Pituitary beta-endorphin not involved in pain control in some pathophysiological conditions.
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Child↗
Biomedical subjects
X Bertagna
Publications and source records attributed to X Bertagna.
Simultaneous evaluation of the catecholamine pathway and three opioid peptide-producing systems in human pheochromocytomas.
Tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) activities, dopamine (DA), noradrenaline (NA), adrenaline (A), met 5-enkephalin (Met-Enk), leu5-enkephalin (Leu-Enk), dynorphin (Dyn) and beta-endorphin (beta-end) were measured simultaneously in ten human pheochromocytomas = 1 - TH activity was highly variable, from 22 to 2220 U/g tissue. 2 - DBH activity, in contrast, was rather constant, from 96 to 582 U/g. 3 - Catecholamines (A and NA) concentrations showed only small variations. 4 - The four opioid peptides were detected in all cases and exhibited a wide range of tissue concentrations (Enk much greater than Dyn greater than beta-end). 5 - Met-Enk and Leu-Enk concentrations were highly correlated; no correlation was observed with the other opioid peptides. 6 - A very strong correlation was observed between enkephalins concentrations and both catecholamines concentrations and DBH activities. These results are discussed in term of the significance of the co-localization of these various biologically active substances, principally with regard to the possible regulation of catecholamine synthesis by opioid peptides and conversely.
Adrenal Gland Neoplasms↗
Molecular forms of beta-endorphin in ACTH/LPH hypersecretion syndromes in man.
beta-Endorphin31, beta-endorphin1-27, and their alpha-N-acetyl derivatives were specifically separated by ion exchange chromatography from human beta-endorphin-'like' material obtained from extracts and culture media of corticotropic adenomas and extract of plasma from Nelson's syndrome and ectopic ACTH/LPH syndrome. Studies with pituitary-derived materials have shown that human beta-endorphin1-31 was the major form and human beta-endorphin1-27 a minor form. No other peptide was detected. In plasma from the ectopic ACTH-LPH syndrome human beta-endorphin1-31 was the only detected peptide. In 2 such patients with chronic elevation of human beta-endorphin1-31 the pain sensitivity threshold was normal and naloxone induced no modification, suggesting that circulatory human beta-endorphin has no effect on the central nervous system.
ACTH Syndrome, Ectopic↗
The new steroid analog RU 486 inhibits glucocorticoid action in man.
RU 486 [17 beta-hydroxy-11 beta-(4- dimethylaminophenyl )-17 alpha-(prop-1- ynyl )-estra-4,9-dien-3-one] is a new steroid analog which antagonizes glucocorticoid action at the receptor level in animals. To assess its potential antiglucocorticoid activity in man we studied the pituitary-adrenal response to RU 486 in normal men. The compound was administered at 0200 h and plasma cortisol and lipotropins (LPH) were measured hourly for 10 h. After 400 mg RU 486 significant and sustained elevation of both hormones occurred during the 0700-1200 h period: mean (+/- SE) plasma levels after placebo or RU 486 during this interval were, respectively, for cortisol (ng/ml), 63.4 +/- 8.2 and 112.7 +/- 2.9 (P less than 0.02); and for LPH (pg/ml), 34.8 +/- 11.3 and 71.6 +/- 15.4 (P less than 0.01). The 200- and 100-mg doses induced only transient cortisol and LPH increases. Administration of RU 486 (400 mg) at 1400 h induced no increase in plasma cortisol compared to placebo in the corresponding 2000 to 2400 h period. When RU 486 was administered concomitantly with dexamethasone (1 mg) at 2400 h, dose-dependent blockade of the dexamethasone-induced cortisol suppression at 0900 h was found (r = 0.62, P less than 0.01); this blockade was partial after the 100-mg dose, but complete after the 400-mg dose. Plasma LPH and ACTH showed parallel variations. We conclude that RU 486 antagonizes the negative pituitary feedback of both the nocturnal endogenous cortisol rise and exogenously administered dexamethasone. These actions are consistent with an antiglucocorticoid activity of this compound in man.
Adrenocorticotropic Hormone↗
Biochemistry of the hypothalamus in Parkinson's disease.
