Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

These studies investigated whether treatment with carbenoxolone (CBX), an inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), resulted in an enhanced mineralocorticoid response to endogenous or infused cortisol. In conscious sodium replete sheep with a parotid fistula, infusion of CBX (40 mg/h for 10 days) did not increase mean arterial pressure, or change sodium and potassium status or plasma renin concentration, but significantly increased the half-life of 1,2[3H] cortisol from 18.6 +/- 4.0 to 38.8 +/- 3.9 min (p < 0.05) and reduced the blood clearance rate of cortisol (BCR) from 31 +/- 3 to 15 +/- 4 L/h (p < 0.01). The reduction in cortisol BCR was associated with reduction in cortisol secretion rate from 433 +/- 116 to 181 +/- 79 nmol/h (p < 0.01). Cortisol (8 mg/h) for 5 days increased mean arterial pressure (from 83 +/- 2 to 101 +/- 5 mmHg, p < 0.001) and caused natriuresis, hypokalaemia and hyperglycaemia. These responses were unaltered when cortisol was infused from the fifth to the tenth day of CBX infusion. These findings suggest that in sheep, carbenoxolone is either a less potent inhibitor of 11 beta-HSD2 than in other species or 11 beta-HSD2 may not be the only mechanism, which determines the specificity of the MR.
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PMID:Carbenoxolone does not cause a syndrome of mineralocorticoid excess in sheep. 951 20

The aim of this study was to assess the relative influence on the 24-h aldosterone profile of the adrenocorticotropic system, primarily modulated by a circadian rhythmicity, and the renin-angiotensin system, which is influenced by sleep. Cortisol, plasma renin activity (PRA), and aldosterone were measured for 24 h in healthy subjects under basal conditions, once with nocturnal sleep and once with a night of sleep deprivation followed by 8 h of daytime sleep. The sleep period displayed high mean aldosterone levels, pulse amplitude, and frequency that were reduced during waking periods. During sleep, aldosterone pulses were mainly related to PRA oscillations, whereas they were mainly associated with cortisol pulses during waking periods. Cross-correlation analysis between sleep electroencephalographic activity in the delta band and aldosterone levels yielded significant results, aldosterone following delta waves by approximately 30 min. This study demonstrates that the 24-h aldosterone profile is strongly influenced by sleep processes. A dual influence, by the renin-angiotensin system during sleep and by the adrenocorticotropic system during wakefulness, is exerted on aldosterone pulses throughout the 24-h period.
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PMID:Aldosterone release during the sleep-wake cycle in humans. 988 49

To study a generalized stress reaction as well as endothelin-1 concentrations during moderate hyperbaria and hyperbaric oxygen (HBO2), eight professional divers were exposed to air (O2 21%, AIR) and oxygen (O2 100%, HBO2) at 2.5 atm abs for 60 min in separate sessions. Plasma concentrations of epinephrine, norepinephrine, dihydroxyphenylglycol (metabolite of norepinephrine), cortisol, ADH, renin, aldosterone, pro-ANP, and endothelin-1 were analyzed before, during, and 20 min after the treatments. Endothelin-1 increased significantly (6% during HBO2 and 18% during AIR, and 30 and 34% after the treatments, respectively, P = 0.032). There was no statistically significant difference in the changes of mean norepinephrine and dihydroxyphenylglycol levels between the treatments, although both seemed to change slightly during the treatments, but not over the baseline (time effect P = 0.031 and P = 0.011, respectively). Cortisol levels decreased significantly (P = 0.001) during the treatments. No significant changes were found in other analyzed hormones. The authors concluded that a) HBO2, and hyperbaric air at 2.5 atm abs do not induce a generalized hormonal stress reaction, and b) endothelin-1 increases during HBO2 and hyperbaric air at 2.5 atm abs.
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PMID:Effect of hyperbaric conditions on plasma stress hormone levels and endothelin-1. 1037 27

