Search Results

You are looking at 1 - 10 of 2,335 items for

  • Abstract: Mineralocorticoids x
  • Abstract: Aldosterone x
  • Abstract: Sodium x
  • Abstract: Cortisol x
  • Abstract: Hypertension x
  • Abstract: Adrenal x
  • All content x
Clear All Modify Search
Restricted access

Renaud Beauwens, Marion Birmingham, and Jean Crabbé

The effects on sodium transport of several steroids physiologically secreted or possibly involved in pathological disorders were compared with those of aldosterone in the isolated toad skin.

The 18-hydroxylated derivatives of deoxycorticosterone and corticosterone, in contrast to their parent compounds, significantly enhanced sodium transport at a concentration of 50 nmol/l. In the presence of glucose, 18-hydroxydeoxycorticosterone increased trans-epithelial potential difference, as did aldosterone. The 19-nor derivative of deoxycorticosterone, recently implicated in the aetiology of adrenal regeneration hypertension, stimulated sodium transport, unlike 19-nor-corticosterone and 16-oxo-androstenediol. Insulin significantly increased sodium transport in aldosterone-treated skin and lowered the resistance. The natriferic response to vasopressin was potentiated fivefold by exposure of the skin to aldosterone and was doubled in skin exposed to 19-nor-deoxycorticosterone.

We conclude that 18-hydroxylated adrenocortical steroids can play a physiological role in salt retention; furthermore, these steroids, as well as 19-nor-deoxycorticosterone, could be involved in pathological conditions such as low renin hypertension. Caution should be exercised in evaluating mineralocorticoid potency solely in terms of the urinary sodium to potassium ratio.

Restricted access

P J Fuller and S Lim-Tio

The role of aldosterone in regulating epithelial sodium transport is well established as is the concept of a specific intracellular aldosterone or mineralocorticoid receptor (MR). Specific details on the molecular mechanism of this well-characterized physiology have, however, remained sketchy. Two recently published studies offer important insights into two separate aspects of aldosterone action (Shimkets et al. 1994, Wilson et al. 1995). As in many other areas of biology, naturally occurring mutations have again provided key insights.

The syndrome of apparent mineralocorticoid excess (AME) was first characterized by Ulick et al. in 1979. The condition presents in childhood with hypertension, severe hypokalaemic alkalosis, low plasma renin activity and low circulating levels of aldosterone. Treatment with the MR antagonist spironolactone is effective, paradoxically suggesting mineralocorticoid excess. That this condition could be due to a failure of the metabolism of cortisol to cortisone in aldosterone target tissues, such as the kidney or the

Free access

Ying-Ying Tsai, William E Rainey, and Wendy B Bollag

Aldosterone, secreted by the adrenal zona glomerulosa, enhances sodium retention, thus increasing blood volume and pressure. Excessive production of aldosterone results in high blood pressure and contributes to cardiovascular and renal disease, stroke and visual loss. Hypertension is also associated with obesity, which is correlated with other serious health risks as well. Although weight gain is associated with increased blood pressure, the mechanism by which excess fat deposits increase blood pressure remains unclear. Several studies have suggested that aldosterone levels are elevated with obesity and may represent a link between obesity and hypertension. In addition to hypertension, obese patients typically have dyslipidemia, including elevated serum levels of very low-density lipoprotein (VLDL). VLDL, which functions to transport triglycerides from the liver to peripheral tissues, has been demonstrated to stimulate aldosterone production. Recent studies suggest that the signaling pathways activated by VLDL are similar to those utilized by AngII. Thus, VLDL increases cytosolic calcium levels and stimulates phospholipase D (PLD) activity to result in the induction of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression. These effects seem to be mediated by the ability of VLDL to increase the phosphorylation (activation) of their regulatory transcription factors, such as the cAMP response element-binding (CREB) protein family of transcription factors. Thus, research into the pathways by which VLDL stimulates aldosterone production may identify novel targets for the development of therapies for the treatment of hypertension, particularly those associated with obesity, and other aldosterone-modulated pathologies.