We assayed the content of neurotransmitters (or their synthesizing enzymes) and neuropeptides in the hypothalamus of control and parkinsonian brains post mortem. Only dopamine concentrations were lower than normal in Parkinson's disease, suggesting that deficiency in hypothalamic dopamine transmission may play a role in the autonomic and endocrine abnormalities of this disorder.
Aged↗
[Lipotropins (beta- and gamma-LPH). Valid indicators of corticotropic function].
Plasma levels of ACTH and LPH which derive from a common precursor, were determined simultaneously to study the value of LPH as a marker of the corticotropic function, and evaluate its advantage over that of ACTH plasma determination. ACTH and LPH plasma levels were measured: a) in control subjects under basal conditions and after dynamic explorations of the corticotropic axis. Furthermore, in some control subjects plasma LPH levels were measured after a 24 h incubation in blood at room temperature; b) in the venous and arterial blood of the kidney of subjects in whom a nephrectomy of a perfused and functional kidney was to be performed; c) in patients either under hemodialysis for chronic renal failure, or with adrenal insufficiency due to a primary adrenal failure or secondary to a corticotropic deficiency. This study permitted to establish: a) the normal values of basal plasma hormone levels (ACTH less than 10-80 pg/ml, LPH less than 20-200 pg/ml 8-9 a.m.) and to confirm their parallel secretions in physiological conditions; b) the stability of the LPH in blood at room temperature, whereas ACTH is rapidly destroyed in the same conditions; c) the primordial role of the kidney in the LPH catabolism; d) the value of LPH determinations in the diagnosis of primary adrenal insufficiency and corticotropic deficiency. Thus, except for the known situations where ACTH and LPH plasma levels are dissociated, the LPH plasma levels either basal or after dynamic explorations of the corticotropic axis, provide a reliable index of the corticotropic function.
Addison Disease↗
[Paraneoplastic hypercorticism].
Paraneoplasic hypercorticism results from ectopic corticolipotropic secretion. Its incidence remains underestimated because of the latent clinical forms of Cushing's disease. In some cases the primary tumour (bronchopulmonary, thymic, pancreatic or other) presents late. The variability of hormonal secretion makes it difficult to interpret dynamic tests. Measurement of ACTH and LPH are useful diagnostic aids; more specific markers of ectopic secretion have recently been reported. When the primary tumour cannot be directly treated, the quality of survival may be improved by the use of synthetic anticortisol drugs.
Adrenocortical Hyperfunction↗
[It has become possible to make hypophyseal adenomas regress by medical treatment].
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Adenoma↗
Peptides related to the NH2-terminal end of proopiocortin in man.
Peptides related to the NH2-terminus of proopiocortin in man were studied with three different RIAs directed toward gamma 3MSH, human 16K, and mouse 16K. The culture medium derived from a human corticotropic adenoma (SCH medium), which had previously been used as a human reference standard, generated competitive binding curves parallel to that of purified human 16K in all three RIA systems. Gel exclusion chromatography performed with pituitary-derived materials (adenoma extract and medium, and plasma from patients with Nelson's syndrome) showed that the overall immunoreactive gamma 3MSH eluted as one major peak at the position of human 16K. Its molecular weight estimated under denaturing conditions was 11,000. Gel exclusion chromatography performed with nonpituitary-derived materials (tumor extract and plasma from patient with the ectopic ACTH syndrome) showed that a major peak eluted at the position of human 16K, and a smaller molecular weight peptide eluted in a position intermediary between that of human 16K and synthetic gamma 3MSH. These data show that immunoreactive gamma 3MSH is indeed identical to human 16K in pituitary-derived materials. A different processing of the proopiocortin molecule is likely to occur in nonpituitary tumors and will result in the release of a smaller molecular weight peptide. The exact nature of this peptide is not known. It is speculated that it may serve as a nonpituitary tumor marker.
Adenoma↗
Plasma lipotropin increase in man after growth hormone administration. Comparison between extractive and biosynthetic hormones.
