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Biomedical subjects

J Rivier

Publications and source records attributed to J Rivier.

At least 307 records · Page 17Linked to original sources
PubMed1983

Plasma distribution, disappearance half-time, metabolic clearance rate, and degradation of synthetic ovine corticotropin-releasing factor in man.

The plasma distribution, disappearance half-time, MCR, and degradation of corticotropin-releasing factor (CRF) were studied in normal men who received a pulse injection of synthetic ovine CRF (oCRF). Graded iv doses of oCRF produced a linear increase in plasma immunoreactive oCRF (IR-oCRF). The calculated total plasma content of IR-oCRF 2 min after injection represented 41.7 +/- 2.5% (mean +/- SE) of the injected dose. The disappearance of IR-oCRF from plasma was characterized by a biexponential decay curve, with initial distribution and subsequent metabolic t 1/2 values of 6.1 +/- 0.5 and 55 +/- 3.8 min (mean +/- SE), respectively. In two subjects who were studied for 14-16 h after being given the largest dose of oCRF, there was third phase of disappearance, with a t 1/2 of 198 +/- 54 min. The MCR of IR-oCRF was 2.4 +/- 0.2 ml/min . kg (146 +/- 12 l/m2 . day) and was relatively constant over a 3000-fold dose range. The volume of distribution of IR-oCRF was 6.2 +/- 0.6 liters. The plasma IR-oCRF component, examined at increasing intervals after injection, was indistinguishable from the injected oCRF in that its apparent molecular size had not been altered, nor had its biological activity been attenuated. The continued circulation of apparently intact, biologically active oCRF for at least 90 min after injection was associated with sustained release of ACTH into the plasma. Thus, the clearance of oCRF from circulating human plasma is prolonged and appears to be responsible for the sustained release of ACTH that occurs after injection of this hormone-releasing factor.

Adrenocorticotropic Hormone↗
PubMed1983

Hormonal effects of danazol and medical oophorectomy in endometriosis.

The hormonal effects of danazol and of a long-acting gonadotropin-releasing hormone analogue (GnRH-a) were studied in women with endometriosis and those with oophorectomy. During danazol treatment, total serum concentrations of estrone and estradiol, and free, dialyzable estradiol were reduced to the low follicular phase range for premenopausal women. Corresponding estrogen levels were suppressed to a significantly greater degree (P less than .02) at the end of GnRH-a administration, to concentrations which were twofold to fourfold lower than with danazol therapy and similar to values in the oophorectomized women. Sex hormone binding globulin was markedly suppressed (P less than .001) throughout danazol treatment, resulting in a threefold elevation (P less than .01) of free testosterone. These data suggest that danazol may affect endometriosis by mechanisms other than by inducing a pseudomenopause. The increased tissue availability of testosterone may be responsible for acne and hirsutism observed in some women during danazol treatment and may inhibit proliferation of the ectopic endometrium. Medical oophorectomy using GnRH-a may have improved effects on endometriosis without the androgenic side effects of danazol.

Castration↗
PubMed1982

Sequence analysis of a growth hormone releasing factor from a human pancreatic islet tumor.

A growth hormone releasing factor of a human pancreatic islet tumor (hpGRF) of an acromegalic patient was purified and subjected to Edman degradation in a spinning cup sequencer. Approximately 0.7-1.2 nmol of peptide was applied to the cup without any pretreatment, after coupling to 3-sulfophenyl isothiocyanate or after cleavage with cyanogen bromide, staphylococcal protease, or trypsin. On the basis of the analytical data, the N-terminal sequence of 39 residues is established to be H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn- Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys- Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser- Asn-Gln-Glu-Arg-Gly-. It is proposed that alanine is residue 40 and represents (as free acid) the C terminus of hpGRF. Synthetic hpGRF(1-40)-OH is highly potent in stimulating GH secretion from the rat anterior pituitary in vitro and in vivo. The C-terminal sequence of hpGRF does not appear to contribute significantly to the biologic intrinsic activity and potency of hpGRF, as demonstrated by the fact that the natural product and the synthetic peptides hpGRF(1-40)-OH, hpGRF(1-40)-NH2, and hpGRF(1-29)-NH2 show equivalent in vitro activities. On the basis of sequence homologies, hpGRF is closely related to members of the glucagon secretin family, especially to the porcine gut peptide PHI.

Adenoma, Islet Cell↗
PubMed1982

Inhibition of adrenocorticotropic hormone secretion in the rat by immunoneutralization of corticotropin-releasing factor.

Intravenous administration of rabbit antiserum to ovine corticotropin-releasing factor (CRF) markedly reduced the CRF-induced rise of plasma adrenocorticotropic hormone (ACTH) in intact nonstressed adult male rats while blocking more than 75 percent of the ACTH release observed in rats exposed to ether stress. Furthermore, antiserum to CRF significantly lowered ACTH levels in adrenalectomized animals. These results suggest that endogenous CRF plays a physiological role in regulating ACTH secretion.

Adrenalectomy↗
PubMed1982

Intraventricular corticotropin-releasing factor enhances behavioral effects of novelty.

Corticotropin-releasing factor was administered into the lateral cerebral ventricles of rats. Sixty minutes later, animals were tested in an open field conflict test or in their home cages for a variety of behaviors which have been shown to be related to the degree of responsiveness to novelty. CRF, in a dose related fashion, altered the frequency of those behaviors which are normally expressed in response to the novel environment. Specifically, CRF caused an increase in grooming and decreases in the amount of rearing, the number of approaches to a food pellet placed in the center of the open field, the amount of food eaten in both the open field and the home cage and a decrease in the mean amount of food eaten per approach to the food pedestal.

