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)

We report on a patient with ACTH and FSH producing invasive pituitary adenoma complaining of cutaneous pigmentation. Elevations in plasma ACTH, beta-endorphin and cortisol levels as well as urinary 17-OHCS and cortisol excretion were found. Serum FSH concentration was just within the upper limit of the normal range, whereas serum LH level was reduced and alpha-subunit level was normal. Roentogenographic examination showed an almost complete loss of sellar floor and destruction of the posterior clinoids and dorsum sella. CT scan and MRI demonstrated an enlarged tumor invasion of the clivus and its extension to the sphenoid sinus. After subtotal removal of the large pituitary tumor, serum cortisol and plasma beta-endorphin levels as well as plasma ACTH concentrations returned to normal and serum FSH levels also remarkably decreased. Histologically, the tumor corresponded to a chromophobe, slightly PAS positive adenoma. These tumor cells exhibited positive immunostaining with antibody to ACTH (1-24), beta-LPH, beta-endorphin and FSH, while immunostaining of the adenoma cells was negative for LH, TSH, GH and prolactin. The immunogold technique also demonstrated ACTH and FSH particles in the secretory granules in the cytoplasm of the adenoma cells. Some of the tumor cells disclosed Crooke's hyalinization and type I microfilament occupied most of the cytoplasm. In the present study, a very rare case of ACTH and FSH producing invasive pituitary adenoma is reported.
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PMID:An ACTH and FSH producing invasive pituitary adenoma with Crooke's hyalinization. 171 63

There is evidence that hypothalamic hormones can regulate hormone secretion by pituitary adenomas. Hormone release by adenomas can be stimulated by hypothalamic releasing peptides; several hypothalamic inhibitory hormones or their analogues are used in the therapy of pituitary tumors to suppress hormone secretion and, in some cases, to reduce tumor size. A role for hypothalamic hormones in the development and growth of pituitary tumors has also been suggested by the association of pituitary adenomas with tumors producing hypothalamic hormones. In particular, tumors producing growth hormone-releasing hormone (GRH) or corticotropin-releasing hormone (CRH) have been associated with hyperplasia of their target adenohypophysial cells; a few have had pituitary neoplasms. Investigations have shown that some adenohypophysial cells respond to sustained stimulation by hypothalamic peptides with cell proliferation, however, it was not proven that the sustained stimulation resulted in the development of tumors. Recently, an animal model of disease was provided by mice transgenic for GRH. At 8 months of age, the mice developed pituitary mammosomatotroph hyperplasia; mice older than 12 months developed pituitary mammosomatotroph adenoma. It is suggested that continued hormonal stimulation plays a role in tumorigenesis, probably by promotion of cell replication.
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PMID:The role of hypothalamic hormones in the pathogenesis of pituitary adenomas. 192 53

Pancreatic tissue from 3 cases of hyperinsulinemic hypoglycemia was examined using histochemical and immunoperoxidase staining techniques. The insular lesions present were adenomatosis and insulin-producing islet-cell adenomata. The great majority of the islet parenchymal cells in these lesions were reactive with antibodies to pro-insulin, C-peptide, and insulin. A variable number of islet cells was found to react with beta-endorphin antiserum in all 3 cases, while the reaction with antiserum against the neural tissue marker antigen, S-100, was restricted to the cases with islet-cell adenoma. Argyrophil parenchymal cells were present in focal adenomatosis but almost absent in insulomata. These results suggest that various lesions of the endocrine pancreas causing hypoglycemia can be distinguished by means of specific histo- and immunocytochemical methods because of differences in the distribution of characteristic cellular antigens.
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PMID:Argyrophil and beta-endorphin immunoreactive cells in focal islet-cell adenomatosis and insulin-producing islet-cell adenomata. 196 54