Blacks appear, on average, to retain more Na than whites. A higher production rate of mineralocorticoids could explain the greater Na retention in blacks. Although production of aldosterone has been shown to be lower in blacks, the level of another mineralocorticoid may be increased. Plasma levels of deoxycorticosterone and cortisol were measured in young whites (n=23; age=16.4+/-3.1[SD] years) and young blacks (n=25; age=13.8+/-1.3 years). Blacks had lower plasma levels of renin activity and aldosterone and lower urinary aldosterone excretion rates; thus, they appeared to be representative of blacks that retain additional Na. Plasma deoxycorticosterone levels were lower in blacks than in whites both at baseline (247+/-161 versus 381+/-270 pmol/L, P=0.048) and after stimulation with adrenocorticotropic hormone (822+/-294 versus 1127+/-628 pmol/L at 30 minutes, P=0.047; 925+/-366 versus 1440+/-834 pmol/L at 60 minutes, P=0.013). Cortisol levels were also lower in blacks at baseline (P=0.014) but were not significantly different from levels in whites after stimulation with adrenocorticotropic hormone. In a larger cohort of 407 whites (age=12.0+/-2.9 years) and 247 blacks (age=12.9+/-3.1 years), 18-hydroxycortisol excretion rates were also lower in blacks (P=0. 021). In conclusion, increased Na retention in blacks does not appear to be secondary to increased production of either aldosterone, deoxycorticosterone, cortisol, or 18-hydroxycortisol. A primary renal mechanism may mediate the increase in Na reabsorption in blacks.
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PMID:Levels of mineralocorticoids in whites and blacks. 1045 60

To differentiate between the effect of cold and hydrostatic pressure on hormone and cardiovascular functions of man, a group of young men was examined during 1-h head-out immersions in water of different temperatures (32 degrees C, 20 degrees C and 14 degrees C). Immersion in water at 32 degrees C did not change rectal temperature and metabolic rate, but lowered heart rate (by 15%) and systolic and diastolic blood pressures (by 11 %, or 12%, respectively), compared to controls at ambient air temperature. Plasma renin activity, plasma cortisol and aldosterone concentrations were also lowered (by 46%, 34%, and 17%, respectively), while diuresis was increased by 107%. Immersion at 20 degrees C induced a similar decrease in plasma renin activity, heart rate and systolic and diastolic blood pressures as immersion at thermoneutrality, in spite of lowered rectal temperature and an increased metabolic rate by 93%. Plasma cortisol concentrations tended to decrease, while plasma aldosterone concentration was unchanged. Diuresis was increased by 89%. No significant differences in changes in diuresis, plasma renin activity and aldosterone concentration compared to subjects immersed to 32 degrees C were observed. Cold water immersion (14 degrees C) lowered rectal temperature and increased metabolic rate (by 350%), heart rate and systolic and diastolic blood pressure (by 5%, 7%, and 8%, respectively). Plasma noradrenaline and dopamine concentrations were increased by 530% and by 250% respectively, while diuresis increased by 163% (more than at 32 degrees C). Plasma aldosterone concentrations increased by 23%. Plasma renin activity was reduced as during immersion in water at the highest temperature. Cortisol concentrations tended to decrease. Plasma adrenaline concentrations remained unchanged. Changes in plasma renin activity were not related to changes in aldosterone concentrations. Immersion in water of different temperatures did not increase blood concentrations of cortisol. There was no correlation between changes in rectal temperature and changes in hormone production. Our data supported the hypothesis that physiological changes induced by water immersion are mediated by humoral control mechanisms, while responses induced by cold are mainly due to increased activity of the sympathetic nervous system.
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PMID:Human physiological responses to immersion into water of different temperatures. 1075 Nov 6

