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Biomedical subjects

J Rivier

Publications and source records attributed to J Rivier.

At least 271 records · Page 15Linked to original sources
PubMed1983

Corticotropin releasing factor produces increases in brain excitability and convulsive seizures in rats.

Corticotropin releasing factor (CRF) is a 41-residue peptide, capable of stimulating the secretion of corticotropin (ACTH)-like and beta-endorphin-like immunoreactivity from the adenohypophysis. Low doses of CRF (0.0015-0.15 nM) given intracerebroventricularly (i.c.v.) produced changes in electrographic activity suggestive of increased arousal. Higher doses of CRF (1.5-3.75 nM) induced, over a period of 3-7 h, electrographic and behavioral signs of seizure activity indistinguishable from those which occur following electrical 'kindling' of the amygdala.

Animals↗
PubMed1983

Sequence analysis of rat hypothalamic corticotropin-releasing factor with the o-phthalaldehyde strategy.

Sequence analysis was performed on a 41-residue polypeptide that has been identified as the predominant form of high intrinsic corticotropin-releasing activity of rat hypothalamus. The sequence of residues 1-39 of this corticotropin-releasing factor (CRF) was determined by Edman degradation of a partially purified peptide in a highly sensitive spinning cup sequencer after selective blocking of CRF or its main contaminant with o-phthalaldehyde. This approach was validated by peptide mapping of CRF of a highly purified preparation. Peptide mapping was accomplished with reverse-phase high-pressure liquid chromatography of CRF fragments obtained by digestion with clostripain. The identities of the fragments cleaved from CRF were established by chromatographic comparison with synthetic peptides, amino acid analysis, and Edman degradation. On the basis of these experiments, the primary structure of rat hypothalamic CRF was established to be H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu- Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn - Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. It is expected that the o-phthalaldehyde strategy will facilitate the sequence analysis of partially purified peptides containing proline residues.

Amino Acid Sequence↗
PubMed1983

Corticotropin releasing factor decreases postburst hyperpolarizations and excites hippocampal neurons.

Corticotropin releasing factor in concentrations of 15 to 250 nanomoles per liter increased the spontaneous discharge frequency and decreased the size of hyperpolarizations after burst discharges in CA1 and CA3 pyramidal neurons of rat hippocampal slices. Concentrations greater than 250 nanomoles per liter also depolarized the cells. These excitatory actions of corticotropin releasing factor may involve a novel calcium-dependent process.

Action Potentials↗
PubMed1983

Effects of human pancreatic tumour growth hormone releasing factor on growth hormone and somatomedin C levels in patients with idiopathic growth hormone deficiency.

Human pancreatic tumour growth hormone releasing factor (hpGRF-40) 10 micrograms/kg was administered intravenously to 6 normal young men and 12 adult patients who had presented in childhood with growth hormone (GH) deficiency (7 patients had isolated GH deficiency, 4 had multiple anterior pituitary hormone deficiencies, and 1 had Hand-Schüller-Christian [HSC] disease). hpGRF-40 administration increased serum GH concentrations in all normal subjects and in 3 of 7 patients with isolated GH deficiency and in the 1 with HSC disease; however, the mean serum GH concentration in the patients who responded was less than that of the normal subjects. Somatomedin C concentrations were increased 24 h after a single dose of hpGRF-40 in 8 of 10 patients with GH deficiency. All subjects experienced flushing in response to hpGRF-40. A patient with isolated GH deficiency received 0.33 micrograms/kg hpGRF-40 every 3 h for 5 days. Despite the modest increase in GH in response to a subsequent dose of 10 micrograms/kg hpGRF-40, serum somatomedin C levels increased within 12 h from 0.06 to 0.1 U/ml and peaked at 0.36 U/ml at 72 h; in addition the patient with HSC disease, treated with hpGRF-40 daily for 5 days, demonstrated an increase in somatomedin C from 0.4 to 0.58 U/ml. The increase after hpGRF-40 in serum GH levels in this patient and the similar or greater responses in 3 of 7 patients suggest that at least some of these patients may have hypothalamic GH-releasing-hormone deficiency. hpGRF-40 may be useful in distinguishing pituitary disease from hypothalamic disease. After hpGRF-40 administration serum somatomedin C levels may increase without a change in serum immunoreactive GH concentrations. Further studies are needed to determine whether hpGRF-40 is useful in promoting linear growth in children with GH deficiency.

Adult↗
PubMed1983

Synthetic corticotropin-releasing factor stimulates secretion of immunoreactive beta-endorphin/beta-lipotropin and ACTH by human fetal pituitaries in vitro.

