Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arginine vasopressin (AVP) is released in response to changes in blood osmolality and is also a putative secretagogue for ACTH. However, it is unclear whether osmotically generated increases in AVP in the physiological range influence ACTH secretion. We have studied this question using our unique noninvasive technique for collecting pituitary venous blood in six normal conscious horses that received an iv infusion of hypertonic saline (HS; 5%, 0.07 ml/kg.min) for 45-60 min. Pituitary and jugular venous samples were collected every 5 min for 40 min before, during, and for 20 min after HS. During HS, mean blood osmolality rose (P less than 0.01), with a mean peak increase of 14.8 mosmol/kg (range, +6-+37 mosmol/kg). Jugular AVP rose (P less than 0.01) from 0.56 +/- 0.18 pmol/liter (mean +/- SEM) before HS to 2.16 +/- 0.86 pmol/liter during HS. Mean jugular AVP and osmolality were correlated (r = 0.82; P less than 0.05) during HS. Mean jugular ACTH concentrations increased (P less than 0.01) from 49 +/- 9 ng/liter before HS to 148 +/- 54 ng/liter during HS, while mean cortisol levels during and after HS exceeded basal levels (P less than 0.05). Pituitary AVP and ACTH concentrations exceeded jugular concentrations by up to 100-fold, and mean (P less than 0.01 for both) and peak (P less than 0.001 for both) levels increased during HS. AVP and ACTH secretion during HS were pulsatile. The mean and peak changes in pituitary AVP were significantly correlated with those in ACTH. For the six horses together, pituitary ACTH and AVP concentration changes occurred synchronously during the experiment (P less than 0.001), and the paired AVP and ACTH concentrations were highly correlated (r = 0.73; n = 129 pairs; P less than 0.001). We conclude that 1) physiological changes in AVP secretion are closely associated with comparable changes in ACTH secretion, and 2) osmotic signals that presumably activate the magnocellular neurons of the supraoptic and paraventricular nuclei may be physiologically relevant regulators of corticotrope function.
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PMID:Effect of an osmotic stimulus on the secretion of arginine vasopressin and adrenocorticotropin in the horse. 254 9

The effects of Ketoconazole (600 mg/day) were evaluated in 10 patients with Cushing's syndrome during a mean period of 4.5 weeks (range 1-12). The urinary free cortisol excretion (UFC) decreased by 21 +/- 15% (mean +/- SEM) (p less than 0.01) on day 1; 54 +/- 8% (p less than 0.0001) on day 2; 60 +/- 15% (p less than 0.0001) on day 3 and 87 +/- 3% (p less than 0.0001) on day 8 compared to baseline. Salivary cortisol at 0800 h decreased similarly. On day 3, 7 patients showed normal UFC values and on day 8, only 1 patient, with the ectopic ACTH syndrome, had persistent hypercortisolism. The cortisol decrease was associated with an increase in desoxycorticosterone values (p less than 0.01) and a decrease in dehydroepiandrosterone sulfate (p less than 0.001), delta 4 androstenedione (p less than 0.05) and testosterone (p less than 0.05). No significant variations were observed in ACTH, 11 desoxycortisol, aldosterone, plasma renin activity, corticosteroid-binding globulin and sex hormone-binding globulin. Side effects were few: mild clinical adrenal insufficiency (n = 5), oedema (n = 3) and reversible hepatic toxicity (n = 1). We conclude that Ketoconazole is an effective inhibitor of cortisol and androgens synthesis. It is well tolerated, rapidly effective and its efficacy persists unchanged for at least one month in all forms of Cushing's syndromes. For these reasons Ketoconazole may be a valuable drug for preoperative treatment of Cushing's syndrome.
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PMID:[Short term effects of ketoconazole in Cushing's syndrome]. 269 87

