Biomedical subjects

S Rocco

Publications and source records attributed to S Rocco.

At least 19 recordsLinked to original sources

PubMed1995

Long-term treatment of mineralocorticoid excess syndromes.

Recognition of the pathogenesis of secondary forms of hypertension is often considered the key to appropriate choice of treatment. We here present the results of a prolonged clinical follow-up (from 1 to 20 years) of a large number of patients with mineralocorticoid excess syndromes (MES), including over 100 patients with primary aldosteronism (PA), 3 cases with dexamethasone-suppressible aldosteronism (DSA), 3 cases of apparent mineralocorticoid excess (AME) Type II, and 4 patients with 17-hydroxylase deficiency (17OHDS). The patients with PA have been divided in two subgroups, one of 69 cases followed between 1973 and 1982, and the second of 37 patients studied between 1983 and 1992; 33 further cases were not evaluated due to poor compliance. In group I, 26 patients underwent surgery (23 unilateral adenoma, 1 primary hyperplasia, 2 bilateral nodular hyperplasia); at 5 years 50% had normal blood pressure, 25% had mild hypertension and 25% had moderate to severe hypertension. Forty-three patients with either adenoma (APA) or idiopathic aldosteronism (IHA) received long-term spironolactone treatment. Among them, 13 required the addition of thiazide and/or beta-blockers, while 13 were switched to an amiloride/thiazide combination (+/- beta blockers) due to side-effects to spironolactone (gynecomastia 6/20 males, menstrual upset or breast pain in 7/23 females). In group II, 12 patients underwent surgery (11 adenoma, 1 primary hyperplasia) with a similar outcome at 3 years as in group I; 25 patients were put on either K canrenoate (11) or Ca++ channel blockers (14) with or without KCl supplementation; in 8 cases these two drugs were combined according to blood pressure levels achieved during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Hyperplasia, Congenital↗

PubMed1995

Morphology and function of the adrenal zona glomerulosa of transgenic rats TGR [mREN2] 27: effects of prolonged sodium restriction.

Heterozygous female transgenic rats for the murine Ren-2 gene (TGR) display a high blood pressure, together with a low kidney and high adrenal renin content. The effects of prolonged sodium restriction on the morphology and secretory activity of adrenal zona glomerulosa (ZG) of TGR and their age- and sex-matched Sprague-Dawley control rats (SDR) were investigated. Under basal conditions, TGR had a moderately hypertrophic ZG, that showed a significantly higher secretion of 18-hydroxylated (18OH) steroids: 18-hydroxy-11-deoxycorticosterone (18OH-DOC), 18-hydroxycorticosterone (18OH-B) and aldosterone (ALDO); ZG cells of TGR showed angiotensin II (AII)-binding site concentrations and ALDO secretory responses to AII similar to those of SDR ZG cells. Prolonged sodium restriction increased plasma ALDO level in both SDR and TGR, and significantly raised the volume of ZG. ZG hypertrophy was due to the increase in both the number and average volume of its parenchymal cells. The secretion of 18OH-steroids was markedly enhanced in both groups of rats; however, in TGR this rise was exclusively due to increases of 18OH-DOC and 18OH-B, while in SDR also ALDO production was enhanced. The yield of non-18OH-steroids was not affected. 11-Dehydrocorticosterone production was not changed in SDR, but doubled in TGR. ZG cells of sodium-restricted SDR and TGR displayed similar increases in their AII-binding site concentration and ALDO secretory response to AII. In conclusion, our present findings confirm that TGR possess a hypertrophic ZG and an elevated secretory capacity o 18OH-steroids, but show only slight differences in ZG and ZG-cell responses to prolonged sodium deprivation.

Animals↗

PubMed1995

Bacterial lipopolysaccharide stimulates glucocorticoid secretion in hypophysectomized rats.

The effect of an i.p. bolus injection of 200 micrograms.kg-1 bacterial lipopolysaccharide (LPS) on the plasma concentrations of ACTH and corticosterone (B) were studied in intact and hypophysectomized/ACTH replaced (Hx) rats. Hormonal blood levels were measured by RIA, 30, 60, 120, 180 and 240 min after the injection. The stress evoked by the vehicle i.p. injection provoked significant rises in ACTH and B blood levels at 30 and 60 min in intact rats, but not in Hx animals. In intact rats, LPS enhanced (over the respective control value) ACTH plasma level at 60, 120 and 180 min, and B plasma concentration at 120, 180 and 240 min. In Hx rats, LPS did not affect ACTH blood level, but raised B plasma concentration at 60, 120 and 180 min. B response to LPS at 120 min was completely annulled, in both intact and Hx rats, by the simultaneous administration of 25 nmol.kg-1 alpha-helical-CRH and corticotropin-inhibiting peptide that are competitive inhibitors of CRH and ACTH, respectively. The hypothesis is advanced that LPS may activate hypothalamo-pituitary adrenal axis in rats, by stimulating not only the central (hypothalamo-pituitary), but also the peripheral (intra-adrenal) branch of the CRH/ACTH system.

