Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adrenocortical causes of hypertension are established by examining the mineralocorticoid hormones produced in the zona glomerulosa and zona fasciculata. In the zona glomerulosa, aldosterone excess leads to hypertension, hypokalemia, and suppressed plasma renin activity, with increased concentrations of urinary aldosterone (either as the 18-glucuronide or free aldosterone) as an index of its production. Identifying a tumor by computed tomography scan verifies the diagnosis of a correctable lesion. If no tumor is found, several maneuvers are used to identify primary adrenal hyperplasia, a disorder with autonomous aldosterone production, for which reduction of adrenal mass is curative. The zona fasciculata has two major pathways: the 17-deoxy pathway, where deoxycorticosterone (DOC) and corticosterone are the significant steroids, and the 17-hydroxy pathway, which leads to cortisol production. Tumors of the 17-deoxy pathway, DOC-producing adenomas, have increased concentrations of DOC and its precursor steroids, normal concentrations of cortisol, and suppression of aldosterone production secondary to suppression of the renin system. Two enzymatic defects in the zona fasciculata, 11 beta- and 17 alpha-hydroxylase deficiency, can be first readily identified by the virilization in the former, hypogonadal features in the latter. Steroid patterns are diagnostic. DOC is produced in excess in both deficiencies and is the cause of the hypertension. Deficient or impaired 11 beta-hydroxy steroid dehydrogenase in the apparent mineralocorticoid excess syndrome or after licorice ingestion retards the conversion of cortisol to inactive cortisone in the kidney, leading to mineralocorticoid hypertension; this leads to suppression of the renin system and subsequently of aldosterone.
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PMID:Steroid characteristics of mineralocorticoid adrenocortical hypertension. 191

Primary aldosteronism is classified as aldosterone-producing adenoma (APA), idiopathic hyperaldosteronism (IHA), unilateral adrenal hyperplasia (UAH), primary adrenal hyperplasia (PAH), adrenal cancer, and glucocorticoid-remediable aldosteronism. We describe here 4 cases of primary aldosteronism due to unilateral hyperaldosteronemia, demonstrating unique histopathologic findings, such as unilateral multiple adrenocortical micronodules in the affected adrenals. Thirty-three patients with primary aldosteronism were consecutively admitted; 27 of them were treated by unilateral adrenalectomy. Four of them also had unilateral adrenal hypersecretion of aldosterone by selective adrenal venous sampling and adrenocortical multiple micronodules without an adenoma. These patients had hyporeninemic hyperaldosteronism with normokalemic hypertension. In these patients, furosemide plus upright test failed to increase plasma renin activity (PRA); the ratio of plasma aldosterone concentration (PAC) to PRA at 90 minutes after captopril administration was similar to that in patients with IHA and APA. Aldosterone concentrations were increased in each unilateral adrenal vein, and poorly encapsulated multiple adrenocortical micronodules from 2 to 3 mm in diameter were microscopically detected in the resected adrenal glands. Immunohistochemical analysis of steroidogenic enzymes, including cholesterol side chain cleavage, 3beta-hydroxysteroid dehydrogenase, 21-hydroxylase, 17alpha-hydroxylase, and 11beta-hydroxylase, indicated that the cortical cells within these micronodules were active in aldosterone production, while the non-nodular zona glomerulosa cells were inactive. We conclude that the clinical and pathologic characteristics of our 4 cases with unilateral multiple adrenocortical micronodules (UMN) are distinct from those of APA, IHA, UAH, and PAH. Furthermore, unilateral hyperaldosteronemia induced by UMN may be frequently misdiagnosed, because standard imaging tests, which cannot always detect tiny abnormalities of adrenals, showed "normal adrenal glands" in these patients. Thus, primary aldosteronism due to UMN should be carefully examined for differential diagnosis of each form of hyperaldosteronemia.
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PMID:Unique cases of unilateral hyperaldosteronemia due to multiple adrenocortical micronodules, which can only be detected by selective adrenal venous sampling. 1188 72

