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Biomedical subjects

J Hope

Publications and source records attributed to J Hope.

At least 109 records · Page 6Linked to original sources
PubMed1983

Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours.

Basal and stimulated secretion of N-terminal pro-opiocortin (Pro-gamma-MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel-chromatographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1-39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.

ACTH Syndrome, Ectopic↗
PubMed1981

Circulating human pituitary pro-gamma-melanotropin enhances the adrenal response to ACTH.

The amino-terminal region of the common corticotropin/beta-lipotrophin (beta-LPH) precursor has been identified in the AtT-20 mouse tumor cells as a glycopeptide with an apparent molecular weight of 16,000 (the '16K fragment'). A third melanotropin core sequence or gamma-MSH similar to that found in ACTH and beta-LPH was predicted to occur in this glycopeptide from the complementary DNA sequence of mRNA isolated from bovine pituitary intermediate tissue. Recently, the mouse of 16K fragment has been found to have a small but significant potentiation on the corticosteroidogenesis elicited by ACTH in a static cell system, an effect that could be enhanced when the glycopeptide was pretreated with trypsin. This synergism could also be mimicked by synthetic gamma-MSH peptides in vitro and in vivo. We report here the potentiating properties of a naturally occurring human pro-gamma-MSH glycopeptide on the ACTH-induced steroidogenic response of isolated perfused rat and human adrenocortical cells.

Adrenal Cortex↗
PubMed1981

Pars intermedia peptides: studies in adult humans.

A combination of radioimmunoassays and chromatography under acid-dissociating conditions has been used to obtain profiles of ACTH and LPH-related peptides in human plasma and cerebrospinal fluid. The spectra of peptides observed in these two fluids differ markedly. ACTH, beta-LPH, gamma-LPH and beta-endorphin are observed in the plasma of normal subjects and patients with increased pituitary ACTH secretion, whereas cerebrospinal fluid contains ACTH, beta-LPH, gamma-LPH and beta-endorphin, a 31 000-molecular-weight putative precursor having ACTH, LPH and gamma-MSH immunoreactivities, as well as pro-gamma-MSH(1-77) and smaller immunoreactive gamma-MSH fragments, alpha-MSH was not observed in blood or cerebrospinal fluid but this pars intermedia peptide and corticotropin-like intermediate lobe peptide (CLIP) were both found in tumour tissues obtained from patients with the ectopic ACTH syndrome. In vitro studies of human pituitary tumour tissues confirmed concomitant secretion of ACTH, beta-LPH, gamma-LPH, beta-endorphin and pro-gamma-MSH, which could be stimulated by a preparation of crude stalk median eminence and synthetic arginine vasopressin, from the rat, and could be suppressed by hydrocortisone. Clinical studies in which electroacupuncture was used to alleviate the symptoms of heroin withdrawal or recurrent pain revealed that concentrations of met-enkephalin and beta-endorphin, respectively, may rise in cerebrospinal fluid in association with relief of symptoms.

Adrenocorticotropic Hormone↗
PubMed1981

Nature and control of peptide release from the pars intermedia.

Pro-opiocortin, the precursor of ACTH, LPH and gamma-MSH, is biosynthesized in both the cells of the pars intermedia and the corticotrophs of the pars distalis. In the pars distalis its processing does not vary significantly from species to species whereas in the pars intermedia large differences occur. The release of ACTH, beta-LPH and pro-gamma-MSH from the corticotrophs is under common positive control by hypothalamic corticotropin-releasing factor (CRF) and the nature of the peptides remains unchanged when they are secreted. The release of all five pars intermedia peptides that we have measured in vitro appears to be under tonic dopaminergic inhibition. The secreted peptides have also been identified chromatographically. The lack of unequivocal physiological function in the periphery, the diversity of the pars intermedia peptides and this common control mechanism tend to preclude a simple endocrine role for the pars intermedia. The neural effects of MSH and endorphin are well documented and specific neuronal uptake therefore cannot by dismissed. The absence of pars intermedia in the adult human pituitary suggests that such a site of synthesis of these peptides plays a minor role in learning and behaviour in a species (such as Homo sapiens) that has a highly evolved intelligence and may, instead, need to synthesize the peptides only in the brain.

Adrenocorticotropic Hormone↗
PubMed1981

Purification and characterization of amino-terminal pro-opiocortin peptides from human pituitary glands.

Two cystine-containing peptides isolated from human pituitaries were partially sequenced. The peptides are fragments derived from the amino-terminal of pro-opiocortin (NPOC) and have been chemically characterized as NPOC 1-28 (which lacks gamma-MSH) and NPOC 2-59. Their availability enables us to investigate new putative biological roles for the amino-terminal conserved sequence of pro-opiocortin.

Amino Acid Sequence↗
PubMed1981

Development of a radioimmunoassay for an amino-terminal peptide of pro-opiocortin containing the gamma-MSH region: measurement and characterization in human plasma.