Adrenocorticotropic Hormone↗

PubMed1995

[Primary hyperaldosteronism].

The diagnosis of primary aldosteronism (PA) is based on the finding of the combination of elevated urinary and/or plasma aldosterone and suppressed renin activity in patients with hypertension and hypokalemia. However, PA consists in a number of subsets, and diagnostic criteria for a correct identification of surgically remediable forms are of great interest. The methods and the results concerning our series of 113 patients with primary aldosteronism are presented in this review. Aldosterone producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) were the most frequent forms, 51% and 44% respectively. They had similar BP levels, but hypokalemia was most frequently found in APA. Urinary and upright plasma aldosterone were similar, but supine plasma aldosterone was lower in IHA. Plasma aldosterone response to upright posture and angiotensin II infusion was absent in most cases of APA and present in IHA, but occasionally renin-responsive adenoma were found. Captopril failed to decrease plasma aldosterone in most patients with APA, and in a subgroup of patients with IHA. Patients with adenoma had also higher values of the aldosterone precursor 18-OH-B, and of atrial natriuretic peptide (ANP), probably as a consequence of a greater degree of volume expansion. Among morphological studies, CT scan and adrenal radio-cholesterol scintiscan provided similar results (85% accuracy): adrenal vein catheterization clarified almost all the remaining cases. Among the subsets of PA, 3 familiar cases of dex-suppressible hyperaldosteronism were recognized, with characteristically high levels of aldo, 18-OH-B, 18-OH-cortisol and 18-oxo-cortisol, due to the genetic abnormalities of the 11-18 hydroxylase system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1994

Zona glomerulosa of the adrenal gland in a transgenic strain of rat: a morphologic and functional study.

Transgenic rats for the murine Ren-2 gene display high blood pressure, low circulating levels of angiotensin II, and high renin content in the adrenal glands. Moreover, transgenic rats possess an increased aldosterone secretion (maximal from 6 to 18 weeks of age), paralleling the development of hypertension. To investigate further the cytophysiology of the adrenal glands of this strain of rats, we performed a combined morphometric and functional study of the zona glomerulosa of 10-week-old female transgenic rats. Morphometry did not reveal notable differences between zona glomerulosa cells of transgenic and age- and sex-matched Sprague-Dawley rats, with the exception of a marked accumulation of lipid droplets, in which cholesterol and cholesterol esters are stored. The volume of the lipid-droplet compartment underwent a significant decrease when transgenic rats were previously injected with angiotensin II or ACTH. Dispersed zona glomerulosa cells of transgenic rats showed a significantly higher basal aldosterone secretion, but their response to angiotensin II and ACTH was similar to that of Sprague-Dawley animals. Angiotensin II-receptor number and affinity were not dissimilar in zona glomerulosa cells of transgenic and Sprague-Dawley rats. These data suggest that the sustained stimulation of the adrenal renin-angiotensin system in transgenic animals causes an increase in the accumulation in zona glomerulosa cells of cholesterol available for steroidogenesis, as indicated by the expanded volume of the lipid-droplet compartment and the elevated basal steroidogenesis. However, the basal hyperfunction of the zona glomerulosa in transgenic animals does not appear to be coupled with an enhanced responsivity to its main secretagogues, at least in terms of aldosterone secretion.

Adrenocorticotropic Hormone↗

PubMed1994

Evidence that endogenous somatostatin (SRIF) exerts an inhibitory control on the function and growth of rat adrenal zona glomerulosa. The possible involvement of zona medullaris as a source of endogenous SRIF.