During testicular development, fetal and adult populations of Leydig cells arise sequentially. Previous studies have shown that androgen action is required for normal steroidogenic activity in the mouse testis. Therefore, to determine the role of androgens in regulating fetal and adult Leydig cell differentiation and function, Leydig development has been measured in mice lacking functional androgen receptors (AR-null). The Leydig cell number was normal on day 5 after birth in AR-null mice but failed to increase normally thereafter and was about 30% of the control level on day 20 and about 60% of control level in adult animals. Levels of 15 different mRNA species expressed specifically in Leydig cells were measured by real-time PCR in AR-null and control animals. Expression levels of all mRNA species were normal on day 5 when only fetal Leydig cells are present. In older animals, which contain predominantly adult Leydig cells, five of the mRNA species (3beta-hydroxysteroid dehydrogenase (3betaHSD) type 1, cytochrome P450scc, renin, StAR protein and luteinising hormone receptor) were expressed at normal or increased levels in AR-null mice. All other mRNA species measured showed significantly reduced expression in older animals, and three of these mRNA species (17beta-hydroxysteroid dehydrogenase type III, prostaglandin D (PGD)-synthetase and 3betaHSD type VI), which are only expressed in the adult population of Leydig cells, were barely detectable in the adult AR-null mouse. The results show that in the absence of androgen receptors, fetal Leydig cell function is normal, but there is a developmental failure of adult Leydig cell maturation, with cells only aquiring partial characteristics of the adult population.
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PMID:Failure of normal adult Leydig cell development in androgen-receptor-deficient mice. 1215 79

Systemic aldosterone plays an important role in the development of the microvascular disease and glomerular damage of the kidney in patients with diabetes mellitus and hyperlipidemia. Here, we investigated the possibility of local production of aldosterone in the kidney, using human primary glomerular mesangial cells. These cells produced both pregnenolone and aldosterone measured by specific radioimmunoassay and/or gas chromatography/mass spectrometry (GC/MS) methods. The production of both steroids was significantly stimulated by treatment with LDL, while angiotensin II had a synergistic effect. Adrenocorticotropic hormone (ACTH) and (Bu)2cAMP, on the other hand, failed to stimulate aldosterone production by these cells, suggesting that the local production of this steroid by mesangial cells is regulated differently from that of adrenal zona glomerulosa cells. Mesangial cells expressed the mRNA of the LDL receptor and steroidogenic enzymes, such as P450scc, 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 21-hydroxylase and CYP11B2. Mesangial cells also expressed mRNA of the mineralocorticoid receptor (MR), and LDL stimulated its abundance by three-fold, while spironolactone, a completive antagonist of aldosterone, completely abolished this LDL effect. Since MR is a known mineralocorticoid-responsive gene as well as an intracellular receptor molecule for this steroid, these results suggest that locally produced aldosterone is biologically active, stimulating the transcription rates of the mineralocorticoid-responsive genes by activating the MR in mesangial cells. These pieces of evidence indicate that human mesangial cells are an aldosterone-producing tissue in which LDL plays a major regulatory role. Therefore, human renal mesangial endocrine system may contribute to local aldosterone concentrations and effects in the renal glomerulus independently of the systemic renin--angiotensin--aldosterone system and may participate in the development and progression of glomerular damage in several pathologic conditions.
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PMID:Human renal mesangial cells produce aldosterone in response to low-density lipoprotein (LDL). 1599 78

