ISSN:1663-2818    

DOI:10.1159/000179288

出版商:S. Karger AG    

年代:1980

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000179289

出版商:S. Karger AG    

年代:1980

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000179290

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

As early as 1932, basophil cells have been considered to be involved in the corticotropic and melanotropic functions due to their proliferation during Cushing’s disease. Later on, opposite opinions were held and other cells suggested to be implied in the tumor process: chromophobe, acidophil or even follicular cells. Moreover, new categories of basophil cells have been evidenced through sophisticated staining methods, in animal and human pituitaries. At the same time, the prevalent dogma ‘one hormone-one cell’ raised the problem of the search for both a corticotroph and a melanotroph in the human pituitary, which is devoid of an intermediate lobe. Since 1960, immunocytochemistry became a reliable method and simultaneously new peptides have been found. However, these peptides share common sequences of amino acids, thus raising questions as to the specificity of the antisera. Most authors mention the reaction to the basophil cells previously considered as melanotrophs and called β or R [here β(R)]. These large rounded cells, showing red granules after Alcian blue-PAS staining, are mostly located in the median area of the anterior lobe, in the cystiform zone and in cell cords invading the neural lobe. In the fetal pituitary, reactivity is observed either in some differentiated β(R) cells or, earlier, in chromophobe cells.The question is now raised whether one cell may contain several peptides and, in this case, whether the different peptides are carried by the same granule. Technical procedures using numerous antisera on serial sections have shown associations at the level of a given cell (and of a given granule under the electron microscope). However, dissociations are also to be noticed, as far as ACTH and β-MSH (adult) and more particularly α-MSH (adult and fetus) are

ISSN:1663-2818    

DOI:10.1159/000179291

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The hypothalamic regulation of ACTH secretion has been reviewed. Recent biochemical investigations on corticotropin-releasing factor (CRF) suggest that CRF is present in the hypothalamus under two or more different molecular weight forms, their structure being not elucidated yet. Vasopressin has a CRF-like activity. However, contradictory results have been reported on the role of AVP as a physiological CRF. The synthesis of CRF appears to occur in a large hypothalamic area outside the median eminence. CRF-carrying fibers are thought to pass through the lateral retrochiasmatic area and project on the hypophysial portal vessels at the junction between the pituitary stalk and the median eminence. Conflicting data have been published on the influence of monoamines on ACTH secretion. In the dog, ACTH release is inhibited by the α-adrenergic receptors, this effect being not as clearly demonstrated in other species. The stimulation of nicotinic and muscarinic receptors is followed by increased ACTH secretion. Glucocorticoids appear to lower ACTH secretion through an action at both the hypothalamic and pituitary levels

ISSN:1663-2818    

DOI:10.1159/000179292

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The immunologic patterns of 3 human pituitary adenomas of Cushing’s disease have been studied after gel exclusion chromatography (Sephadex G-50). The immunologic characteristics were examined with three radioimmunoassays specific for human cor-ticotropin (ACTH). lipotropin (LPH) and β-endorphin (β-End). In cell tumor extracts, chromatographic peaks corresponding to β-LPH, γ-LPH, β-End and ACTH were identified. The ACTH/β-LPH-β-End ratio was 1 in the 3 cases. Additionally, in the 3 cases, a chromatographic peak, partially cross-reacting in the β-End assay, was eluted after β-End, thus suggesting the presence of a fragment of the molecule. In 1 case, a peak of large molecular weight material with N- and C-terminal β-LPH and ACTH immunoreactivity was observed, which corresponded to the precursor material.The release and the effects of various stimuli were studied on dispersed tumor cells in primary culture. The tumor cells had a biphasic basal secretion rate with a rapid increase of ACTH/β-LPH-β-End in the culture medium during the first 2 h. Then the release, studied during 2 days, was slower. Chromatographic studies showed that the β-LPH/β-End ratio was 0.8 in the cells and 0.3 in the medium, due essentially to the release of β-End and β-End-like materials. The cells released ACTH and β-LPH-β-End in equimolar ratio after stimulation with arginine vasopressin (AVP). The maximum effect was obtained with 10-6 M AVP (D50 = 1 10-9 M). Dibutyryl cyclic AMP (2 · 10-3 M) induced maximal release of ACTH/β-LPH-β-End. This stimulation was suppressed by a 48-hour preincubation with dexamethasone (10-8–10-6M). There was no effect of TRH and LH-RH on cell release. Dopamine (10-6M) specifically blocked the release of ACTH/β-LPH-β-End in 1 case. These data showed (a) heterogeneity of chromatographic profiles from case to case; (b) the presence of material in the tumor, cell extracts and culture medium corresponding to fragment(s) of β-End; (c) culture studies demonstrated that tumor cells remain responsive to AVP stimulation and dexamethasone suppression, and (d) the dopamine inhibition of ACTH and β-End release