The effect of SRIF and its antagonist cyclo(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr magnitude of Bzl)(SRIF-A) were studied in sham-operated and bilaterally adrenalectomized rats bearing ACTH- and angiotensin II (ANG-II)-responsive adrenocortical autotransplants. SRIF-A (10(-5) M) completely annulled SRIF (10(-6) M)-induced inhibition of ANG-II (10(-8) M)-evoked rise in aldosterone (ALDO) secretion by both dispersed zona glomerulosa (ZG) cells and autotransplant slices. A 7-day intraperitoneal infusion with SRIF (0.3 nmol.kg-1.min-1) significantly lowered plasma ALDO concentration (PAC) in both groups of animals, without affecting plasma renin activity and the plasma levels of ACTH and corticosterone. This treatment caused a marked atrophy of adrenal ZG and its parenchymal cells (without inducing any significant change in the zona fasciculata morphology), as well as of ZG-like cells of autotransplants. Isolated ZG cells and autotransplant slices from SRIF-infused rats evidenced a notable decrease in both their basal and maximally ACTH- or ANG-II-stimulated ALDO production. The simultaneous infusion of rats with SRIF-A (3 nmol.kg-1.min-1) completely reversed all these effects of SRIF. The prolonged infusion with SRIF-A alone caused, in sham-operated rats, a marked increase in PAC and a significant hypertrophy of ZG and ZG cells; basal and maximally-stimulated ALDO secretion of dispersed ZG cells was also notably raised. Conversely, SRIF-A infusion did not evoke any appreciable effect in autotransplanted rats. These findings suggest that endogenous SRIF is specifically involved in the negative control of the secretion and growth of the rat adrenal ZG. Since regenerated adrenocortical autotransplants, which are responsive to SRIF but not to SRIF-A infusion, are completely deprived of chromaffin cells, the hypothesis is advanced that adrenal zona medullaris may be the source of endogenous SRIF regulating ZG function.

Adrenal Cortex↗

PubMed1994

Glucose phosphate isomerase (GPI) "Morcone": a new variant from Italy.

Here we report the 4th Italian case of glucose phosphate isomerase (GPI) deficiency. The propositus is a young man suffering from chronic haemolytic anaemia since birth with occasional transfusion requirement. Biochemical characterization of the defective enzyme revealed increased affinity for F-6-P, decreased affinity for G-6-P and marked thermoinstability. Electrophoretic mobility appeared normal. GPI from both parents showed similar but less pronounced biochemical alterations. The variant described here seems to be different from those previously reported. Thus, we propose the provisional name of GPI "Morcone".

Adult↗

PubMed1993

Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats.

Within two weeks, hypophysectomy induced in rats a striking decrease in the level of circulating ACTH (the concentration of which was at the limit of sensitivity of our assay system), coupled with a net reduction in the plasma corticosterone concentration and an evident adrenal atrophy. Zona fasciculata, the main producer of glucocorticoids, was decreased in volume, due to a lowering in both the number and average volume of its parenchymal cells. Subcutaneous ACTH infusion (0.1 pmol.min-1), administered during the last week following hypophysectomy, restored the normal blood level of ACTH and completely reversed all effects of hypophysectomy on the adrenals. Subcutaneous infusion for one week with alpha-helical-CRH or corticotropin-inhibiting peptide (1 nmol.min-1), which are competitive inhibitors of CRH and ACTH, evoked a further significant lowering of plasma corticosterone concentration and markedly enhanced adrenal atrophy in hypophysectomized rats. These findings strongly suggest that an extrahypothalamic pituitary CRH/ACTH system may be involved in the maintenance of the growth and steroidogenic secretory activity of the rat adrenal cortex.

Adrenal Glands↗

PubMed1993

Effects of a calcium antagonist on the pituitary-adrenal axis.

It has been proposed that calcium is involved, as second messenger, in the regulation of various pituitary hormones including ACTH. Several evidences indicate that calcium-entry blockers agents (i.e. nifedipine) inhibit oCRH-dependent ACTH stimulation "in vitro". To further investigate these aspects we tested the effects of a calcium antagonist nitrendipine on basal and oCRH-stimulated ACTH secretion, in 6 hypertensive patients, with normal hypothalamus pituitary adrenal axis. Nitrendipine 20 mg per os once daily for 30 days, was efficacious in lowering blood pressure but did not modify ACTH and cortisol response to oCRH (200 micrograms i.v.), in spite of a minor inhibitory effect on the concomitant aldosterone response. These data indicate that ACTH secretion is not significantly modified by calcium antagonists, which can exert a detectable effect on adrenal zona glomerulosa.

Adrenocorticotropic Hormone↗

PubMed1992

The effects of ageing on the morphology and function of the zonae fasciculata and reticularis of the rat adrenal cortex.