Free access

Kelly De Sousa, Alaa B Abdellatif, Rami M El Zein, and Maria-Christina Zennaro

Primary aldosteronism (PA) is the most common form and an under-diagnosed cause of secondary arterial hypertension, accounting for up to 10% of hypertensive cases and associated to increased cardiovascular risk. PA is caused by autonomous overproduction of aldosterone by the adrenal cortex. It is mainly caused by a unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Excess aldosterone leads to arterial hypertension with suppressed renin, frequently associated to hypokalemia. Mutations in genes coding for ion channels and ATPases have been identified in APA, explaining the pathophysiology of increased aldosterone production. Different inherited genetic abnormalities led to the distinction of four forms of familial hyperaldosteronism (type I to IV) and other genetic defects very likely remain to be identified. Somatic mutations are identified in APA, but also in aldosterone-producing cell clusters (APCCs) in normal adrenals, in image-negative unilateral hyperplasia, in transitional lesions and in APCC from adrenals with bilateral adrenal hyperplasia (BAH). Whether these structures are precursors of APA or whether somatic mutations occur in a proliferative adrenal cortex, is still a matter of debate. This review will summarize our knowledge on the molecular mechanisms responsible for PA and the recent discovery of new genes related to early-onset and familial forms of the disease. We will also address new issues concerning genomic and proteomic changes in adrenals with APA and discuss adrenal pathophysiology in relation to aldosterone-producing structures in the adrenal cortex.

Free access

John M C Connell and Eleanor Davies

Classically, aldosterone is synthesised in the adrenal zona glomerulosa and binds to specific mineralocorticoid receptors located in the cytosol of target epithelial cells. Translocation of the resulting steroid receptor complex to the cell nucleus modulates gene expression and translation of specific ‘aldosterone-induced’ proteins that regulate electrolyte and fluid balance. However, non-epithelial and rapid non-genomic actions of aldosterone have also been described that account for a variety of actions of aldosterone that contribute to blood pressure homeostasis. These include key actions on endothelial cells and on cardiac tissue.

There is also evidence that aldosterone can be synthesised in other tissues; the most convincing evidence relates to the central nervous system. However, suggestions that aldosterone is produced in the heart remain controversial, and adrenal derived aldosterone is the principal source of circulating and locally available hormone.

Recent studies have shown major therapeutic benefits of mineralocorticoid receptor antagonism in cardiac failure, which emphasise the importance of aldosterone in causing adverse cardiovascular pathophysiological effects. Additional evidence demonstrates that aldosterone levels predict development of high blood pressure in normotensive subjects, while it is now clear that increased aldosterone action contributes to hypertension and cardiovascular damage in approximately 10% of patients with established hypertension.

These new findings highlight the role of aldosterone as a key cardiovascular hormone and extend our understanding of its role in determining adverse cardiovascular outcomes.

Free access

A L Markel, O E Redina, M A Gilinsky, G M Dymshits, E V Kalashnikova, Yu V Khvorostova, L A Fedoseeva, and G S Jacobson

The functions of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems were studied in rats with inherited stress-induced arterial hypertension (ISIAH strain). A characteristic feature of the ISIAH strain is an increase in arterial blood pressure measured both under basal conditions and after restraint stress in particular. In the control ISIAH rats, the basal plasma ACTH concentration was slightly lower than that in the normotensive Wistar albino Glaxo (WAG) rats, and no differences were found in plasma corticosterone. However, the 0.5-h restraint stress produced higher activation of the adrenal cortex in the ISIAH rats. Gluco- and mineralocorticoid responses to the blood volume reduction stresses and ACTH and corticosterone responses to social stress were stronger in the ISIAH than in the control WAG rats. An increase in epinephrine content in adrenals in the basal state and enhanced response of the sympathetic adrenal medullary system to handling stress were observed in the ISIAH rats. Restraint stress produced significantly higher expression of genes encoding corticotropin-releasing hormone-mRNA in hypothalamus and proopiomelanocortin-mRNA in pituitary in the ISIAH than in the WAG rats. Restraint stress produced a decrease in glucocorticoid receptor (GR) gene expression (GR-mRNA) in hippocampus in the ISIAH, but not in the WAG rats. A persistent increase in tyrosine hydroxylase-mRNA in adrenals of the ISIAH rats was found. It is concluded that the ISIAH rat strain is an appropriate model of stress-sensitive hypertension with the predominant involvement of the hypothalamic adrenal cortical and sympathetic adrenal medullary systems in its pathogenesis.