Synthetic ovine CRF, in an amount approximating that found in pituitary portal plasma of the rat, induced a significant increase in the secretion of both ACTH and immunoreactive beta-endorphin/beta-LPH (i beta-END/LPH) by human fetal hemipituitaries in an in vitro superfusion system. This finding suggests that a molecule similar to synthetic ovine CRF may be a physiologic hypothalamic releasing factor in man.

Adrenocorticotropic Hormone↗
PubMed1983

Human pancreatic growth-hormone-releasing factor selectively stimulates growth-hormone secretion in man.

A growth-hormone-releasing factor has been characterised and sequenced from a pancreatic tumour removed from a patient with acromegaly. It is a 40-residue linear peptide. Synthetic human pancreatic growth-hormone-releasing factor (hpGRF-40), 1 microgram/kg bodyweight, was administered as an intravenous bolus to six healthy men. hpGRF-40 selectively stimulated growth-hormone secretion. Serum growth-hormone concentrations were increased within 5 min, reaching a peak between 30 and 60 min (20 . 4 +/- 6 . 5 ng/ml compared with 2 . 1 +/- 0 . 1 ng/ml after placebo). Serum levels of prolactin, thyrotropin, luteinising hormone, and corticotropin (measured indirectly through plasma cortisol) were not increased after administration of hpGRF-40. Similarly, the concentrations of blood glucose, plasma insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, and somatostatin were unaffected by hpGRF-40. There were no changes in blood pressure, pulse rate, or body temperature, and no side-effects were noted. The characteristics of this peptide fulfil many of the criteria required of the hypophysiotropic growth-hormone-releasing hormone. hpGRF holds promise for a new approach to the diagnosis and treatment of various disorders of growth-hormone secretion.

Acromegaly↗
PubMed1983

In vitro and in vivo ACTH-releasing activity of ovine CRF, sauvagine and urotensin I.

The ability of three homologous peptides, ovine corticotropin-releasing factor (CRF), sauvagine and urotensin I, to release ACTH was examined in vitro and in vivo. All three peptides exhibit statistically equivalent potencies to stimulate ACTH secretion both by cultured pituitary cells and in pharmacology blocked rats. These results suggest that all three peptides evolved from a common mammalian precursor that possessed high hypophysiotropic potency.

Adrenocorticotropic Hormone↗
PubMed1983

Flow cytometric separation of gonadotrophs from dispersed rat pituitaries using a fluorescent GnRH antagonist.

A gonadotropin-releasing hormone (GnRH) antagonist, [Ac-delta 3 Pro1,pFDPhe2,DTrp3,DLys6[-GnRH, was synthesized, conjugated to tetramethyl rhodamine, and found to retain GnRH antagonist activity. The fluorescent compound was used to label dispersed pituitary cells from 14-17 day-old Sprague-Dawley female rats. A subset comprising approximately 10% of the pituitary population was specifically labeled with a mean intensity of fluorescence 4.9-fold higher than the unlabeled population. The labeled cells were larger on average than the general population as inferred by forward narrow angle light scatter intensity measurements, and more granular as inferred by right angle light scatter intensity. Cells were sorted on the basis of fluorescent intensity: gonadotrophs were found to be concentrated in the rhodamine-positive fraction 5- or 6-fold relative to unfractionated cells, and 21- or 28-fold relative to rhodamine-negative fraction cells based on LH or FSH content, respectively. Gonadotrophs comprised 73 +/- 3.9% of the rhodamine-positive fraction by immunocytochemical staining. Sorted rhodamine-positive cells were cultured and found to be fully functional with respect to subsequent challenge with 30 nM GnRH. We conclude that the use of the fluorescent GnRH antagonist in conjunction with a multi-parameter cell sorter allows the purification of gonadotrophs, indicating, as expected, that these cells have a significantly higher level of GnRH binding sites than the general pituitary population. This technology should prove generally valuable in endocrine research.

Animals↗
PubMed1983

Conformation of somatostatin using scalar coupling constants from 270 and 600 MHz simulated proton magnetic resonance spectra.

The conformation of the 14 amino acid peptide hormone somatostatin in aqueous solution was investigated through a proton magnetic resonance (PMR) scalar coupling analysis. Experiments were performed at two fields, 270 and 600 MHz, and included double and triple resonance difference scalar decoupling, resolution enhancement and computer simulation. The agreement between simulated and observed spectra at both fields provided support for the correctness of the analysis. The resultant scalar coupling constants, 3J alpha H-NH and 3J alpha B, gave information on the backbone (phi) and side chain (chi 1) torsional angles, respectively, which eliminated either of the proposed conformations of somatostatin as describing a predominant conformer of the molecule in solution under our conditions.

Magnetic Resonance Spectroscopy↗
PubMed1983

Characterization of rat hypothalamic corticotropin-releasing factor.