The renin angiotensin system is important in the regulation of fetal blood pressure. This study investigated the expression of angiotensin AT(1) and AT(2) receptors in the ovine fetal heart, aorta and umbilical artery, and how these receptors are affected by cortisol. Cortisol infusion into the fetus has previously been shown to cause an increase in fetal blood pressure. We hypothesised that this effect of cortisol is mediated by upregulation of the angiotensin AT(1) receptor. Binding studies performed on tissues with intact endothelium demonstrated both receptor subtypes in the fetal aorta and right ventricle, although the latter contained mainly angiotensin AT(2) receptors. In contrast, only angiotensin AT(1) receptors were found in the umbilical artery. Cortisol infusion into fetuses (3 mg/day for 3-5 days) caused a physiological increase in plasma cortisol levels to 29+/-4 nM. This was associated with an increase in systolic pressure (57.8+/-1.7 vs. 52.2+/-1.5 mm Hg, P<0.05), but cortisol had no effect on the density or affinity of angiotensin receptors, nor on the in vitro contractile responses of carotid and umbilical arterial rings to 5-microM angiotensin II. In conclusion, this study has demonstrated differential expression of angiotensin AT(1) and AT(2) receptors in the different regions of the ovine fetal cardiovascular system and that the angiotensin AT(1) receptor is functional. The lack of any effect of low doses of cortisol on these receptors and on the contractility of isolated fetal vessels to angiotensin II suggests cortisol acts by other mechanisms to raise fetal arterial pressure.
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PMID:Effect of cortisol on fetal ovine vascular angiotensin II receptors and contractility. 1104 Mar 51

Nitrites and nitrates are consumed nonchalantly in diet. Organic nitrates are also used as vasodilators in angina pectoris, but the therapy is associated with tolerance whose mechanism remains elusive. Previously, we found inorganic nitrate inhibited steroidogenesis in vitro. Because adrenocorticoids regulate water and electrolyte metabolism, tolerance may ensue from steroid deficiency. We have studied the effects of nitrite and nitrate on in vitro synthesis and in vivo blood levels of steroid hormones. In vitro, nitrite was more potent than nitrate in inhibiting human chorionic gonadotropin (hCG)-stimulated androgen synthesis by Mouse Leydig Tumor cells. At concentrations above 42 mM, nitrite completely inhibited androgen synthesis, and, unlike nitrate, the inhibition was irreversible by increasing hCG concentration. The cAMP production remained intact but reduced with both ions. The nitric oxide (NO) scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (c-PTIO) significantly increased hCG- or cAMP-stimulated androgen synthesis in all buffers, suggesting that NO is a chemical species directly involved in the nitrite/nitrate-induced inhibition. This is further supported by c-PTIO countering the inhibitory action of methylene blue on androgen synthesis. Rats given distilled water containing 50 mg/L NaNO(2) or NaNO(3) for 4 weeks drank significantly less daily. At the end, their blood corticosterone and testosterone levels were significantly decreased. The adrenocortical histology showed bigger lipid droplets, which are pathogonomic of impaired steroidogenesis. Nitrite and nitrate are metabolized to NO, which binds heme in cytochrome P450 enzymes, thereby inhibiting steroidogenesis. Therapeutic nitrates likewise may decrease adrenal (and gonadal) steroidogenesis. Cortisol deficiency would impair water excretion causing volume expansion, and aldosterone deficiency would cause sodium loss and raised renin. Paradoxically, volume expansion without sodium retention and raised renin has all been reported in tolerance.
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PMID:Decreased steroid hormone synthesis from inorganic nitrite and nitrate: studies in vitro and in vivo. 1113 44

The adrenal glands are a major source of steroid hormone biosynthesis. In normal physiology, the pituitary hormone corticotropin (ACTH) regulates the secretion of glucocorticoids via its G protein-coupled receptor (ACTHR), the product of the MC2R gene. Aldosterone is another major product of the adrenal gland; its regulation is controlled mainly by the renin-angiotensin system, although ACTH plays a role, too, especially under certain pathological conditions. The adrenal gland also secretes lesser amounts of androgens and intermediate metabolites of all these steroids. Unregulated secretion of any of these hormones can be caused by tumors, adrenocortical adenomas or carcinomas, and/or bilateral (or, rarely, unilateral) hyperplasia. Cortisol-producing hyperplasia of the adrenal glands is caused by two distinct syndromes, both of which have been directly or indirectly associated with protein kinase A signaling: (i) primary pigmented nodular adrenocortical disease (PPNAD) (a micronodular form of bilateral adrenal hyperplasia), either isolated (rarely) or in the context of Carney complex, is caused (in most cases) by mutations of the PRKAR1A gene; and (ii) ACTH-independent macronodular adrenal hyperplasia (AIMAH), or massive macronodular adrenal disease (MMAD), has been associated with aberrant (ectopic) expression, and presumably regulation, of various G protein-coupled receptors. AIMAH is a rare, sporadic condition affecting predominantly middle-aged men and women with an almost equal ratio (the latter in contrast to other forms of endogenous Cushing's syndrome). Some familial cases of AIMAH have also been described, and it appears that the pathophysiological phenomena underlying AIMAH may be present in the far more common, sporadic adrenocortical tumors and, perhaps, in the nodular growth detected in the adrenal glands of the elderly in the general population. Thus, the study of ectopic receptor expression and cAMP-dependent PKA activity in AIMAH may have wider implications for adrenal and, indeed, endocrine tumorigenesis.
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PMID:Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease. 1211 80

