigate the changes in the morphology and 3beta-hydroxysteroid dehydrogenase activity of the cells of the rat adrenal cortex after single and long-term in vivo treatment with oxytocin. Sexually mature male Wistar rats (n = 12) divided into three groups were used in the study. Group 1 were rats that received a single treatment with oxytocin (0.25 IU/100g wet weight, subcutaneously); group 2 included rats that were treated with oxytocin (0.25 IU/100 g wet weight, subcutaneously) for a period of 10 days; and group 3 were the control animals treated with saline solution. The activity of 3beta-hydroxysteroid dehydrogenase, mainly from the adrenal cortex, was examined on fresh cryostat sections (6 mm). Single treatment with oxytocin increased the enzyme activity of the adrenal cortex cells, especially in the cells of zona gromerulosa and zona fasciculata, while in long-term treatment inhibition of the enzyme activity was present. The results obtained demonstrate the changes induced in the enzyme activity of the adrenocorticocytes after treatment with oxytocin and suggest the role of this neuropeptide in the local regulation of the adrenal function.

3-Hydroxysteroid Dehydrogenases↗