GAWK (chromogranin-B 420-493) is a 74 amino acid peptide recently isolated from human pituitaries. Using two different antibodies (directed against GAWK [1-17] and [20-38] fragments) GAWK-LI was measured in tumors from 194 patients and in the plasma of 434 patients by RIA. The highest tissue concentrations of GAWK-LI were found in pheochromocytoma (GAWK [1-17]-LI, 18,173 +/- 3,915; GAWK [20-38]-LI, 17,852 +/- 2,763 [mean +/- SEM] pmol/g wet wt tissue; n = 9), which were at least ten times higher than any other tumors producing GAWK-LI. High concentrations of GAWK-LI were also found in other types of endocrine tumors including carcinoid, medullary carcinoma of thyroid, pancreatic, and ACTH-producing lung tumors. On the other hand, low concentrations of GAWK-LI were found in nonendocrine tumors. Plasma concentrations of GAWK-LI were found to be elevated in patients with endocrine tumor, but more so in those with pancreatic tumors than with pheochromocytomas. Plasma concentrations returned to normal after successful tumor removal. Chromatographic profiles of GAWK-LI in extracts of pheochromocytomas and normal adrenals showed high molecular weight peaks that were absent in the extracts of other endocrine tumors and normal pancreas, suggesting differential tissue-specific processing. Thus GAWK-LI is produced by a variety of endocrine tumors and may serve as a plasma tumor marker, especially in patients with pancreatic endocrine tumors.
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PMID:Production of GAWK (chromogranin-B 420-493)-like immunoreactivity by endocrine tumors and its possible diagnostic value. 272 61

Large doses of atrial natriuretic peptide (ANP) inhibit renin and aldosterone secretion in normal man, but the effect of physiological levels is unknown. We, therefore, studied the effect of a low infusion rate of alpha-human ANP (alpha hANP; 0.5 microgram/min for 180 min) on the plasma corticosteroid response to graded physiological doses of angiotensin II (0.5, 1.0, 2.0, and 4.0 ng/kg X min, each for 30 min) and ACTH (6.25, 12.5, 25, and 50 mIU, each for 30 min) in six normal men eating a low salt diet (10 mmol sodium and 100 mmol potassium daily). The angiotensin II and ACTH infusions were given from 0900-1100 h on separate days, during which randomized infusions of placebo or alpha hANP were given from 0800-1100 h according to a single blind protocol. Plasma immunoreactive ANP levels were less than 10 pmol/L on the placebo day compared to 30-50 pmol/L during the alpha hANP infusions, and were not altered by either ACTH or angiotensin II. Compared with the control observations, there was no significant change in arterial pressure or heart rate during either the alpha hANP or angiotensin II infusions. ACTH infusions evoked an incremental response in plasma aldosterone and cortisol, and the dose-response relationship was unaltered by alpha hANP. In contrast, while an incremental and significant increase in plasma aldosterone in response to angiotensin II occurred with the placebo infusion, no significant increase occurred in response to angiotensin during the alpha hANP infusion. The slope of the angiotensin II/aldosterone regression line was significantly less during all alpha hANP infusions compared to that during the placebo infusion (P less than 0.02). In addition, on the ACTH infusion day significant suppression of both PRA (P less than 0.05) and plasma angiotensin II (P less than 0.008) occurred during the alpha hANP infusion compared to that during the placebo infusion, whereas PRA was equally suppressed by angiotensin II in the presence or absence of alpha hANP. alpha hANP also increased urine volume [176 +/- 31 (+/- SEM) vs. 113 +/- 19 mL/mmol creatinine with placebo; P less than 0.03] and sodium excretion (2.14 +/- 0.48 vs. 0.58 +/- 0.22 mmol/mmol creatinine with placebo; P less than 0.004) on the ACTH infusion days. With angiotensin II, urine volume was also significantly increased by alpha hANP (150 +/- 27 vs. 81 +/- 15 mL/mmol creatinine with placebo; P less than 0.03), and urine sodium excretion doubled.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of physiological levels of atrial natriuretic peptide on hormone secretion: inhibition of angiotensin-induced aldosterone secretion and renin release in normal man. 282 Oct 56