A radioimmunoassay has been developed for the N-terminal region of human pituitary pro-opiocortin (N-POC), the common precursor protein of ACTH and beta-LPH, using an antiserum which recognizes residues near the gamma-MSH region. The concentrations of greater than 300 ng/l of immunoreactive peptide were determined in unextracted human plasma, the relative molecular mass of the reacting fragments corresponding to a seventy-seven amino acid glycoprotein. The concentrations of immunoreactive N-POC peptides were correlated with those of ACTH in plasma obtained from patients with various disorders of the hypothalamic-pituitary-adrenal axis.

ACTH Syndrome, Ectopic↗
PubMed1981

Characterisation of the pro opiocortin family of peptides in human cerebrospinal fluid.

Chromatography under acid dissociating conditions in conjunction with radioimmunoassay has been employed to investigate the nature of peptides related to opiocortin in human cerebrospinal fluid. Samples of cerebrospinal fluid (CSF) were collected for chromatography from 15 patients prior to air encephalography. 2 patients had pituitary dependent Cushing's disease, 3 non-endocrine neurological disease and 10 non-ACTH related pituitary disease. The column fractions were assayed for N- and C-terminal beta-lipotropin, N-terminal ACTH and gamma-MSH immunoreactivity. Elution profiles obtained from chromatography on Sephadex G-50 demonstrated peaks of immunoreactivity corresponding to the elution positions of synthetic human beta-endorphin, highly purified beta-lipotropin and highly purified gamma-lipotropin in all CSF samples. A peak of a large molecular weight material with N and C terminal beta-lipotropin immunoreactivity was also detected. Chromatography of CSF on Sephadex G-75 showed this large molecular weight peak to be comprised of peptides eluting in the positions of a 31K molecular weight marker with beta-lipotropin and ACTH immunoreactivity and a 16K molecular weight marker with gamma-MSH immunoreactivity. This suggests the presence of the common precursor to ACTH and LPH in the CSF.

Chromatography, Gel↗
PubMed1980

Purification and characterization of a gamma-melanotropin precursor from frozen human pituitary glands.

A new melanocyte-stimulating peptide has been isolated from acid extracts of frozen human pituitary glands by salt/ethanol fractionation, Sephadex G-75 gel filtration and DEAE- and cM-cellulose ion-exchange chromatography. The peptide is glycosylated, has an N-terminal tryptophan residue and an apparent mol.wt. of 16000 as estimated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Its amino acid analysis closely resembles residues Trp-105 to Gln-29 predicted for the common precursor protein of bovine corticotropin and beta-lipotropin by Nakanishi, Inoue, Kita, Nakamura, Chang, Cohen & Numa [(1979) Nature (London) 278, 423-427]. This fragment is expected to have melanotropin activity due to the tetrapeptide -His-Phe-Arg-Trp- (residues -51 to -48) of the predicted sequence of the common precursor. It was found to have a molar potency of 1 X 10(-5) relative to alpha-melanotropin in the frog skin bioassay. These characteristics are consistent with the isolated melanotropin peptide being a non-corticotropin, non-lipotropin peptide of the human common precursor protein of corticotropin and lipotropin. The peptide neither potentiates the adrenal weight-maintenance activity of corticotropin-(1-24)-tetracosapeptide when administered to hypophysectomized rats, nor stimulates release of non-esterified fatty acids from isolated rat epididymal cells. A second N-terminal-tryptophan glycopeptide was also isolated, which had an amino-acid composition similar to that predicted for the bovine common precursor protein, residues Trp-105 to Gly-35.

Amino Acids↗
PubMed1979

Adrenocorticotrophin-related peptides in adult and foetal sheep pituitary glands.

Differences in foetal and adult adrenal function may be due to qualitative as well as quantitative changes in the pituitary corticotrophic stimulus. Pituitary glands from adult and foetal sheep were freshly dissected and stored at -70 degrees C until extracted at pH 1.5. The extracts were subjected to chromatography on Sephadex G-100 superfine and fractions were assayed by multiple radioimmunoassays directed against the NH2- and CO2H-terminal sequences of ACTH and lipotrophin (LPH). Peaks corresponding to beta-melanocyte-stimulating hormone (beta-MSH), beta-LHP, gamma-LPH, beta-endorphin and ACTH were identified, with little or no evidence for the presence of alpha-MSH and corticotrophin-like intermediate lobe peptide. Three peaks of large molecular weight material, A. B and C, were identified and their relative proportions shown to be considerably greater in the foetus than in the adult. The immunoassay profile of peaks A and B suggested that they were 'stem hormones' which could give rise to a family of biologically active peptides. Since the 'family tree' which they engender varies according to the stage of development, it is proposed that the changes in the 'trophic family' may explain the different adrenal responses of the foetal and adult sheep.

Adrenocorticotropic Hormone↗
PubMed1978

beta-Endorphin in human cerebrospinal fluid.

beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinal fluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary.

Adult↗