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Biomedical subjects

T W Redding

Publications and source records attributed to T W Redding.

At least 73 records · Page 4Linked to original sources
PubMed1980

Isolation and structure of pro-somatostatin: a putative somatostatin precursor from pig hypothalamus.

An octacosapeptide that we named pro-somatostatin has been isolated from acid extracts of porcine hypothalami and found to have the amino acid sequence Ser-Ala-Asn-Ser-Asn-Pro-Ala-Met-Ala-Pro-Arg-Glu-Arg-Lys-Ala-Gly-Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys. This octacosapeptide possesses high somatotropin (growth hormone) and prolactin release-inhibiting activity in vitro. It also crossreacts strongly with antisera generated against the somatostatin tetradecapeptide. This octacosapeptide is most likely a precursor (pro-hormone) of somatostatin in the hypothalamus. The existence of still larger molecular size precursors of somatostatin was also observed.

Amino Acid Sequence↗
PubMed1978

Highly active position eight analogues of somatostatin and separation of peptide diastereomers by partition chromatography.

Six stereochemically pure analogues of somatostatin (SS), D- and L-5F-Trp8-SS, D- and L -6F-Trp8-SS, and D- and L-5Br-Trp8-SS, were synthesized and found to be more potent than somatostatin in suppressing the release of growth hormone from cultured rat pituitary cells. Two of the analogues, D-5F-Trp8- and D-5Br-Trp8-SS, were respectively 25 and 30 times more active than somatostatin in that assay. The analogues were prepared by solid phase synthesis of their corresponding diastereomeric mixtures, followed by their complete resolution by preparative partition chromatography. Reversed phase high pressure liquid chromatography (HPLC) was used to monitor the resolution and also to check the final purity of each peptide. Positive identification of each diastereoisomer was determined by amino acid analyses of their enzymatic digests, direct comparison with a known all-L standard in the case of the 5F-Trp8 analogues, and chromatographic separation of dansylated amino acids following enzymatic digestion of D- and L-5Br-Trp8-SS. The role of tryptophan in somatostatin is discussed and it is suggested that maintenance of physiological activity in somatostatin peptides, at least on the pituitary, is partially dependent upon the degree of resonance in the indole nucleus in position 8.

Cells, Cultured↗
PubMed1978

Disapearance and excretion of labeled alpha-MSH in man.

Despite the considerable evidence for the CNS actions of alpha-melanocyte-stimulating hormone (alpha-MSH) in man, little attention has been given to its half-time disappearance from plasma and urinary excretion in normal individuals. In the first experiment, a healthy man was given 15 muCi of tritiated (3H)-alpha-MSH as a rapid IV injection. A plot of the disappearance time in plasma was characteristic of a multiexponential curve, the linear components of which were resolved by the subtraction method and half-time disappearance calculated directly from the slope of the regression line. The half-time disappearance was 1 min for the first component and 25 min for the second component. After the IV adminisration of 50 muCi of 125I-alpha-MSH in the second experiment, the two components showed halftime disappearances of 1 min and 4.8 min respectively. These times were not changed by precipitation of the plasma with 10% trichloroacetic acid. Thirty-eight percent and 42% of the label appeared in the urine 4 hr after the injection of either 3H-alpha-MSH or 125I-alpha-MSH. The results suggest that the persistence of high levels of alpha-MSH in the blood after injection in man may be too short to fully explain the CNS effects of alpha-MSH.

Humans↗
PubMed1977

Isolation of gamma-amino butyric acid from pig hypothalami and demonstration of its prolactin release-inhibiting (PIF) activity in vivo and in vitro.

A non-retarded fraction with prolactin-release inhibiting factor (PIF) activity obtained by chromatography of a concentrate of porcine hypothalami on carboxymethyl-cellulose was chromatographically distinct from catecholamines. This fraction was purified further by six steps involving chromatography on Sephadex G-25, countercurrent distribution, free-flow electrophoresis, and chromatography on triethylaminoethyl cellulose. The PIF-active substance was isolated and identified as gamma-amino-butyric acid (GABA) by: 1) amino acid analyses using sodium as well as lithium-based buffers for resolution of biological fluids, 2) thin-layer chromatography of underivatized material as well as phenylthiocarbamyl derivatives, and 3) mass spectroscopy. Natural and synthetic GABA inhibited prolactin, but not LH release in vitro from isolated rat pituitary halves at doses as low as 0.1 microgram/ml. The inhibition was proportional to the dose; natural and synthetic GABA possessed identical PIF activity. Synthetic GABA also decreased prolactin release in monolayer cultures of rat pituitary cells and inhibited TRH-stimulated prolactin release. The inhibition of prolactin release in vitro by GABA could not be blocked by perphenazine, which inhibits PIF activity of catecholamines. GABA also suppressed prolactin release in vivo, although large doses were needed. Either rapid iv injection or infusion of GABA in doses of 1 to 100 mg in rats significantly decreased serum prolactin levels, which were previously elevated by pretreatment with monoiodotyrosine perphenazine, chlorpromazine, haloperidol, or sulpiride. beta-hydroxy GABA significantly depressed prolactin release, but beta-(p-chlorophenyl)-GABA (Lioresal, CIBA) and 4 other analogs of GABA were not effective in vivo and/or in vitro. The results indicate that GABA can inhibit prolactin release by a direct action on the pituitary gland, but whether this effect is physiologically meaningful still remains to be determined.