A 46-year-old male with long-term treatment-resistant hypertension and past history of cerebral hemorrhage was found to have suppressed plasma renin activity (PRA) and normal plasma aldosterone concentration (PAC) with aldosterone/renin ratio of 25.3. Furosemide plus upright test did not stimulate PRA, but computed tomography scan of the abdomen revealed no abnormal lesions in either adrenal gland. Selective adrenal venous sampling (SAVS) showed that PAC in the left and the right adrenal vein were 1000 ng/dl and 230 ng/dl, respectively, which increased to 1500 ng/dl and 620 ng/dl, respectively, after ACTH stimulation. Diagnosis of primary aldosteronism due to hypersecretion of aldosterone from the left adrenal gland was made, and laparoscopic left adrenalectomy was performed. Pathological examination of the 'apparently normal' adrenal tissue resected revealed the presence of poorly encapsulated multiple adrenocortical micronodules which showed positive immunoreactivity for 3beta-hydroxysteroid dehydrogenase by immunohistochemical study, but negative immunoreactivity in the hyperplastic zona glomerulosa consistent with paradoxical hyperplasia associated with primary aldosteronism. Postoperatively, PRA was normalized and his high blood pressure was well controlled with lower doses of antihypertensive drugs than those used before surgery. The clinicopathological features of our case are consistent with the diagnosis of unilateral multiple adrenocortical micronodules (UMN), a new subset of primary aldosteronism, in which SAVS proved to be a useful diagnostic tool for its localization.
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PMID:A case with primary aldosteronism due to unilateral multiple adrenocortical micronodules. 1612 11

The case of a patient with primary aldosteronism due to unilateral adrenal hyperplasia (UAH) is reported. A 43-year-old man with an 8-year history of hypertension presented at our institution with hypokalemia, increased plasma aldosterone concentration (PAC), and suppressed plasma renin activity (PRA). An abdominal CT scan showed almost normal adrenal glands with slight enlargement in the left gland. 131I-Norcholesterol adrenal scintigraphy under dexamethasone suppression showed bilaterally decreased uptake. To rule out idiopathic hyperaldosteronism, an adrenal vein sampling before and after ACTH stimulation was performed and a left-sided lateralization of PAC was observed. A left adrenalectomy was performed, and the patient had a good clinical and biochemical response. Micronodular hyperplasia was discovered in the adrenal gland histologically, and in the immunohistochemical analysis, positive staining for 3beta-hydroxysteroid dehydrogenase in micronodular lesions confirmed the diagnosis of UAH. Although UAH is a rare subset of primary aldosteronism, it is surgically correctable as a unilateral autonomous aldosterone-producing lesion. Careful investigations, including bilateral adrenal vein sampling, should be performed for the diagnosis.
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PMID:A case of primary aldosteronism due to unilateral adrenal hyperplasia. 1613 69

We demonstrated a rare case of bilateral aldosteronoma accompanied by secondary aldosteronism in a 37-year-old man with chronic renal failure on hemodialysis. He initially developed immunoglobulin A nephropathy at 11 years old, and had been treated with hemodialysis since the age of 17 years. His blood pressure was 110/68 mmHg, and no other abnormal findings were detected. Laboratory findings revealed that serum potassium was 3.9 mmol/L; plasma renin activity, 4.8 ng/ml/h and plasma aldosterone, 19,000 pg/mL. Abdominal computed tomography revealed bilateral adrenocortical tumors, measuring 34 and 40 mm in diameter in right and left tumors, respectively. (131)I-Adosterol scintigram showed bilateral accumulation. Left adrenalectomy was performed under laparoscopy. The tumor was encapsulated and well-circumscribed. The majority of the tumor was composed of a dark-brown portion admixed with sporadic foci of golden-yellow portions. Hyaline degeneration was detected in its central portion. The tumor was composed of clear cortical cells in viable portions. Tumor cells demonstrated immunoreactivity for the cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase (3beta-HSD II) and 21-hydroxylase, but not 17 alpha-hydroxylase. In the adjacent non-neoplastic adrenals, 3 beta-HSD II was markedly present in the hyperplastic glomerulosa zone. These findings suggest that the presence of secondary aldosteronism, which is closely related to the conditions of chronic renal failure on hemodialysis, eventually promoted the development of bilateral aldosteronoma from the zona glomerulosa hyperplasia.
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PMID:Bilateral aldosteronoma associated with secondary aldosteronism in a chronic hemodialysis subject. 2051 19