The action of human growth hormone (hGH) on plasma lipotropins (beta-and gamma-LPH) in 15 GH deficient patients was studied by comparing the effects induced by the acute administration of the extracted and biosynthetic molecules. The purified extracted preparation (6 mg/m2 im) induced a dramatic rise in plasma LPH: basal (49 +/- 12 pg/ml (mean +/- SEM); peak 1,658 +/- 262 pg/ml. The same dose of biosynthetic methionyl-hGH (met-hGH) induced no significant change in plasma LPH. Both preparations caused identical plasma GH increases. Six different commercially available extracted hGH preparations (Choay, France; Serono, Italy; France Hypophyse, France; Kabi, Sweden; Nordisk, Denmark; International Standard, Great Britain) all showed definite cross-reactivity in the LPH radioimmunoasay, varying from 0.1 to 1.0%, on a weight basis. No cross reactivity was found with met-hGH (less than 0.0001%). On gel exclusion chromatography, the LPH immunoreactivity of the purified preparations was dissociated from the GH immunoreactivity and eluted at the position of beta-and gamma-LPH. These data show that extracted hGH preparations are all contaminated with LPH and raise the question of the possible consequences of chronically elevated plasma LPH in treated patients. The use of biosynthetic met-hGH should prevent this occurence.
Adolescent↗
Responses of isolated guinea-pig adrenal cells to ACTH and pro-opiocortin-derived peptides.
A comparison of the responses of isolated guinea-pig adrenal cells to ACTH and pro-opiocortin-derived peptides was carried out by measuring cortisol, aldosterone, androstenedione and dehydroepiandrosterone production. With concentrations below 10,000 pg/ml, no steroidogenic activity was found in response to either beta-LPH, gamma-LPH, gamma 3-MSH or the 16K fragment, whether assayed alone or in association with ACTH. At concentrations above 10,000 pg/ml, gamma-LPH (100 ng), the 16K fragment (100 ng) and beta-endorphin (500 ng) proved to be totally inactive. beta-LPH from 25 to 250 ng, however, exhibited a significant though slight stimulatory effect on cortisol, aldosterone and androstenedione production. Its effectiveness on aldosterone production was especially marked, but the extent of the response was modest in view of the concentrations used.
Adrenal Glands↗
Simultaneous measurement of beta-endorphin, lipotrophins and met-enkephalin in phaeochromocytomas.
Tissue concentrations of immunoreactive lipotrophin, beta-endorphin, and met-enkephalin were determined in 10 phaeochromocytomas, 3 of which were responsible for the ectopic ACTH syndrome. Lipotrophin and beta-endorphin immunoreactivities could be detected in all cases, whether or not Cushing's syndrome was present, and their tissue concentrations were significantly correlated (r = 0.95, P less than 0.001). Chromatographic studies showed that gamma-lipotrophin and beta-endorphin were the main peptides in the tumours. Met-enkephalin immunoreactivity was also found in all tumours examined, at much higher concentration and showing no correlation with either lipotrophin or beta-endorphin immunoreactivity. Although beta-endorphin and met-enkephalin are thought to originate from different precursor molecules, these data show that the two opioid peptides may be secreted by the same tumour. The evidence for excess secretion of opioid peptides and their pathological significance in phaeochromocytomas remain to be established.
Adolescent↗
[Application of hormone determination to the diagnosis of pituitary corticotropic adenomas].
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Adenoma↗
[ACTH, beta-endorphin, lipotropins, and other pro-opiocortin-derived peptides: a new family of hormones (author's transl)].
beta-Endorphin, a pituitary morphino-mimetic peptide, was identified in a culture medium derived from a human corticotropic adenoma. Secretion products from cultured human cells derived from a small-cell carcinoma of the lung were shown to contain a high molecular weight precursor analagous to pro-opiocortin: this molecule is a polypeptide of the order of 28,000 daltons the enzymatic processing of which leads to the coordinated and simultaneous release of different peptide fragments: ACTH, beta- and gamma-lipotropins, beta-endorphin, fragment 16 K and gamma 3-MSH. All these peptides have been identified in human plasma, and pituitary and non-pituitary tumor extracts. Their plasma concentrations vary in a parallel manner, beta-endorphin and a peptide very similar to beta-MSH have been detected in human hypothalamus.
Adenoma↗
[Ectopic secretion of ACTH and of related peptides (LPHs, beta-endorphin, "16K"). Evidence for a common precursor].