An in-vitro perifusion system was used to investigate spontaneous ACTH release from human fetal (21-23 weeks gestation) and adult pituitaries. The pattern of ACTH release from fetal pituitaries (n = 7) exhibited a remarkable pulsatile character with a mean (+/- SEM) pulse interval of 11.3 +/- 0.8 min. The mean pulse amplitude was 49.7 +/- 6.3 pg, with a nadir to peak increment of 90.7 +/- 10.4%. The mean ACTH release rate was 87.2 +/- 13.3 pg/2 min. Addition of the calcium chelator EGTA (4 nM) to the perifusion medium induced a significant (P less than 0.01) decrease in both ACTH release rate (from 102.0 +/- 8.5 to 52.0 +/- 9.9 pg/2 min) and ACTH pulse amplitude (from 57.7 +/- 2.8 to 31.3 +/- 4.6 pg) (n = 3). Administration of either 2 nM corticotrophin releasing factor (CRF) or 56 mM KCl induced 10- and 2-fold increases in ACTH secretion, respectively (n = 2). Quarters of adult human pituitaries (n = 6) also secreted ACTH in a pulsatile fashion, with a pulse interval of 14.8 +/- 1.7 min, pulse amplitude of 86.7 +/- 10.0 pg, nadir to peak increment of 84.5 +/- 9.8%, and overall release rate of 167.2 +/- 8.8 pg/2 min. These studies demonstrate that ACTH release from the isolated human pituitary in vitro is characterized by high frequency/low amplitude pulses, independent of hypothalamic stimulation. Accordingly, this spontaneous calcium-dependent pulsatile ACTH release apparently reflects the activity of an intrinsic intrapituitary pulse-generating mechanism.
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PMID:Intrinsic pulsatility of ACTH release from the human pituitary in vitro. 282 96

Insulin-induced hypoglycemia is a potent stress stimulating ACTH release, but the factors responsible for this ACTH secretion are not known. In this study, several ACTH-stimulating factors, such as CRH, arginine vasopressin (AVP), epinephrine (E), norepinephrine (NE), and dopamine, in addition to ACTH, cortisol, and glucose, were simultaneously measured in plasma before and 15, 30, 60, 90, and 120 min after iv administration of 0.1 U/kg BW regular insulin to seven normal subjects. Insulin administration resulted in significant rises in the mean plasma ACTH level from 4.6 +/- 1.1 (+/- SEM) to 21.6 +/- 4.8 pmol/L at 30 min (P less than 0.01) and in plasma cortisol from 330 +/- 60 to 720 +/- 50 nmol/L at 60 min (P less than 0.01). These increases were preceded by a 41.0 +/- 1.9% (P less than 0.001) fall in blood glucose levels. The mean plasma CRH level rose significantly from 1.0 +/- 0.1 to 1.2 +/- 0.1 pmol/L (P less than 0.01) at 30 min and remained elevated until 120 min. In addition, concomitant and significant rises in plasma AVP levels (basal, 1.5 +/- 0.01; peak, 4.5 +/- 1.1 pmol/L at 30 min; P less than 0.01), E (basal, less than 50; peak, 640 +/- 130 pmol/L at 30 min; P less than 0.01), and NE (basal, 0.07 +/- 0.01; peak, 0.17 +/- 0.03 nmol/L at 60 min; P less than 0.05), but not dopamine, also occurred. These results suggest that multiple ACTH-releasing factors, such as CRH, AVP, E, and NE, are involved in ACTH secretion induced by insulin-induced hypoglycemia in man.
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PMID:Hormonal responses to insulin-induced hypoglycemia in man. 282 51