ISSN:1663-2818    

DOI:10.1159/000179293

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Tissue from histologically confirmed ACTH cell adenomas in Cushing’s disease (CD) and Nelson’s syndrome (NS) was gained by transsphenoidal surgery. Combined enzymatic and mechanic agitation of tumor tissue yielded a cell suspension. Aliquots of the cell suspension were transferred to superfusion chambers immediately after isolation and investigated for ACTH and (3-endorphin production. Feedback action of cortisol (CO) and dexamethasone on basal hormone production and on lysine vasopressin (LVP) induced ACTH secretion were studied. Adenomatous tissue and anterior lobe tissue from the same patient in CD could be investigated simultaneously in 4 cases. The paraadenomatous tissue showed depression of basal and LVP-induced ACTH secretion. In all adenomatous tissues investigated there was missing or reduced suppression of basal ACTH secretion by physiological levels of CO. CO not only failed to suppress LVP-induced ACTH secretion but also seemed to enhance LVP stimulation in some experiments. This study confirms former results, that a missing or inversed feedback action of glucocorticoids in adenoma cells is a mechanism involved in the pathological ACTH secretion in CD and NS. Bioassayable and immunoreactive ACTH from media of superfusion and short-term static incubation were compared with β-endorphin and β-LPH in an assay detecting these two peptides with equimolar sensitivity. Secretory patterns were basically parallel but great differences showed in quantities of hormones secreted. In addition, Sephadex G-50 gel chromatography was performed to separate β-endorphin from β-LPH and to calculate the ratios. These profiles show great variations between different a

ISSN:1663-2818    

DOI:10.1159/000179294

出版商:S. Karger AG    

年代:1980

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000179295

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Studies in the experimental mouse pituitary tumor cell line AtT-20/D-16-v have recently shown that ACTH, the lipotropins (β- and γ-LPH), β-endorphin (β-End) and the 16-K fragment are synthesized through a common precursor molecule which is a 31,000 glycopeptide (pro-ACTH/endorphin). We have investigated whether such a biosynthetic model might exist in man. Radioimmunoassays have been developed against human ACTH, N-terminal LPH, β-End or C-terminal β-LPH, C-terminal γ-LPH, and the 16-K fragment or N-terminal pro-ACTH/endorphin. These radioimmunoassays were used to examine various human samples before and after gel fractionation in ordinary or denaturing buffers. Medium DMS-79, in which human small cell carcinoma cells derived from a lung cancer were cultured, was shown to contain molecules identical to γ-LPH, β-LPH, β-End and ACTH. In addition, it also contained a high molecular weight material with LPH, β-End, and ACTH immunoreactivity. These three immunoreactivities could not be dissociated under denaturing conditions (6 Mguanidine-HCl), and were all absorbed on an ACTH-purified anti-(l-24)-ACTH affinity column. Medium DMS-79 also contained high molecular weight calcitonin immunoreactivity that was not absorbed on the (1–24)-ACTH affinity column and therefore was not part of the pro-ACTH/endorphin molecule. Extracts from two pheochromocytomas responsible for the ectopic ACTH syndrome were found to contain, in addition to ACTH, large amounts of γ-LPH and β-End. High levels of β-LPH and β-End were also present in the plasma from a patient with the ectopic ACTH syndrome due to pancreatic carcinoma. Plasma immunoreactive 16-K fragment was increased in another patient with this syndrome. These results indicate that a biosynthetic model similar to that described in the AtT-20/D-16-v mouse tumor cell line also exists in man. Tumors responsible for the ectopic ACTH syndrome provide a unique source to study t

ISSN:1663-2818    

DOI:10.1159/000179296

出版商:S. Karger AG    

年代:1980

数据来源: Karger

ISSN:1663-2818    

DOI:10.1159/000179297

出版商:S. Karger AG    

年代:1980

数据来源: Karger