The morphological counterpart of the well-known age-dependent marked impairment of glucocorticoid secretion of rat adrenals was investigated by use of morphometric techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Despite the notable lowering of both basal and ACTH-stimulated production of corticosterone by collagenase-dispersed inner adrenocortical cells, ACTH and corticosterone plasma concentrations displayed significant increases with ageing. Zona fasciculata (ZF) and zona reticularis (ZR) showed a notable hypertrophy in aged rats, which was due to rises in both the average volume and number of their parenchymal cells. The hypertrophy of ZF and ZR cells was in turn associated with increase in the volume of the mitochondrial compartment and proliferation of smooth endoplasmic reticulum, i.e., the two organelles involved in steroid-hormone synthesis. All these morphologic changes, conceivably due to the chronic exposure to high levels of circulating ACTH, are interpreted as a response enabling ZF and ZR to compensate for their age-dependent lowering in glucocorticoid secretion. Stereology also demonstrated that ZF and ZR cells underwent a striking age-related lipid-droplet repletion. Lipid droplets are the intracellular stores of cholesterol esters, the obligate precursors of steroid hormones in rats. This finding is in keeping with the contention that the mechanism underlying the age-dependent decline in rat-adrenal glucocorticoid secretion mainly involves impairments of the utilization of intracellular cholesterol previous to its intramitochondrial transformation to pregnenolone.

Adrenocorticotropic Hormone↗

PubMed1992

Age-related changes in the morphology and function of the zona glomerulosa of the rat adrenal cortex.

The age-related changes in the morphology and function of rat adrenal zona glomerulosa (ZG) were investigated by coupled stereological and radioimmunological techniques. For this purpose 4-, 8-, 16- and 24-month-old rats were studied. Aging caused a notable lowering in the plasma aldosterone concentration and a marked decrease in both basal and ACTH- or angiotensin II (ANG-II)-stimulated secretion of collagenase-dispersed ZG cells. Plasma renin activity (PRA) underwent an age-dependent decrease, while the plasma level of ACTH displayed a significant rise. ZG and its parenchymal cells did not evidence any age-related morphologically demonstrable alteration in their growth, nor ZG cells showed any marked ultrastructural change, with the exception of a severe lipid-droplet repletion. This last finding is in keeping with the aging-induced decrease in the secretory activity of ZG cells, inasmuch as lipid droplets are the intra-cellular stores of cholesterol esters, the obligate precursors of steroid hormones in rat adrenals. ACTH and ANG-II are well known to be involved in the maintenance of the growth of rat ZG; thus, the combined impairment of ANG-II production (as evidenced by PRA lowering) and increase in ACTH secretion may maintain unchanged ZG growth during aging.

Aging↗

PubMed1992

Usefulness of atrial natriuretic peptide assay in primary aldosteronism.

Atrial natriuretic peptide (ANP) can be elevated in conditions which are characterized by increased atrial pressure and or expanded plasma volume. We and others have previously shown a significant increase of ANP plasma levels in a small number of patients with primary aldosteronism. In this study we have extended the assay of plasma ANP to a larger number of patients. We studied ANP plasma levels before and after upright posture and acute sodium load in 16 patients with aldosteronoma (APA) and 13 with idiopathic aldosteronism (IHA). The study was repeated also after the removal of aldosteronoma. In patients with primary aldosteronism, the mean supine ANP plasma level was significantly higher than in the age matched normal subject group; supine ANP was significantly higher in the APA than in the IHA group. The decrease of ANP levels after upright posture was significant in both groups. The ANP increase after acute saline load was similar in APA and in IHA. After the removal of aldosteronoma ANP values returned to normal. In conclusion, it is confirmed that plasma ANP levels are elevated in primary aldosteronism and could reflect a greater volume expansion in patients with APA. Despite this difference, ANP still responds to physiological stimuli in both groups. Finally, ANP measurement can provide an additional tool in the differential diagnosis between APA and IHA.

Adenoma↗

PubMed1991

Hypertensive congenital adrenal enzymatic defects detected by high-performance liquid chromatography of corticosteroids.