Gastrin-releasing peptide (GRP; mammalian bombesin) exerts several functions within the hypothalamus and is a putative regulator of pituitary hormone secretion. We investigated the effect of GRP on the secretion of pituitary hormones and cortisol in normal men. GRP was infused iv as primed infusions of 0.12 pmol/kg BW. min for 30 min (GRP I) and 1.50 pmol/kg. min for an additional 30 min (GRP II). GRP dose-dependently stimulated ACTH secretion compared with the effect of saline [net change in ACTH (delta ACTH) before and after treatment: GRP I, 3 +/- 1 (+/- SEM) vs. 0 +/- 1 pmol/L (P less than 0.05); GRP II, 5 +/- 1 vs. -3 +/- 1 pmol/L; P less than 0.01)]. A further increase in plasma ACTH concentration occurred after cessation of GRP infusion (7 +/- 2 vs. 0 +/- 1 pmol/L; P less than 0.025). GRP caused a similar dose-dependent stimulation of cortisol secretion compared with the effect of saline [delta cortisol before and after treatment: GRP I, -19 +/- 21 vs. -68 +/- 14 nmol/L (P less than 0.05); GRP II, 38 +/- 33 vs. -86 +/- 15 nmol/L (P less than 0.005)]. The serum cortisol concentration increased further after cessation of the GRP infusion (72 +/- 31 vs. -124 +/- 33 nmol/L; P less than 0.0025). GRP dose-dependently stimulated beta-endorphin immunoreactivity compared with the effect of saline [delta beta-endorphin immunoreactivity before and after treatment: GRP I, 6 +/- 1 vs. -3 +/- 1 pmol/L (P less than 0.01); GRP II, 11 +/- 4 vs. -6 +/- 2 pg/mL (P less than 0.025)]. GRP had no effect on PRL or GH secretion. We suggest that GRP participates in the neuroendocrine regulation of the secretion of proopiomelanocortin-derived peptides.
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PMID:Corticotropin-releasing activity of gastrin-releasing peptide in normal men. 282 53

The salivary cortisol concentration is an excellent indicator of the plasma free cortisol concentration. To establish its normal and pathological ranges, salivary cortisol concentrations were measured in 101 normal adults, 18 patients with Cushing's syndrome, and 21 patients with adrenal insufficiency. The normal subjects had a mean (+/- SEM) salivary cortisol concentration of 15.5 +/- 0.8 nmol/L (range, 10.2-27.3) at 0800 h and 3.9 +/- 0.2 nmol/L (range, 2.2-4.1) at 2000 h (n = 20). The mean value 60 min after ACTH administration in 58 normal subjects was 52.2 +/- 2.2 nmol/L (range, 23.5-99.4), and it was 1.4 +/- 1.1 nmol/L (range, 1.6-3) at 0800 h in 23 normal subjects given 1 mg dexamethasone 8 h earlier. In patients with primary or secondary adrenal insufficiency (n = 21) the mean salivary cortisol level was 7.5 +/- 0.4 nmol/L (range, 1.9-21.8) 60 min after ACTH. In patients with Cushing's syndrome (n = 7), the mean value after the 1-mg dexamethasone suppression test was 16.1 +/- 7.8 nmol/L (range, 5.8-66.8). No overlap was found between the values in the normal subjects and those in the patients during the dynamic tests. Discrepancies between salivary and total plasma cortisol were found in 8 patients with adrenal insufficiency, which may be explained by the effects of drugs such as thyroid hormones, Op'-dichlorodiphenyldichloroethane, and psychotropic agents. We conclude that salivary cortisol measurements are an excellent index of plasma free cortisol concentrations. They circumvent the physiological, pathological, and pharmacological changes due to corticosteroid-binding globulin alterations and offer a practical approach to assess pituitary-adrenal function.
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PMID:Salivary cortisol measurement: a practical approach to assess pituitary-adrenal function. 282 10

