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)

Cells isolated from five aldosterone-producing adenomas were used to study glucocorticoid and aldosterone production in response to ACTH, angiotensin II (A II), and peptides derived from proopiomelanocortin (POMC), viz. the 16K N-terminal fragment (16K) and its derivative, gamma 3MSH and the C-terminal fragment beta-lipotropin (beta LPH) and its derivative beta-endorphin. At concentrations similar to those of ACTH and A II (10(-12)-10(-10) M), 16K, gamma 3MSH, and beta LPH selectively stimulated aldosterone production, which reached levels close to those obtained with A II. ACTH, however, was the most effective stimulant of steroidogenesis. The 16K, gamma 3MSH, and beta LPH peptides potentiated the action of ACTH, particularly in the case of aldosterone production. beta-Endorphin, whether used alone or in association with ACTH, had no effect on steroidogenesis at the dose used (10(-10) M). The principal glucocorticoid products of the adenoma cells were cortisol and corticosterone. The ratios of corticosterone to cortisol (B/F) and aldosterone to corticosterone (A/B) varied considerably from one adenoma to another, both basally and in response to ACTH. Nevertheless, within individual adenomas, the mean B/F ratio induced by ACTH [0.280 +/- 0.013 (+/- SEM)] was significantly larger than that induced by A II (0.127 +/- 0.007; P less than 0.001). By contrast, the A/B ratio in response to ACTH (0.061 +/- 0.003) was significantly smaller than that in response to A II (0.159 +/- 0.010; P less than 0.001). The values obtained with 16K (B/F, 0.106 +/- 0.010; A/B, 0.192 +/- 0.028) and gamma 3MSH (B/F, 0.122 +/- 0.012; A/B, 0.178 +/- 0.020) were close to those obtained with A II. 16K and gamma 3MSH potentiated ACTH's effect on steroidogenesis mainly by increasing the A/B ratio from 0.061 +/- 0.003 for ACTH alone to 0.100 +/- 0.008 for 16K plus ACTH (P less than 0.005) and to 0.092 +/- 0.005 for gamma 3MSH plus ACTH (P less than 0.001). The findings suggest that the stimulation of aldosterone production by 16K and gamma 3MSH in aldosteronoma cells is of the A II type and that these peptides may play a role in the genesis of primary aldosteronism.
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PMID:Effects of proopiomelanocortin peptides and angiotensin II on steroidogenesis in isolated aldosteronoma cells. 299 20

The cytoplasmic secretory granules of corticotrophs in the anterior pituitary are basophil in trichrome stains and periodic acid-Schiff positive in the histochemical stain for glycoprotein due to their content of the glycosylated 16 000 N-terminal fragment of the precursor protein proopiomelanocorticotrophin (POC). The granules show a positive immunocytochemical reaction to antibodies raised against ACTH, beta-endorphin and N-terminal fragments of POC. A small subset of corticotrophs contains immunoreactive alpha MSH in addition. Immunocytochemistry shows the corticotrophs to constitute about 15-20% of the anterior pituitary cells arranged both singly and in clumps. They are distributed in the median wedge and anteriorly, laterally and posteriorly adjacent to the pars nervosa which is often 'invaded' by corticotroph basophils. The alpha MSH subset is prominent in the rudimentary intermediate lobe and is scattered anteriorly in the pituitary of the human fetus. Crooke cell hyalinization is associated with pathologically maintained hypercortisolaemia and with glucosteroid therapy. The hyalinization is demonstrated in ultrastructure to be due to massive accumulation of intermediate cytoplasmic filaments 7-8 nm in diameter that are normally present in only small number. The change is associated with a varying degree of loss of secretory granules. In untreated Addison's disease there is a marked increase in the number of corticotrophs, many of which are arranged in distended alveoli to form micronodules. The vast majority of cases of pituitary-dependent Cushing's disease and all cases of Nelson's syndrome are associated with a basophil or chromophobe adenoma. These give a positive immunocytochemical reaction with anti-ACTH, beta-endorphin and N-terminal POC. In ultrastructure the cells of the chromophobe adenomas are seen to contain sparse secretory granules that are usually smaller than those in the chromophil adenomas. There are only very few reports of pituitary-dependent Cushing's disease found to be due to immunocytochemically confirmed corticotroph hyperplasia with or without a corticotroph adenoma. A few cases have been described in which the adenoma cells show Crooke's hyalinization, associated in one example with secretion of a big ACTH found more typically in ectopic ACTH-secreting tumours. A group of cases due to corticotroph adenoma has been reported whose excessive ACTH secretion is reduced by treatment with the dopamine agonist bromocriptine, in which it is suggested that the tumour cells arise from a subset of corticotrophs of pars intermedia origin.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Histopathology of the pituitary. 300 76