Restricted access



A case is described in which the presence of an adrenal cortical adenoma was predicted from the association of hypertension, hypokalaemia, raised aldosterone secretion and depressed plasma renin concentration.

Pre-operatively, administration of a spironolactone for a period of 10½ months corrected the electrolyte abnormalities, increased the plasma renin concentration to normal and lowered the blood pressure, although the raised aldosterone secretion was unchanged.

At operation a typical adrenal cortical adenoma was found.

Renal biopsy at operation showed arteriolar fibrinoid lesions, although no retinal lesions were seen at any stage.

Restricted access

M. Haji, Y. Nishi, S. Tanaka, M. Ohashi, K. Sekiya, Y. Hasegawa, M. Igarashi, S. Sasamoto, and H. Nawata


We have studied the production and release of inhibin-like immunoreactivity in the human adrenal gland. Extract of human adrenal glands showed a displacement curve paralled with the inhibin standard. Inhibin-like immunoreactivity contents in the adrenal gland was 1893±474 (mean±S.D.) IU/g wet weight tissue. ACTH stimulated the secretion of inhibin-like immunoreactivity as well as cortisol and aldosterone in a dose-dependent manner in the cultured adrenal cells. These results indicate that the human adrenal gland produces and secretes inhibin-like peptide in response to ACTH.

Restricted access



1. The characteristic response of the autotransplanted adrenal gland of the sheep to sodium depletion was an increase in aldosterone secretion rate, which reached the minimum detectable level of 1 μg/hr 6–12 hr after the Na balance became negative, when the Na deficit was approx. 200 m-equiv.

2. After its initial detection, aldosterone secretion altered in an irregular manner to maximum secretion rates of 5–9 μg/hr.

3. The initial detection of aldosterone secretion was not accompanied by any consistent changes in cortisol and corticosterone secretion.

4. Changes in cortisol and corticosterone secretion rates were usually in the same direction and of similar relative magnitude, and did not show any consistent correlation with the aldosterone secretion rates. The rates of cortisol and corticosterone secretion were extremely variable, but there was inconclusive evidence that there may have been a natural periodic variation of secretion rate, characteristic for individual sheep, which was modified by the experimental procedure.

5. The relationship between adrenal corticosteroid secretion and changes in blood plasma and urine electrolytes as well as haematocrit, plasma protein concentration and adrenal blood flow was examined.

6. Attention is drawn to the possible complexity of the relationship between adrenal corticosteroid secretion and the salivary Na/K ratio.

Free access

Yewei Xing, Michael A Edwards, Clarence Ahlem, Mike Kennedy, Anthony Cohen, Celso E Gomez-Sanchez, and William E Rainey

The adrenal glands are the primary source of mineralocorticoids, glucocorticoids, and the so-called adrenal androgens. Under physiological conditions, cortisol and adrenal androgen synthesis are controlled primarily by ACTH. Although it is well established that ACTH can stimulate steroidogenesis in the human adrenal gland, the effect of ACTH on overall production of different classes of steroid hormones has not been defined. In this study, we examined the effect of ACTH on the production of 23 steroid hormones in adult adrenal primary cultures and 20 steroids in the adrenal cell line, H295R. Liquid chromatography/tandem mass spectrometry analysis revealed that, in primary adrenal cell cultures, cortisol and corticosterone were the two most abundant steroid hormones produced with or without ACTH treatment (48 h). Cortisol production responded the most to ACTH treatment, with a 64-fold increase. Interestingly, the production of two androgens, androstenedione and 11β-hydroxyandrostenedione (11OHA), that were also produced in large amounts under basal conditions significantly increased after ACTH incubation. In H295R cells, 11-deoxycortisol and androstenedione were the major products under basal conditions. Treatment with forskolin increased the percentage of 11β-hydroxylated products, including cortisol and 11OHA. This study illustrates that adrenal cells respond to ACTH through the secretion of a variety of steroid hormones, thus supporting the role of adrenal cells as a source of both corticosteroids and androgens.