Animals↗
PubMed1976

Isolation and structure of somatostatin from porcine hypothalami.

The isolation and structure of somatostatin (GH-RIH) from pig hypothalami are described. This hormone was purified by preparative gel filtration, solvent extraction, countercurrent distribution in two solvent systems, ion-exchange and partition chromatography, and analytical gel filtration. The somatostatin activity was followed by in vitro bioassays and a radioimmunoassay. The isolated product was homogeneous chromatographically and had biological and immunological properties similar to synthetic somatostatin corresponding to the ovine hormone. The primary structure of porcine somatostatin was shown to be H-Ala-Gly-cyclo-(Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys)-OH. Other immunologically and biologically active form(s) of somatostatin were also detected.

Amino Acid Sequence↗
PubMed1976

Re-examination of porcine and bovine hypothalamic fractions for additional luteinizing hormone and follicle stimulating hormone-releasing activities.

More than 150 hypothalamic fractions were reassayed for luteinizing hormone-releasing hormone (LHRH) and follicle stimulating hormone-releasing hormone (FSHRH) activities in search for LHRH and FSHRH which differ from the decapeptide (pyro)Glu-His-Trp-Ser-Try-Gly-Leu-Arg-Pro-Gly-NH2 (I). Among the porcine fractions tested were those obtained: 1) from the isolation of thyrotropin-releasing hormone; 2) from two isolation procedures for LHRH; and 3) from methanolic and aqueous 2N acetic acid extracts which were subjected to Biogel P-2 filtration and partition chromatography. Some bovine hypothalamic fractions were also tested. Both in vivo and in vitro assays were used for measuring LHRH and FSHRH activities. The values obtained were in each case compared with those resulting from the administration of pure natural or synthetic LHRH decapeptide I. A radioimmunoassay for LHRH (I) was also utilized for some fractions. In all the purification steps the location of LHRH and FSHRH activity, as determined by in vivo assays, corresponded to that of the decapeptide I. Purification of hypothalamic extracts on Biogel P-2 and by partition chromatography separated a fraction from the decapeptide I, which released more FSH than LH in vitro from the pituitaries of immature female rats. However, this material was inactive in vivo and in other in vitro systems, so that its significance is obscure. The results suggest that if material with LHRH and FSHRH activity other than the decapeptide I is present in acid extracts of porcine hypothalami, then its FSHRH and LHRH activity would be a minor part of the total LHRH/FSHRH activity in the extracts. (Pyro)-Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 appears to account for most of all of the LHRH and FSHRH activity found.

Animals↗
PubMed1975

Synthesis and biological properties of the 2-L-beta-(pyrazolyl-1)alanine analogs of luteinizing hormone-releasing hormone and thyrotropin-releasing hormone.

The luteinizing hormone-releasing hormone (LH-RH) analog, less thanGlu-Pyr(1)Ala-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, and the thyrotropin-releasing hormone (TRH) analog, less thanGlu-Pyr(1)Ala-Pro-NH2, were synthesized by azide couplings of the dipeptide hydrazide, less thanGlu-Pyr(1)Ala-NHNH2, to the C-terminal octapeptide of LH-RH and to proline amide, respectively. In an ovariectomized, steroid-blocked rat assay, the LH-RH analog was found to have only 1% of the LH-releasing activity of the natural hormone. The TRH analog was 1.5 times more effective than TRH itself in releasing TSH in vivo from the anterior pituitary of mice. This peptide is one of two synthetic peptides so far discovered which are more potent than TRH.

Alanine↗
PubMed1975

Purification and characterisation of two porcine hypothalamic fractions with LH-releasing activity: evidence for a single LH and FSH-releasing hormone.

Two fractions with LH releasing activity were obtained from porcine hypothalami by Enzmann et al. (1972). These fractions were designated E 57 and E 203. By comparison with pure natural LH-RH and synthetic LH-RH, E 203 was identified as purified natural LH-RH. E 57, which has only 25% of the activity of E 203, was further evaluated for its biological and immunological activity. E 57 has the same ratio of LH/FSH-releasing activity as natural LH-RH. The binding to a specific LH-RH antiserum is identical with that of natural LH-RH and E 203. It is concluded, that E 57 is an artifact of isolation derived from natural LH-RH. These findings can be considered as additional evidence for the identity of the hypothalamic LH and FSH releasing hormone, since both gonadotrophins are stimulated by the two hypothalamic fractions.

Animals↗
PubMed1975

Lipid mobilizing hormones of the hypothalamus and pituitary.

Lipid mobilizing substances (LMS) are present in the hypothalamus and pituitary of mammals and probably are involved in the central neural control of obesity. Most of these have direct lipolytic effects, like lipid mobilizing factor (LMF) and LH-RH from the hypothalamus as well as lipotropin (LPH), melanocyte-stimulating hormone (MSH), corticotropin (ACTH), and growth hormone (GH) from the pituitary gland. Some of the substances, like GH-release inhibiting hormone (GH-RIH), affect lipolysis by secondary actions on pancreatic hormones such as insulin and glucagon. Other hypothalamic hormones, like GH-releasing hormone (GH-RH) may influence lipolysis secondarily through the pituitary hormones (e.g. GH) whose release they control. Regardless of how lipid mobilization is affected, investigations into the problem of obesity should take these LMS into consideration.

Adipose Tissue↗