In order to elucidate the mechanism responsible for ectopic hormone production in tumors, biosynthesis of ACHT and related peptides was studied in the pituitary and tumors at levels. In vitro biosynthesis of the ACTH/beta-LPH precursor directed by mRNA extracted from the pituitary and tumors showed no difference in translation products. It is highly likely, therefore, that different final products produced in the pituitary and tumors are caused by different posttranslational processing, such as proteolysis and glycosylation of translation products. The RNA blot analysis of tumors revealed mRNA identical to that of the pituitary. In certain tumors, however, there were larger or smaller mRNA hybridized with an ACTH/beta-LPH precursor probe, in addition to mRNA of normal size. Further studies with endonuclease S1 mapping have provided evidence suggesting that the larger one was probably produced by abnormal splicing of RNA precursor and that the smaller one was resulted possibly from aberrant transcription of the gene. The Southern blot analysis revealed no difference in restriction DNA fragments between the pituitary and tumors, indicating no evidence of gene rearrangement. From these studies, it is conceivable that ectopic ACTH production is resulted from abnormalities in the regulatory mechanism of gene expression. To further study the mechanism regulating the expression of the ACTH/beta-LPH precursor gene, human gene was transfected to mouse pituitary ACTH-producing adenoma cells (AtT-20) and fibroblasts (L-cell). The introduced human ACTH/beta-LPH precursor gene was expressed in AtT-20 cells and suppressed by glucocorticoids to an extent similar to the suppression of mouse gene. On the other hand, possible aberrant transcripts were observed in mouse L cells. It is likely, therefore, that there is a regulatory mechanism, probably "trans" acting, in the pituitary ACTH-producing producing cells and similar mechanism, though not identical, could be exerted in ectopic ACTH-producing tumors.
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PMID:[Hormone production and abnormalities in gene expression in tumors]. 300 63

The effect of LH-RH (25 micrograms as a single i.v. bolus) on plasma corticotropin (ACTH) levels and beta-endorphin-like immunoreactivity was studied at 30 and 60 min in eight women with Nelson's syndrome. Plasma ACTH concentrations increased in three of them, while beta-endorphin-like immunoreactivity, measured in six cases, rose significantly at 30 min in all the patients under investigation. In the control group containing seven women with Nelson's syndrome, placebo (0.9% sodium chloride) administration did not induce any significant changes in ACTH concentrations or in beta-endorphin-like immunoreactivity. Our results suggest that a paradoxical stimulatory influence of LH-RH on pituitary Nelson's adenomas may play an important role in the adenoma hormonal activity and, perhaps, growth. Such an effect could be responsible for a rapid development of some pituitary neoplasms during pregnancy.
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PMID:Plasma ACTH levels and beta-endorphin-like immunoreactivity following administration of luteinizing hormone-releasing hormone in Nelson's syndrome. 301 30

Two patients with ectopic pituitary adenomas and biopsy-proven normal anterior pituitaries are described. Both tumors were located in the sphenoid sinus. One tumor produced prolactin, and the other one was a plurihormonal adenoma that produced predominantly adrenocorticotropin and to a lesser extent thyroid stimulating hormone and alpha subunit. The patient with the plurihormonal tumor, who had Cushing's disease, was cured by surgery while the patient with the prolactinoma was treated by surgery and medical therapy. A review of these two cases and an additional nine cases from the literature of ectopic pituitary adenomas in patients with normal intrasellar anterior pituitaries indicate that these uncommon tumors are capable of secretory function and may be the only cause of excessive pituitary hormone production.
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PMID:Ectopic pituitary adenomas with normal anterior pituitary glands. 301 37

Tissues from 12 human corticotropin-secreting adenomas, obtained during surgery for Cushing's disease (CD, ten cases) or Nelson's Syndrome (NS, two cases), were exclusively mechanically dispersed. Single cells and cell aggregates were plated on extracellular matrix derived from bovine corneal endothelia. Functional responses to physiological stimuli were analyzed by measuring human beta-endorphin (beta h-EP) immunoreactivity (IR) by radioimmunoassay in the culture medium. All adenomas responded with stimulated secretory activity to arginine vasopressin (AVP), corticotropin-releasing factor (CRF), or both. Cortisol higher than 10(-8) M suppressed basal secretion and CRF- or AVP-stimulated beta h-EP-IR secretion. There was no consistent difference in response of the cells when cultured in medium containing 10% fetal calf serum (FCS) or in serum-free conditions. A change of cells from serum to serum-free conditions usually resulted in 10%-50% reduction in the basal secretion level that remained stable for at least 2 weeks and, in one case (NS), 10 weeks. In cells maintained in medium supplemented with 5% serum obtained from the respective patients 40 min after adenoma removal, basal secretion was suppressed to 60% of the baseline level in a 10% FCS control. Long-term incubation with CRF (10(-9) M) showed sustained stimulation of hormone secretion. No remarkable cell proliferation was observed under basal conditions or during long-term, low-dose incubation with cholera toxin (10(-12) M) in two cases (CD), or CRF (10(-9) M) in two cases (NS, CD). Parallel beta-EP-IR and adrenocorticotropin secretion was verified in selected cases.
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PMID:Long-term culture of human corticotropin-secreting adenomas on extracellular matrix and evaluation of serum-free conditions. Secretory aspects. 302 31