Studies in the experimental mouse pituitary tumor cell line AtT-20/D-16-v have recently shown that ACTH, the lipotropins (beta- and gamma-LPH), beta-endorphin (beta-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, beta-End or C-terminal beta-LPH, C-terminal gamma-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 gamma-LPH, beta-LPH, beta-End and ACTH. In addition, it also contained a high molecular weight material with LPH, beta-End, and ACTH immunoreactivity. These three immunoreactivities could not be dissociated under denaturing conditions (6 M guanidine-HCl), and were all absorbed on an ACTH-purified anti-(1-24)-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 gamma-LPH and beta-End. High levels of beta-LPH and beta-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 this model in man.
Adrenocorticotropic Hormone↗
Evidence for a peptide similar to 16K fragment in man. Its relationship to ACTH.
A radioimmunoassay directed toward the NH2-terminal region of mouse pro-ACTH/endorphin (called 16K fragment) was used to examine human samples. Culture media from two corticotropic adenomas and plasmas from 11 patients with various ACTH hypersecretory syndromes gave parallel displacement curves; displacement curves for human samples were not parallel to purified mouse 16K fragment. Following sodium dodecyl sulfate polyacrylamide gel electrophoresis of culture medium from one adenoma, a major peak of 16K fragment immunoreactivity with an apparent molecular weight of ca. 16,000 was detected. A significant correlation (r = 0.963 ; p less than 0.001) was found between immunoreactive 16K fragment and ACTH in the patients' plasmas. These data indicate that a peptide similar to 16K fragment exists in man ; that human and mouse 16K fragment are immunologically distinguishable and that human 16K fragment appears to be secreted concomitantly with ACTH.
Addison Disease↗
Characterization of lipotropin-, corticotropin-, and beta-endorphin-immunoreactive materials secreted in vitro by a human pituitary adenoma responsible for a case of Nelson's syndrome.
A human pituitary adenoma responsible for a case of Nelson's syndrome was maintained in organ culture and the incubation medium was examined with four different RIAs; human corticotropin (ACTH), beta-MSH, lipotropin (LPH), and beta-endorphin (beta-End). All four immunoreactivites (IRs) were present in the medium obtained after 24 h of incubation. Gel exclusion chromatography under denaturing conditions (6 m guanidine HCl) revealed several immunoreactive components. Two components having both human beta-MSH (beta-hMSH) and human LPH (hLPH) IR coeluted with beta-hLPH and gamma-hLPH; a component with beta-hMSH IR but no hLPH IR coeluted with [125I]beta-hMSH; a component with human ACTH (hACTH) IR eluted at the position of hACTH. Sephadex G-50 gel exclusion chromatography revealed that approximately 80% and 20% of human beta-End (beta-hEnd) IR were accounted for by components coeluting with beta-hLPH and beta-hEnd, respectively. These data demonstrate the presence in this incubation medium of materials similar to if not identical with beta-hLPH, gamma-hLPH, hACTH, beta-hMSH, and beta-hEnd; they suggest that all of these peptides may be secreted in the circulation of patients with Nelson's syndrome.
Adenoma↗
Immunoreactive beta-MSH in human plasma and in a corticotrophic adenoma culture medium. Its relation to the lipotrophins.
In order to characterize more accurately the relationship between immunoreactive beta-MSH ("BETA-MSH") and the lipotrophins (LPH) we attempted to investigate the gel filtration and the immunological characteristics of "beta-MSH" in the plasma of patients with Nelson's syndrome and Addison's disease as well as in the culture medium from a human corticotrophic adenoma using a sensitive radioimmunoassay from human beta-MSH. When added either to hormone free plasma or to a plasma from a patient with Nelson's syndrome all the human beta-MSH (hbeta-MSH) elutes from a Sephadex G-50 column as a single peak in a volume corresponding to its molecular weight. In contrast plasma "beta-MSH" in 3 patients with Nelson's syndrome and one patient with Addison's disease almost completely elutes in a volume corresponding to a molecular weight range of 6000-10 000; no "beta-MSH" can be detected in its normal elution volume. Drastic pH change (8.2 to 2.3) does not significantly alter the elution pattern. Chromatography of a corticotrophic adenoma culture medium gave a similar pattern of "beta-MSH" with a main peak in the molecular weight range of 6000-10 000. In our radioimmunoassay the culture medium and purified hbeta-LPH gave parallel displacement curves for [125I]hbeta-MSH. It is suggested that hbeta-LPH or a closely related substance is the main material responsible for "beta-MSH" immunoactivity.
Addison Disease↗