Among 436 patients with hypertension unrelated to any renal lesion, renovascular damage, pheochromocytoma, Cushing's syndrome or hyperthyroidism, 15 patients had low plasma renin activity (PRA) and elevated plasma aldosterone concentrations in the upright position and resultant high aldosterone/PRA ratios: 8 with aldosterone-producing adenoma (APA; group 1) and 7 with idiopathic hyperaldosteronism (IHA; group 2). Thirty-nine patients had suppressed PRA in the presence of normal plasma aldosterone levels and moderately elevated aldosterone/PRA ratios (group 3). Thirty of them had elevated plasma 11-deoxycorticosterone (DOC) and 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) concentrations (group 3a) and 9 of them had normal levels of those mineralocorticoids (group 3b). The rest of them (382 patients) had low aldosterone/PRA ratios (group 4). Adrenal scintigraphy with dexamethasone pretreatment revealed [13I]-cholesterol accumulation not only in patients with APA (unilateral) or IHA (bilateral), but also in patients of group 3a (bilateral). In patients in groups 3a and 3b adrenal size (especially thickness), as measured by computed tomography (CT scan), was enlarged, as in patients with IHA (group 2), and was significantly greater than in patients of group 4 (p less than 0.001). Spironolactone reduced blood pressure in all tested patients of group 3a, and the removal of adrenal tumor or hyperplastic tissue normalized blood pressure in patients of groups 1, 2 and 3a. Excised adrenal glands exhibited cortical hyperplasia with or without nodular hyperplasia in patients of group 3a. Good agreement was found between the actual size of the excised tissue and the measurement obtained by CT scan. Since beta-endorphin and beta-lipotropin were depressed in patients of group 3a, it is suggested that an unknown pituitary substance stimulates the adrenal cortex to release too large amounts of DOC and 18-OH-DOC and inappropriate secretion of aldosterone.
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PMID:Inappropriate elevation of the aldosterone/plasma renin activity ratio in hypertensive patients with increases of 11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone: a subtype of essential hypertension? 207 Mar 75

The silent corticotroph-cell adenoma (SCCA) is characterized by the presence of immunoreactive adrenocorticotropic hormone (ACTH) in the tumor tissue in patients without symptoms of Cushing's disease. To elucidate the pathophysiology of SCCA, the expression of pro-opiomelanocortin (a ACTH precursor) genes was studied in a patient with SCCA and in three patients with Cushing's disease. Pro-opiomelanocortin messenger ribonucleic acid (mRNA) was found in the SCCA tissue to a greater degree than in the adenomas of the patients with Cushing's disease. Northern blot analysis revealed that the size of pro-opiomelanocortin mRNA present in the SCCA tissue was indistinguishable from that in the adenomas associated with Cushing's disease. A ribonuclease mapping study indicated that there were no point mutations in the coding sequence of pro-opiomelanocortin mRNA present in the SCCA tissue. Because of the presence of pro-opiomelanocortin mRNA and immunoreactive ACTH in the adenoma tissue, it is proposed that translation of the mRNA and subsequent accumulation of ACTH precursor occurred in the SCCA. Thus, the absence of Cushing's disease symptoms in this SCCA could not be caused by abnormality in the coding sequence of the pro-opiomelanocortin gene or in ribonucleic acid processing. The occurrence of abnormality at or after the translational steps was strongly suggested.
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PMID:Pro-opiomelanocortin gene expression in silent corticotroph-cell adenoma and Cushing's disease. 215 97

We examined the direct effects of corticotropin-releasing hormone (CRH) and cortisol on the morphology of cells from 6 functioning human pituitary corticotroph adenomas in culture using both light and electron microscopic morphometry and correlated the structural changes with alterations in adrenocorticotropin (ACTH) release in each case. During incubations lasting 2 or 24 h, ACTH release was increased by CRH and reduced by cortisol. After incubations lasting from 2 to 72 h, light microscopic morphometric analysis showed no significant differences in cell size, nuclear area, cytoplasmic area or nuclear/cytoplasmic ratio between treated and control adenoma cells. Ultrastructural morphometry documented increased cytoplasmic volume density (CVD) of rough endoplasmic reticulum and/or Golgi apparatus and reduced CVD of secretory granules in cells incubated with CRH. There was no consistent change in CVD of endoplasmic reticulum, Golgi apparatus or secretory granules in adenoma cells incubated with cortisol, but in all tumors there were marked filament accumulations indicating a direct effect of cortisol on adenomatous corticotrophs. The changes were similar after 2- and 72-hour exposures. These results indicate that (1) some adenomatous corticotrophs can respond to CRH and cortisol; (2) the morphologic changes observed in cells treated with CRH correlate with increased ACTH release, and (3) accumulation of filaments is the direct effect of cortisol and is associated with reduced ACTH release.
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PMID:Human pituitary corticotroph adenomas in vitro: morphologic and functional responses to corticotropin-releasing hormone and cortisol. 215 92

Petrosal sinus sampling was performed 171 times in 157 patients with known or suspected Cushing disease. In all cases, samples for measuring adrenocorticotropic hormone (ACTH) levels were obtained from both inferior petrosal sinuses and a peripheral vein, both before and after intravenous corticotropin-releasing hormone (CRH) administration. In seven examinations in seven patients, a ratio, or gradient, between the ACTH levels in the inferior petrosal sinuses existed in the samples obtained prior to CRH stimulation; however, poststimulation samples demonstrated reversal of the gradient, suggesting lateralization to the contralateral side of the pituitary gland. Data from surgical exploration of the pituitary gland were available for six of these patients, all of whom had adenomas. Prestimulation samples provided correct lateralization in three patients, and in two patients the poststimulation samples provided correct lateralization. One patient had a midline adenoma. When the results of pre- and poststimulation petrosal sinus sampling conflict, neither can be relied on uniformly to provide correct lateralization of ACTH-secreting pituitary adenomas.
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PMID:Petrosal sinus sampling: discordant lateralization of ACTH-secreting pituitary microadenomas before and after stimulation with corticotropin-releasing hormone. 216 35