It has been suggested that a proportion of the adenomas and the nodular hyperplasia of cells in the pituitary gland in cases of Cushing's disease are derived from cells of the pars intermedia rather than the pars anterior. The evidence can be summarized as follows: the posterior site of adenoma or nodular hyperplasia in the pituitary, the innervation of cells and the suppressive response to the dopamine agonist bromocriptine in vivo or to dopamine in vitro. All these observations infer analogy with cells of the pars intermedia of other species, which are controlled by direct neural tonic dopaminergic inhibition. The adult human pituitary gland, however, does not possess a morphologically distinct pars intermedia, due to regression of the rudimentary fetal pars intermedia after birth, with mixing of cells into the pars anterior and pars nervosa. Since cells of the pars intermedia characteristically synthesize alpha-MSH, we have studied this peptide in order to assess the occurrence and distribution of intermedia-derived cells in the adult human pituitary. Sections from 100 pituitaries, removed at autopsy, were stained by an indirect immunoperoxidase technique using non-cross-reacting antisera specific for alpha-MSH and ACTH. Immunoreactive alpha-MSH (IR-alpha-MSH) cells were found in a total of 97 specimens. Of these, only ten cases showed a marked concentration of IR-alpha-MSH cells in the zona intermedia. In the majority of pituitaries, IR-alpha-MSH cells were more commonly seen in the pars anterior than in the zona intermedia; in 41 cases, IR-alpha-MSH cells were completely absent from the zona intermedia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The distribution of immunoreactive alpha-melanocyte-stimulating hormone cells in the adult human pituitary gland. 302 27

Pituitary adenomas containing adrenocorticotropic hormone (ACTH) in one case, and ACTH, beta-lipotropin, and beta-endorphin in the other, were demonstrated in two patients who had amenorrhea-galactorrhea and hyperprolactinemia with no manifestation of Cushing's disease. Neither adenoma contained prolactin (PRL). Initial bromocriptine therapy resulted in cessation of amenorrhea-galactorrhea and normalization of PRL levels. However, there was radiologic evidence of tumor enlargement in both patients. After pituitary adenomectomy, the two patients resumed regular menses and normal PRL dynamics. These patients illustrate the need for bromocriptine therapy for possible enlargement of their pituitary adenomas. The diagnosis of silent corticotroph adenoma should be kept in mind.
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PMID:Hyperprolactinemia associated with clinically silent adenomas: endocrinologic and pathologic studies; a report of two cases. 303 94

Sixty-one pituitary corticotroph adenomas from 47 patients with Cushing's disease, 10 with Nelson's syndrome, and four eucorticoid patients were studied by light microscopy, immunoperoxidase, and electron microscopy. Seventy nine percent of all tumors and 70% of Nelson's cases were microadenomas, sometimes minute. A contiguity between the posterior lobe and the adenoma was seen in ten cases. Spontaneous infarction of the tumor with remission of Cushing's syndrome occurred in one case. Light microscopy revealed that the adenoma cells were basophilic and contained PAS-positive granules also staining with Herlant tetrachrome and lead-hematoxylin. The granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH), beta-lipotropic hormones (beta-LPH) and beta-endorphin. The most characteristic ultrastructural finding was the presence of perinuclear bundles of microfilaments found in all our cases. Oncocytic changes were seen in three tumors. Four silent corticotroph adenomas, two of them originally microadenomas that had enlarged to enclosed adenomas while being treated with bromocriptine for hyperprolactinemia and one a large diffuse invasive tumor, did not differ in their microscopic, immunocytological, or ultrastructural features.
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PMID:Human corticotroph cell adenomas. 303 31

Pituitary adenomas are usually classified according to the nature of their proper hormonal production. Silent adenomas of the pituitary are tumors without clinical and biochemical evidence of overproduction of any known adenohypophyseal hormones. The proportion of such seemingly nonfunctioning tumors is 20 to 30%. Silent corticotropic adenomas are able to synthesize some normal or abnormal sequences of proopiomelanocortin precursor without any signs of hypercorticism. These tumors were divided into basophilic adenomas with strong periodic acid-Schiff (PAS) positivity and chromophobic adenomas with moderate or no PAS positivity. All of our cases were chromophobic adenomas. Two of the cases were positive for beta-endorphin by immunofluorescence. ACTH immunoreactivity was not present in the cells. Electron microscopic study of the adenoma cells showed small secretory granules with a halo. The diameter of these granules varied from 50 to 250 nm. Automated morphometric and densitometric investigations of silent corticotropic adenomas and adenomas from patients with Cushing's disease gave different karyometric results. The most important practical problem arising from the present investigation was the high frequency of recurrence of silent corticotropic tumors.
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PMID:[Immunohistological determination of beta-endorphin in chromophobe, clinically hormone-nonproducing hypophyseal adenomas]. 316 Dec 55


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