A polypeptide was purified from rat hypothalamic extracts on the basis of its high intrinsic activity to release corticotropin (ACTH) from cultured rat anterior pituitary cells and its immunoactivity in a radioimmunoassay directed against the NH2 terminus (residues 4-20) of ovine hypothalamic corticotropin-releasing factor (CRF). Based on Edman degradation, peptide mapping, and amino acid analysis, the primary structure of this rat CRF was established to be: H-Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys-Leu-Met-Glu-Ile-Ile-NH2. The hypophysiotropic potency of synthetic rat CRF did not deviate significantly from the potencies of the isolated native peptide or of synthetic ovine CRF. The close structural relationship between rat and ovine hypothalamic CRF is indicated by an 83% sequence homology.

Amino Acid Sequence↗
PubMed1983

Structural homology of corticotropin-releasing factor, sauvagine, and urotensin I: circular dichroism and prediction studies.

Three recently isolated peptides, whose sequences have been determined--the corticotropin (adrenocorticotropic hormone)-releasing factor of ovine origin, sauvagine, from the skin of the frog Phyllomedusa sauvagei, and urotensin I from the teleost fish, Catostomus commersoni--show high (greater than 50%) sequence homology. CD spectra of the three peptides in trifluoroethanol indicate predominantly helical character for these peptides. Analysis of the secondary structures by the Chou-Fasman method predicts that the overall structural organization of the peptides is the same. All three possess a long internal helix, spanning about 25 residues, connected by a turn region to a COOH-terminal structural element that is an alpha-helix in corticotropin-releasing factor and urotensin I and a beta-sheet in sauvagine. The values for helical content estimated from the prediction method agree reasonably well with those computed from the CD spectra. This agreement as well as the CD spectra of corticotropin-releasing factor fragment 5-33 support the specific assignments of helical regions derived from the Chou-Fasman analysis. The three peptides exhibit significantly less helical structure in water than in trifluoroethanol as indicated by CD spectra. Hydrophilicity profiles provided comparison of the three peptides in terms of their overall hydrophilicity and the location of the regions of maximal hydrophilicity. A unique distribution of hydrophilic and hydrophobic residues within the internal helices is revealed by helical wheel analysis. Patches of both types of residues are formed following a heptad (four/three) rule. Since the two patches are shifted by one residue relative to one another, together they occupy only one face of the helical surface, a feature distinct from other amphiphilic structures.

Amphibian Proteins↗
PubMed1983

Surface properties of an amphiphilic peptide hormone and of its analog: corticotropin-releasing factor and sauvagine.

Synthetic corticotropin (adrenocorticotropic hormone)-releasing factor [CRF; for the sequence, see Vale, W., Spiess, J., Rivier, C. & Rivier, J. (1981) Science 213, 1394-1397] in aqueous solution exists predominantly as a random coil. At concentrations greater than 1 microM, the peptide shows a tendency to self-aggregate with a concurrent slight increase in the apparent alpha-helical content as measured by the CD spectrum. The alpha-helix formed by this molecule is highly amphiphilic--i.e., the hydrophilic and hydrophobic regions are segregated on opposite faces of the helix. As predicted from the potential amphiphilic structure, CRF binds avidly to the surface of single bilayer egg phosphatidylcholine vesicles. This binding appears to obey a simple Langmuir isotherm with the following parameters: Kd = 1.3 +/- 0.6 X 10(-7) M and capacity at saturation (N) = 11.0 +/- 1.0 mmol of peptide per mol of phospholipid. CRF also readily forms an insoluble monolayer at the air-water interface. The monolayer is composed of monomers of the hormone with molecular areas, A'0 = 22 A2 per amino acid, suggesting a compact secondary structure. Judged from the collapse pressure (19.0 +/- 0.1 dyne/cm; 1 dyne = 10 microN) of the monolayer, the amphiphilicity of CRF approximates that of plasma apolipoproteins, a class of proteins of the most pronounced amphiphilic character. These results suggest that the binding of CRF to the cell membrane is accompanied by the induction of an alpha-helical secondary structure and it is this predominantly helical form that is the biologically active form of the peptide.

Amino Acid Sequence↗
PubMed1983

Characterization of a teleost gonadotropin-releasing hormone.

A peptide that is recognized by certain antibodies raised against mammalian gonadotropin-releasing hormone has been purified from extracts of salmon brains by gel filtration and high-performance liquid chromatography. The primary structure of this 10-residue peptide is less than Glu-His-Trp-Ser-Tyr-Gly-Trp-Leu-Pro-Gly-NH2. This represents a difference of two amino acids between salmon and mammalian gonadotropin-releasing hormone and demonstrates that most of the molecule has been conserved during evolution. The synthetic form of salmon gonadotropin-releasing hormone is less potent than is mammalian gonadotropin-releasing hormone on mammalian cells and is biologically active in salmon.

Amino Acid Sequence↗