Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bilateral and simultaneous sampling of the inferior petrosal sinuses in patients with Cushing's disease has been used to establish the presence and laterality of adrenocorticotropic hormone (ACTH)-producing microadenomas prior to transsphenoidal surgery. Successful preoperative lateralization depends upon equivalent dilution of pituitary venous blood on the two sides since samples which are diluted by unequal amounts of non-pituitary blood may lead to erroneous results. To assure valid sampling results, the use of other pituitary hormones, measured simultaneously, has been proposed to correct the ACTH concentrations from the inferior petrosal sinuses against unequal dilution by non-pituitary venous blood. This proposal presumes that ACTH-secreting microadenomas will not cause unequal delivery of the other pituitary hormones into the two inferior petrosal sinuses. The inferior petrosal sinus concentrations of prolactin (PRL), thyrotropin (TSH), and the alpha subunit of human chorionic gonadotropin (alpha-HCG) were evaluated as indicators of pituitary venous blood dilution in 11 patients with Cushing's disease. Four patients with ectopic ACTH syndrome served as controls. Blood was withdrawn simultaneously from catheters in both inferior petrosal sinuses and from a peripheral vein for measurement of ACTH, PRL, TSH, and alpha-HCG. The ACTH concentrations were then corrected for dilution by non-pituitary blood by dividing the ACTH concentration from each side by the ratio of the inferior petrosal sinus to peripheral blood concentrations of PRL, TSH, and alpha-HCG for that side. At surgery, all 11 patients had ACTH-secreting microadenomas on the side predicted by the uncorrected ACTH concentrations. However, in three patients the corrected ACTH values would have led to erroneous results. Among the 18 sets of corrected inferior petrosal sinus measurements in these three patients, the corrected ACTH values failed to show an inferior petrosal sinus gradient in six and localized the tumor to the side opposite the adenoma in four. Incorrect lateralization was obtained with each of the hormones (PRL, TSH, and alpha-HCG) used for correction. Furthermore, the ipsilateral (side of tumor)-to-contralateral inferior petrosal sinus gradient of ACTH in patients with Cushing's disease was generally paralleled by a significant inferior petrosal sinus gradient of PRL, TSH, and alpha-HCG to the side of the tumor, whereas patients with the ectopic ACTH syndrome tended not to exhibit lateralizing (side-to-side) gradients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Usefulness of inferior petrosal sinus venous endocrine markers in Cushing's disease. 282 70

The effects of ovine corticotropin releasing factor (o-CRF) on plasma aldosterone, 18-OH-corticosterone (18-OHB), plasma adrenocorticotropin (ACTH) and cortisol were determined in eight patients with primary aldosteronism, six with aldosterone-producing adenoma (APA) and two with idiopathic hyperaldosteronism (IHA). The results were compared with those in six normal subjects and eleven patients with essential hypertension (EHT, 5 with low renin and 6 with normal renin). In patients with APA, the peak plasma aldosterone and 18-OHB responses to 100 micrograms iv of o-CRF (226% and 113% increase from baseline, respectively) were greater than those in EHT and normal subjects. The net integrated aldosterone and 18-OHB responses (840 +/- 156, and 419 +/- 121 ng/dl.hr, respectively) were also significantly greater (p less than 0.01) in APA than those in normals and EHT. In two patients with IHA, both the peak and net integrated aldosterone response were smaller than those in APA, in spite of nearly identical plasma ACTH and cortisol responses. These results suggest that augmented responses of mineralocorticoids to o-CRF may be characteristic of aldosteronism due to APA, mediated by CRF-induced ACTH, and possibly other proopiomelanocortin (POMC)-derived peptides.
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PMID:Effects of corticotropin-releasing factor (CRF) on aldosterone and 18-hydroxycorticosterone in essential hypertension and primary aldosteronism. 283 82

The effects of corticotropin-releasing hormone (CRH) and dexamethasone on proopiomelanocortin (POMC) mRNA levels in cultured pituitary adenoma cells were studied in 10 patients with Cushing's disease. As a control, POMC mRNA levels in cells from nonadenomatous tissues were examined in four patients. Human POMC mRNA in the cells was analyzed by Northern blot hybridization. Human POMC DNA probe hybridized with only a single size class of RNA (approximately 1,200 nucleotides) from the adenoma and nonadenoma cells of each patient. The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone. CRH increased POMC mRNA levels in these cells in a dose- and time-dependent manner. The minimum concentration of CRH required to elevate POMC mRNA levels in these cells exposed for 15 h was 0.1 nM. The minimum duration of 1 nM CRH treatment required to increase these levels was 3 h under our conditions. Inhibitory effects of 1 and 10 micrograms/dl dexamethasone on ACTH release and POMC mRNA levels in nonadenoma cells were greater than those in adenoma cells. These results suggest the following: (a) that the mRNA in cultured pituitary adenoma cells is qualitatively the same as that in vivo; (b) that responses of mRNA levels to CRH are time- and dose-dependent; and (c) that adenoma cells resist the inhibitory effect of dexamethasone on POMC mRNA levels and ACTH release.
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PMID:Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro. 283 42

An immunocytochemical study was performed by the indirect peroxidase method on the pituitary tumour of 37 patients with clinical and biological signs of silent adenoma. Antisera were used against human PRL, human GH, ACTH1-24, human ACTH17-39, alpha-melanocyte stimulating hormone (alpha-MSH), human beta-endorphin, alpha-subunit of hCG (hCG-alpha), and beta-subunits of human LH (LH-beta), human FSH (FSH-beta) and human TSH (TSH-beta). Immunostaining in at least 5% of the tumour cell population, with one or more antisera, was present in 13 cases; hCG-alpha immunostaining was the one most frequently observed. Combined immunostaining was found in 7 cases. Exclusive immunostaining was present in 6 cases: 4 with hCG-alpha, 1 with ACTH1-24 and 1 with TSH-beta. It is concluded that a significant number of silent pituitary adenomas show a certain secretory pattern of pituitary hormones or subunits of glycoprotein hormones as revealed by the immunocytochemistry.
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PMID:The immunocytochemical heterogeneity of silent pituitary adenomas. 284 Jul 93