Arginine vasopressin (AVP) regulates ACTH release under certain conditions, and exogenously administered AVP is used clinically to stimulate ACTH secretion. We attempted to determine at what plasma concentration AVP can stimulate ACTH release. Six normal men were given infusions of AVP (Ferring) or vehicle between 1600 and 1700 h on five occasions: 1) saline (30 mL/h); 2) 10 ng AVP/min; 3) 30 ng AVP/min; 4) 100 ng AVP/min; and 5) 300 ng AVP/min. Plasma AVP, ACTH, and cortisol concentrations were measured every 10 min during the infusions. Basal plasma AVP levels were less than 1 ng/L (less than 0.92 pmol/L). The lowest AVP dose raised plasma AVP into the range found in fluid-deprived subjects (7-8 ng/L;6.5-7.3 pmol/L), but had no effect on plasma ACTH concentrations. AVP in a dose of 30 ng/min also had no effect. The 100 ng AVP/min dose raised plasma AVP concentrations to 51.4-65.5 ng/L (46-60 pmol/L). This increase led to a transient insignificant increase in plasma ACTH from 13.9 +/- 1.2 (+/- SEM) ng/L (3.1 +/- 0.3 pmol/L) to 20.0 +/- 1.4 ng/L (4.4 +/- 0.3 pmol/L), while plasma cortisol rose significantly from 146 +/- 10 to 209 +/- 19 nmol/L (P less than 0.01) after 60 min of infusion. The 300 ng AVP/min dose raised plasma AVP levels to about 260 ng/L (239 pmol/L); the maximal plasma ACTH and cortisol levels were 39.5 +/- 5.0 ng/L (8.7 +/- 1.1 pmol/L; P less than 0.01) and 348 nmol/L (P less than 0.01), respectively. Thus, peripheral plasma AVP levels have to be raised high above the physiological range before ACTH release is stimulated. We conclude that any AVP reaching the adenohypophysis through the peripheral circulation is of much less importance for the regulation of ACTH secretion than is AVP derived from the pituitary portal circulation.
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PMID:Effects of incremental infusions of arginine vasopressin on adrenocorticotropin and cortisol secretion in man. 283 Dec 45

The spontaneous glucocorticoid production in control adrenal cells (N = 10) and in the adenoma cells (N = 15) exhibited comparable geometric mean values: 1.896 nmol/ml/4-5 x 10(5) cells per 2 h (confidence limits: 0.428-8.391) and 1.852 nmol/ml (0.326-12.241), respectively. The same results were obtained for the three samples of nodular hyperplasia cells. When cortisol and corticosterone were measured separately, there was no significant difference between the outputs for control cells and those for pathological cells. Baseline aldosterone production in control cells showed a geometric mean of 2.525 pmol/ml (0.236-27.192). In the 15 adenomas, spontaneous production was extremely important: 57.297 pmol/ml (3.357-976.692). The difference was highly significant (P less than 0.0005). Aldosterone levels in the 3 samples of nodular hyperplasia cells were not different from the control values. In 9 out of the 15 adenomas, aldosterone responses to 10(-10) mol/l ACTH, expressed as stimulated/basal production, were above normal: 3.58 +/- 0.86 (SEM) against 1.48 +/- 0.08 (P less than 0.025). In the remaining 6 and in the 3 samples of nodular hyperplasia cells, there was a slight or no response. Angiotensin II (AII) stimulated both adenoma and nodular hyperplasia cells to varying degrees, without any obvious difference between these two categories. A combination of ACTH (10(-12) mol/l) and AII (10(-12) mol/l) had a synergistic action on aldosterone production in cells classed in the adenoma group. These findings demonstrate that despite the abnormal rate of aldosterone formation in adenoma cells, the production rate of corticosterone and cortisol remains normal. They unmask two functional categories with regard to ACTH in the adenoma group. Finally, they underline the relative insensitivity of nodular hyperplasia cells to ACTH.
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PMID:In vitro studies in primary aldosteronism: baseline steroid production and aldosterone responses to ACTH and angiotensin II. 283 82


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