The purpose of this study was to ascertain whether the pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in "non-functioning" adrenocortical adenoma would uncover a functional activity in these adrenal nodules. Eleven patients with incidentally discovered "silent" adrenocortical adenoma and eleven controls were studied. The initial clinical and laboratory examination, including an overnight 1 mg dexamethasone suppression test, revealed no abnormalities in any of the subjects. IR-ACTH and serum steroids (F, S, P, 17OHP, 18OHB, and aldosterone) were normal in both controls and patients. After pulse IV injection of 100 micrograms hCRH, the cortisol response was significantly exaggerated (P = 0.01). Stimulated plasma ACTH levels were, however, significantly lower in patients than in controls (P = 0.01), indicating counter-feedback regulation of cortisol. The peak cortisol/peak ACTH ratio (Fmax/ACTHmax) in the patients was significantly elevated (26.8 +/- 4.37 nmol/ng vs. 14.6 +/- 2.16 nmol/ng, P = 0.02). Two further patients with incidentally discovered "pre-Cushing's" adrenocortical adenoma displayed an even higher ratio (43.5 and 45.5 nmol/ng). In established Cushing's syndrome due to an autonomous adrenocortical adenoma, suppression of ACTH and of the ACTH response to hCRH occurs with a very high basal cortisol/basal ACTH ratio. Our findings suggest some functional activity even in clinically "silent" adrenocortical adenoma. Response to hCRH uncovers a continuous spectrum between adrenocortical adenoma, "pre-Cushing's", and Cushing's syndrome.
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PMID:Endocrine activity of the "silent" adrenocortical adenoma is uncovered by response to corticotropin-releasing hormone. 216 44

The distribution of pro-opiomelanocortin (POMC) messenger RNA (mRNA) in 7 functional and 17 clinically silent corticotropic adenomas was analyzed by in situ hybridization (ISH) with 35S-labeled oligonucleotide probes using formalin-fixed paraffin-embedded tissue sections cut from blocks that were in storage between 1 to 14 years. All 7 functional adenomas and 4 subtype 1 tumors had detectable POMC mRNA, while 3 of 6 subtype 2 and 1 of 7 subtype 3 silent adenomas contained detectable POMC mRNA. In situ hybridization analysis with an 35S-labeled beta-actin probe showed a positive hybridization signal in 22 of 22 cases, indicating that the absence of detectable POMC mRNA in some adenomas was not due to loss of the mRNAs during processing of the tissues or because of the age of the embedded tissue blocks. Northern hybridization analysis with the oligonucleotide probes in 2 normal pituitaries and an adenoma causing Cushing's disease detected a 1.2-Kb mRNA in all three tissues, indicating that the oligonucleotide probes were very specific. These results indicate that subtype 1 silent adenomas and clinically active adenomas associated with Cushing's disease contain POMC mRNA that is readily detectable by ISH in routinely processed tissue specimens, while only a few of the subtypes 2 and 3 adenomas have POMC mRNA that can be detected in paraffin blocks with the oligonucleotide probes used in this study.
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PMID:Analysis of endocrine active and clinically silent corticotropic adenomas by in situ hybridization. 216 13

This study explores the possibility of improving endocrinologic testing during petrosal sinus catheterization by determining both beta-endorphin and corticotropin (ACTH). We studied 14 patients with Cushing's disease, two with adrenal tumor, and three with ectopic tumors secreting ACTH. In patients with Cushing's disease, beta-endorphin concentrations paralleled those of ACTH in all basal plasma samples collected either from petrosal sinuses or peripheral veins. Individual responses of beta-endorphin and ACTH to corticotropin releasing hormone (CRH) were closely related to the presence of a corticotroph adenoma. In such patients, a consistently higher concentration of beta-endorphin over ACTH was observed in all samples collected either from petrosal sinuses or peripheral veins; the ratios were unchanged after the administration of CRH. In patients with ectopic ACTH secretion, the mean ratio of beta-endorphin over ACTH (with both values expressed in pmol/L) was significantly higher (3.5) than that of patients with Cushing's disease (2.9) or Cushing's syndrome due to adrenal tumor (2.7).
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PMID:Parallel assays of beta-endorphin and ACTH in Cushing's patients undergoing petrosal sinus sampling. 217 14


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