Animals↗
PubMed1982

Calcitonin COOH-terminal cleavage peptide as a model for identification of novel neuropeptides predicted by recombinant DNA analysis.

A strategy is presented for identification of putative neurohormones that were predicted by sequence analysis of recombinant cDNa molecules. The nucleotide sequence of a cloned calcitonin cDNA insert predicts that the proteolytic excision of calcitonin from a 136-amino acid precursor should generate two additional peptides derived from regions flanking the calcitonin sequence on the NH2 and carboxyl termini. The predicted 16-amino acid COOH-terminal cleavage peptide (NH2-Asp-Met-Ala-Lys-Asp-Leu-Glu-Thr-Asn-His-His-Pro-Thr-Phe-Gly-Asn-COOH) was chemically synthesized using solid phase procedures. Antibodies against this synthetic hexadecapeptide detect immunologically cross-reactive material in tissue extracts from normal thyroid glands and calcitonin-producing medullary thyroid carcinomas. Each of the four calcitonin mRNA-directed cell-free translation products contain the immunological determinants for both calcitonin and the COOH-terminal cleavage peptide.

Amino Acid Sequence↗
PubMed1982

Corticotropin-releasing factor: effects on the sympathetic nervous system and oxygen consumption.

Corticotropin-releasing factor administered intracerebroventricularly produces prolonged elevation of plasma concentration of epinephrine, norepinephrine and glucose. These hormonal changes are associated with an increase in motor activity and oxygen consumption. No change in body temperature is observed. CRF produces changes in animal physiology that are similar to those observed in response to stress.

Animals↗
PubMed1982

Pituitary somatostatin receptors: dissociation at the pituitary level of receptor affinity and biological activity for selective somatostatin analogs.

High affinity and saturable binding of [125I-Tyr11]somatostatin (SS) is described in membrane homogenates from a pituitary transplantable tumor (GH4C1) rich in somatotrophs (KD for SS = 0.67 nM; Bmax = 30 fmol/mg protein). Binding characteristics and pharmacology are similar to those measured on normal pituitary membranes. The potency of various SS analogs highly correlates with that measured in in vitro bioassay for growth hormone. This suggests that those GH4C1 membranes are a good model for SS receptors on somatotrophs. Interestingly however, analogs in which the Asn5 is deleted (Des-Asn5) or D-Ser replaces Ser13 show dissociated potencies between the various assays: [D-Ser13] analogs are more potent in pituitary than in GH4C1 membranes binding assay. Des-Asn5-modified analogs are much more potent in both pituitary binding assays than in the bioassay. This could reflect a multiplicity of SS receptor subtypes in pituitary.

Animals↗
PubMed1982

Comparison of the biologic actions of corticotropin-releasing factor and sauvagine.

Corticotropin-releasing factor (CRF), a peptide isolated from ovine hypothalamus, and sauvagine, a peptide isolated from frog skin, share significant structural homology and elicit a number of similar biological responses. CRF is more potent than sauvagine in stimulating pituitary ACTH secretion. Sauvagine, however, is 5-10 times more potent than CRF to act within the brain to increase plasma levels of catecholamines and glucose and to elevate mean arterial pressure. Sauvagine is likewise more potent than CRF to act outside the brain to increase superior mesenteric artery flow and plasma glucose concentrations and to decrease mean arterial pressure. CRF and sauvagine produce important effects representative of biologically active peptides.

Adrenocorticotropic Hormone↗
PubMed1982

Direct inhibition of testicular steroidogenesis and gonadotrophin receptor levels by [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH, potent agonists of GnRH.

The effects of [(imBzl)-D-His6, Pro9-NEt]GnRH and [D-Trp6, Pro9-NEt]GnRH on testicular function in rats was evaluated. In adult rats the administration of 0.01, 0.1 or 10 micrograms of either agonist induced rapid increases in serum LH, FSH and testosterone (T) levels which started to decline within several hours. Both agonists caused a decrease in testicular LH and FSH receptor concentrations. The testicular FSH receptor concentration started to decline earlier than the LH receptor concentration but, both reached their lowest levels by day 2 after the administration of the agonists. The recovery of FSH receptor content was slower than that of LH. The extrapituitary effects of the 2 agonists were investigated in immature hypophysectomized animals. Administration of hCG (5 IU daily) to hypophysectomized rats for 5 days caused an increase in serum T levels. Concomitant administration of either of the agonists (10 micrograms) inhibited the steroidogenic action of hCG. Administration of the agonists alone caused a reduction in testicular LH receptor concentration in hypophysectomized rats. Treatment of the hypophysectomized rats for 0-4 days suggested that the direct antitesticular action of the agonists requires 1-2 days to become evident.

Animals↗
PubMed1982

Amunine (ovine CRF), urotensin I and sauvagine, three structurally-related peptides, produce selective dilation of the mesenteric circulation.

Three synthetic peptides, urotensin I, sauvagine and ovine CRF, have less than 50% sequence homology. In the dog, all three produce selective mesenteric dilation, which appears to be solely responsible for a decrease in peripheral resistance and systemic arterial blood pressure. Urotensin I and sauvagine were found to be 5-10 times more potent than CRF.

Amphibian Proteins↗