The Dex/CRH test is one of the most reliable neuroendocrine function tests for hypothalamic-pituitary-adrenocortical (HPA) system dysregulation in depression. Persistent overdrive of HPA system activity after successful antidepressant treatment predicts an enhanced risk for relapse of a depressive episode. As the renin-angiotensin system has been shown to play a role in HPA system activity, we investigated the impact of the angiotensin converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism, which determines ACE plasma concentrations, on HPA system dysregulation. We performed repeated combined Dex/CRH tests in 115 patients suffering from major depression. Dex/CRH test results were related to the I/D polymorphism within the ACE gene, which was assessed by PCR. Genotype frequencies were comparable to those in the general population (I/I 16.8%, I/D 59.3%, D/D 23.9%). D/D genotypes showed a higher cortisol stimulation during the first Dex/CRH test after admission than homozygous I-allele carriers (repeated measurement ANOVA: P=0.034). Cortisol area under the curve values were highest in those with the D/D genotype (mean+/-SEM [nmol/l*75 min]: 12700+/-2220), intermediate in those with the I/D genotype (9570+/-1000), and lowest in those with the I/I genotype (5160+/-1000; ANOVA: P=0.04). After successful antidepressive treatment and attenuation of HPA system overdrive these differences were no more detectable. The HPA axis stimulating properties of higher ACE and consecutively higher AT-II and/or lower substance P concentrations may be crucial factors for the HPA system hyperactivity during major depressive episodes.
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PMID:Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. 1214 30

The management of children and adolescents with congenital adrenal hyperplasia (CAH) remains difficult. To assess the current European practice in diagnosis and management of CAH, an ESPE (European Society for Paediatric Endocrinology) survey was circulated in 2000/2001. The questionnaire was answered by 34% of ESPE members, representing 125 institutions which cared for 6,553 CAH patients. Paediatric endocrinologists, surgeons, gynaecologists, geneticists, and psychologists are involved in the immediate care of the CAH neonate and his family. 44% of centres take part in neonatal screening programmes. In families at risk, prenatal dexamethasone therapy is started at a median gestational age of 6 weeks in a median dose of 20 microg/kg/day. 53% reported maternal adverse events, 8% observed adverse fetal events. Regarding feminizing surgery, 33% reported simultaneous clitoric reduction and vaginoplasty during infancy. However, clitoridectomy is still reported by 13% of centres, and vaginal dilatations have been performed by 27%. Although 71% of female CAH patients with psychosexual problems, only 17% undertake routine psychodiagnostics and counselling. Hydrocortisone is the substance used for the treatment of CAH during growth in 84%; the median dose (mg/m(2)/day) is 17.5 in infants, 15 in children and adolescents, and 13.75 in adults. The glucocorticoid dose is increased two- to sixfold during intercurrent stress. Mineralocorticoid is administered in cases of clinically manifest salt wasting and of elevated plasma renin activity, to decrease high glucocorticoid doses, or according to genotype. All participating ESPE members feel the need for further improvement in prenatal diagnosis and treatment, compliance during puberty, screening programmes, psychological aspects, and corrective surgery.
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PMID:Management of congenital adrenal hyperplasia: results of the ESPE questionnaire. 1232 19


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