Clinical and in-vitro investigations have been performed on a corticotroph adenoma removed from a patient suffering from Cushing's disease. Prior to surgery, the patient's Cushing's disease had been successfully controlled, clinically and biochemically, by long term administration of bromocriptine. After selective adenomectomy, tumour tissue was investigated by a perfused isolated cell column technique. It was shown that the tumour cells secreted immunoreactive- (IR)- ACTH and IR-alpha-MSH and that the release of both peptides was promptly suppressed by dopamine. Chromatographic analysis of the secreted IR-alpha-MSH revealed a high proportion of acetylated alpha-MSH; smaller amounts of desacetyl alpha-MSH and diacetyl alpha-MSH were present. The relevance of these findings to the proposal that certain corticotroph adenomas are derived from the intermediate lobe of the pituitary is discussed. It is concluded that there is little direct evidence for involvement of the residual zona intermedia of the adult human pituitary in the development of Cushing's disease.
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PMID:A bromocriptine-responsive corticotroph adenoma secreting alpha-MSH in a patient with Cushing's disease. 284 47

Arginine vasopressin (AVP) is a potent secretagogue for adrenocorticotropin (ACTH) release from normal corticotropes and from ACTH-secreting pituitary adenoma cells. To explore the mechanism underlying this action, we investigated the effects of AVP on Ca2+-dependent action potentials and Ca2+ currents in cultured human ACTH-containing pituitary tumor cells (hACTH adenoma cells). Pituitary adenoma fragments removed at surgery from two patients with Cushing's disease were dispersed, and the isolated cells were grown in monolayer culture. Most of the cells showed ACTH immunoreactivity that persisted even after as much as 2 months in culture. Current clamp and voltage clamp recordings were carried out using the patch-clamp technique in the whole cell configuration. AVP produced an increase in the amplitude and duration of action potentials in these cells, and substantially enhanced the transient after-hyperpolarization after each spike. Under voltage the transient after-hyperpolarization after each spike. Under voltage clamp, hACTH adenoma cells showed two Ca2+ current components: a low-threshold, rapidly inactivating (T-type) current; and a higher threshold, slowly inactivating (L-type) current. AVP markedly increased the amplitude of the L-type current without affecting the T-type current. These data suggest that AVP may enhance Ca2+ entry associated with action potentials by potentiating the activity of L-type Ca2+ channels. The resulting rise in cytosolic free Ca2+ may be a key link in the process by which AVP stimulates ACTH release in the pituitary.
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PMID:Vasopressin enhances a calcium current in human ACTH-secreting pituitary adenoma cells. 284 18

Lectin binding sites of adrenocorticotropic hormone (ACTH) secretory granules of human pituitary adenomas and of nonadenomatous pituitary tissue adjacent to adenomas were studied by postembedding immunocytochemical doublestaining on ultrathin sections followed by electron microscopy. The specific hormones produced by the secretory granules were identified by labeling one side of the section with anti-human pituitary hormone antibodies conjugated to gold particles. Simultaneously, the other side was labeled with horseradish peroxidase-lectin to reveal lectin binding sites. Specimens were obtained from four human ACTH-producing pituitary adenomas and from nonadenomatous pituitary tissue surrounding three other adenomas. The four ACTH-producing adenomas showed either weak or negative reactions with concanavalin A, whereas the nonadenomatous ACTH-producing pituitary cells reacted strongly with concanavalin A. Moreover, ACTH secretory granules were significantly larger in the nonadenomatous cells than in adenoma cells. Differences in biochemical structure and ultrastructure between nonadenomatous (normal) pituitary cells and adenoma cells secreting the same specific hormones were demonstrated, and the clinical implications of the results were discussed.
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PMID:Differences in glycoconjugates of adrenocorticotropic hormone-secretory granules between nonadenomatous pituitary cells and adenoma cells as detected by double labeling. 284 95

The response of the sympathoadrenal system to hypoglycaemia of different etiology was studied in seven infants, aged 10-189 days. Five infants had hyperinsulinism secondary to nesidioblastosis or to a beta-cell adenoma of the pancreas, one infant had neonatal sepsis due to staphylococcal infection and one infant congenital growth hormone (HGH) and adrenocorticotropic hormone (ACTH) deficiency. In babies with hyperinsulinism, plasma noradrenaline increased from 0.29 +/- 0.03 to 0.61 +/- 0.09 ng/ml (P less than 0.01), whereas adrenaline increased only in three, but did not change in two babies. Increases in heart rate and blood pressure paralleled these changes. In hypoglycaemia due to congenital sepsis, noradrenaline increased from 0.39 to 1.64 ng/ml and adrenaline from 0.05 to 0.86 ng/ml. This was associated with marked haemodynamic changes. In congenital HGH and ACTH deficiency, the low basal plasma levels of noradrenaline (0.12 ng/ml) and adrenaline (0.01 ng/ml) remained unchanged in response to hypoglycaemia. Heart rate and blood pressure were unaffected. The sympathoadrenal system was activated by hypoglycaemia in all infants except in congenital HGH and ACTH deficiency. In contrast to adults, noradrenaline was the preferentially released catecholamine, suggesting an involvement of noradrenaline in glucose counter regulation in infancy.
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PMID:Sympatho-adrenal response to hypoglycaemia in infants. 285 Sep 15

In an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.
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PMID:Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. 285 94

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81


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