The simultaneous measurement of the adrenal deoxycorticosterone (DOC), 18-OH-DOC, corticosterone (B), 18-OH-B, 11-deoxycortisol (S) and cortisol (F) present in human plasma in cases of adrenal dysfunction was accomplished using a high-performance liquid chromatographic (HPLC) system with a UV detector and with a radioimmunoassay (RIA). After a solid-phase extraction, plasma samples were separated by HPLC using a gradient of water-acetonitrile-ethanol on a radial compressed reversed-phase column. In a 70-min cycle, a complete separation of adrenal steroids was accomplished. The UV detector allowed direct measurement of F in each plasma sample while in selected cases B and S were directly determined. It was therefore possible quickly to identify patients with hypertensive congenital adrenal enzymatic defects with this method: the 17-alpha-hydroxylase deficiency characterized by the absence of measurable levels of F with an evident peak corresponding to B and the 11-beta-hydroxylase deficiency in which high levels of S without F are detected. The RIA of DOC, B, 18-OH-DOC and 18-OH-B complete the characterization of the adrenal defect. Therefore, with this HPLC method it is possible to recognize the major hypertensive adrenal enzymatic deficiencies such as the defect of 17-alpha-hydroxylase or 11-beta-hydroxylase. With "RIA" detectors an almost complete spectrum of adrenal steroid secretion can be obtained.

Adrenal Cortex Hormones↗

PubMed1991

Steroids and hypertension.

Primary aldosteronism is the principal disorder of zona glomerulosa and a number of subsets have been identified: unilateral adenoma; bilateral micro- or macro-nodular hyperplasia (idiopathic aldosteronism); primary hyperplasia and aldosterone-producing carcinoma either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable and our experience is presented in detail. Unfortunately the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role for adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. A qualitative biochemical abnormality in this disorder consists of marked over-production of products of the cortisol C18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with three affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids [deoxycorticosterone (DOC), corticosterone and their 18-hydroxy compounds] are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia (CAH), the 11 beta-hydroxylase (11-OHDS) and the 17 alpha-hydroxylase deficiency syndromes (17-OHDS), which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-OHDS, while all ACTH-dependent MCH are very high in the 17-OHDS. The molecular basis of gene abnormalities of this disorder are currently under investigation, and preliminary data obtained in some of our patients are presented. Finally a syndrome of apparent mineralocorticoid excess, which is not a primary disorder of the adrenal cortex, describes the association of an unexplained hypermineralocorticoid state with a decreased rate of peripheral 11 beta-hydroxy dehydrogenation of cortisol to cortisone. Studies on this syndrome have led to the hypothesis that peripheral cortisol inactivation is the normal mechanism permitting specific mineralocorticoid recognition. The syndrome exists in two forms both characterized by a decreased turnover of a normal level of plasma cortisol, but in the type I variant an elevated cortisol/cortisone metabolite ratio is found, whereas in the type II variant this ratio is normal. Three patients of the latter form have recently been described by us and are shortly illustrated.(ABSTRACT TRUNCATED AT 400 WORDS)

Cushing Syndrome↗

PubMed1990

Atrial natriuretic peptide in Cushing's disease.

Atrial Natriuretic Peptide (ANF), is secreted by atrial myocytes in response to atrial stretch. Its plasma levels have been found elevated in conditions leading to salt and fluid repletion and consequent atrial distention. Recently, it has been demonstrated that dexamethasone can enhance ANF secretion, by acting on ANF gene expression and mRNA synthesis. High plasma levels of ANF have been observed in normal man after administration of cortisol and ACTH. In the case of glucocorticoid excess, as in Cushing's disease, limited and conflicting data are available. Therefore, we measured ANF basal values and ANF response to postural changes and volume expansion in eight patients with Cushing's disease. In our patients ANF values were higher than normals. ANF responded to volume expansion, 47.8 +/- 5.1 pg/ml before sodium load and 69.9 +/- 7.0 pg/ml after sodium load, and changed minimally after postural manoeuvres, 47.3 +/- 3.2 pg/ml supine and 41.7 +/- 5.1 pg/ml upright. These data indicate that ANF secretion is enhanced in Cushing's disease, and its regulation is partially altered. Since in this condition hypervolemia has not been certainly demonstrated, a direct relationship between elevated ANF and glucocorticoid excess could be suggested.

Adult↗

PubMed1990

Atrial natriuretic peptide infusion in primary aldosteronism. Renal, hemodynamic and hormonal effects.

We have previously shown that a bolus injection of alpha-human atrial natriuretic peptide (alpha-h-ANP) (100 micrograms) in patients with primary aldosteronism induces a transient decrease of blood pressure and a marked natriuresis, but no changes in plasma aldosterone levels. Eight additional cases were studied with a different protocol. Alpha-h-ANP was infused at the dose of 50 ng/kg/min over 1 h, after a bolus of 50 micrograms; saline alone was infused as control. Blood pressure, heart rate, plasma aldosterone, plasma renin activity, cortisol, serum and urinary Na and K and urinary volume were measured. A slight fall in blood pressure, without heart rate changes, was obtained within the first 5 min; this lasted throughout the infusion and for 1 h afterwards. Urinary volume and urinary sodium were significantly higher than controls during the first 2 h, while urinary potassium slightly increased only during the first hour. Plasma renin activity remained suppressed. Plasma aldosterone levels were similar throughout the infusion. Cortisol was not significantly different than placebo except that there was a significant rise after stopping ANP. These data confirm the potent natriuretic effect of ANP infusion and the lack of correlation between ANP induced natriuresis and the effect of ANP on aldosterone in patients with primary aldosteronism.

Adult↗

PubMed1990

New aspects of mineralocorticoid hypertension.

Primary aldosteronism is the principal disorder of the zona glomerulosa, and a number of subsets have been identified: unilateral adenoma, bilateral micro- or macronodular hyperplasia (idiopathic aldosteronism), primary hyperplasia, and aldosterone-producing carcinoma, either adrenal or ectopic. The diagnostic criteria for a correct differential diagnosis of these subsets are now quite reliable, and our experience is presented in detail. Unfortunately, the pathogenesis of most of these forms is still poorly recognized and requires further investigation. An extreme sensitivity to angiotensin II is present in patients with idiopathic aldosteronism, and a role of adrenal renin is now being advocated. A peculiar form of hyperaldosteronism is the glucocorticoid-remediable subtype. An unusual sensitivity of aldosterone to ACTH is present in this form. The qualitative biochemical abnormality in this disorder consists of a marked overproduction of products of the cortisol C-18-oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, which are more abundant than aldosterone and 18-hydroxycorticosterone. A family with 3 affected sibs has been studied by our group. In other clinical situations, classical zona fasciculata mineralocorticoids (deoxycorticosterone [DOC], corticosterone, and their 18-hydroxy compounds) are secreted in excess. The hypertensive diseases of this zone are rare DOC-secreting tumors and two forms of congenital adrenal hyperplasia, the 11 beta-hydroxylase and 17 alpha-hydroxylase deficiency syndromes, which are identified by the presence of hypokalemia and suppressed renin activity. DOC is the only mineralocorticoid hormone (MCH) oversecreted in the 11-hydroxylase deficiency syndromes, while all ACTH-dependent MCH levels are very high in the 17-hydroxylase deficiency syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗

PubMed1990

Role of protein kinase C on the steroidogenic effect of angiotensin II in the rat adrenal glomerulosa cell.

The role of protein kinase C (PKC) in the steroidogenic action of angiotensin II (AII) was investigated by depletion of endogenous PKC using prolonged incubation with phorbol ester and direct measurement of PKC in isolated rat adrenal glomerulosa cells. PKC activity was measured by incorporation of 32P from [gamma 32P]ATP into histone in the presence of cytosolic and detergent-solubilized membrane fractions purified by diethylaminoethyl cellulose chromatography. Basal PKC activity was higher in cytosol than in membranes (1,000 +/- 57 and 413 +/- 14 pmol P incorporated/mg.min, respectively). After incubation of the cells with AII for 5, 15, 30, and 60 min, PKC activity in the cytosol decreased by 5, 18, 25, and 27%, respectively, while in the membrane there was a transient increase of 15% at 15 min returning to basal by 60 min. Incubation of the cells with 100 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in transient translocation of PKC activity to the membrane (15 min) which was followed by a 64% decrease in total cellular enzyme activity after 3 h. In PKC-depleted cells, the aldosterone response to ACTH was increased by 25% but AII-stimulated steroidogenesis was unchanged. In contrast, in cells in which PKC was translocated to the membrane by a 15 min preincubation with TPA, aldosterone response to AII was enhanced by 40%, while the response to ACTH was reduced by 30%; under these conditions membrane PKC levels rapidly returned to basal. However, the changes in aldosterone response were still evident when addition of AII or ACTH was delayed for up to 30 min after removal of TPA, indicating a persistent modification in the cell membrane secondary to PKC activation. Aldosterone responses to potassium were not altered by preincubation of the cells with TPA. The inactive phorbol ester analog, 4 alpha-hydroxyphorbol-12,13-dibutyrate, had no effect on the steroid responses to either stimulus. The small but significant translocation of PKC activity from cytosol to membrane after treatment of rat adrenal glomerulosa cells with AII suggests that AII activates PKC. However, the fact that aldosterone responses to AII are potentiated during TPA-induced PKC translocation to the membrane suggests that AII and phorbol esters do not share the same mechanism of action in the regulation of steroidogenesis.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