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Query: HUMANGGP:012528 (thyrotropin-releasing hormone)
 3,440 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of liquid protein diet (LPD), known to be poor in protein quality, on brain thyrotropin-releasing hormone (TRH) and histidylproline diketopiperazine (cyclo(His-Pro] were examined in young male rats. At day 23 of weaning, the animals were fed either a 20% casein diet ad libitum or a 20% LPD, or were pair-fed with a 20% casein diet. They were decapitated at day 48. The body weight of those in the LPD and pair-fed groups decreased significantly, and the loss was sustained in comparison with that in the ad libitum group. Cyclo(His-Pro) concentrations in the whole brain were significantly greater in the LPD group than in the pair-fed and ad libitum groups, whereas its concentrations were similar in the pair-fed and ad libitum groups. No significant differences were observed in concentrations of brain TRH in the three groups. These findings indicate that quality of the protein component in the diet contributes to alterations in the neuropeptide, cyclo(His-Pro), in the young rat brain.
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PMID:Alteration by liquid protein diet of TRH and cyclo(His-Pro) in the young rat brain. 392 Jul 37

An abiotic system is described which chemically catalyzes the formation of less than Glu-His-Pro-NH2 (thyrotropin-releasing hormone) from less than Glu-His-Pro-amino acid in the presence of copper, ascorbate, and molecular oxygen. Evidence is presented to support the participation of hydroxyl and carbon radicals as reaction intermediates in the production of a peptide amide and an aldehyde or ketone. The characteristics of this model system closely mimic the characteristics of enzymatic peptide amidation, and an oxidative, free-radical mechanism for enzymatic peptide amidation is proposed as an alternative to the mechanism for enzymatic amidation offered by Bradbury et al. (Bradbury, A. F., Finnie, M. D. A., and Smyth, D. G. (1982) Nature 298, 686-688).
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PMID:Nonenzymatic peptide alpha-amidation. Implications for a novel enzyme mechanism. 392 62

A rabbit antiserum to a peptide sequence present in the precursor for thyrotropin-releasing hormone (proTRH), deduced from cloned amphibian-skin complementary DNA, was raised by immunization with the synthetic decapeptide Cys-Lys-Arg-Gln-His-Pro-Gly-Lys-Arg-Cys (proTRH-SH). Immunohistochemical studies on rat brain tissue showed staining of neuronal perikarya in the parvicellular division of the paraventricular nucleus of the hypothalamus and the raphe complex of the medulla, identical to that already described for thyrotropin-releasing hormone (TRH). Immunostaining was abolished by preincubation with proTRH-SH (10(-6)M) but not TRH (10(-5)M). Both TRH precursor and TRH were located in neurons of the paraventricular nucleus. However, in contrast to the findings for TRH, no staining was observed in axon terminals of the median eminence. These results suggest that a TRH precursor analogous to that reported in frog skin is present in the rat brain and that TRH in the mammalian central nervous system is a product of ribosomal biosynthesis.
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PMID:Immunohistochemical localization in the rat brain of the precursor for thyrotropin-releasing hormone. 392 78

Pancreatic islets contain large-quantities of thyrotropin-releasing hormone (TRH) and of its metabolite Histidyl-Proline diketopiperazine (Cyclo His-Pro). The effects of these two putative neurotransmitters on the pancreatic B-cell function have been evaluated in vitro, with islets of normal or dysthyroid mice. TRH and Cyclo His-Pro (10(-11)-10(-6) M) were without effect on insulin release induced by 10-20 mM glucose in islets of normal mice. They transiently accelerated the slow waves of membrane potential triggered in B cells by 10 mM glucose, but did not cause any sustained change in overall electrical activity, and did not affect the rate of 86Rb+ efflux from islet cells. They were also ineffective when insulin release was stimulated by leucine or arginine, or was potentiated by forskolin, an activator of the adenylate cyclase. Hyperthyroidism (induced by injections of thyroxine) caused a fall in islet insulin content, but augmented the 2 phases of glucose-induced release. On the other hand, hypothyroidism (induced by a low iodine diet and propylthiouracil) caused an increase in islet insulin content, but depressed the second phase of release. TRH did not affect either phase of insulin release by islets of hyperthyroid or hypothyroid mice. These results show that pancreatic B cells are not a target for TRH and Cyclo His-Pro.
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PMID:Thyrotropin-releasing hormone and insulin release: in vitro studies with islets of normal and dysthyroid mice. 393 Jan 25

Fresh human semen, diluted 1:1 v/v with 0.15 M NaCl- 0.05 M phosphate, pH 7.5, undergoes a 3-fold increase in total thyrotropin-releasing hormone (TRH) immunoreactivity on incubation at 4 C for 8 to 16 hours. To identify the mechanism for this increase, pooled human semen was incubated at 4, 37, and 60 C, and the change in composition of the immunoreactive TRH peptides was quantitated by high pressure liquid chromatography and radioimmunoassay of TRH. His-Pro diketopiperazine, a biologically active metabolite of TRH consisting of a cyclic dipeptide of histidine and proline, also was measured by specific RIA. The concentration of TRH (pGlu-His-Pro-NH2) dropped precipitously within the first hour after dilution and incubation at all temperatures studied. A hydrophobic TRH-homologous peptide with the amino acid composition (Glu,X,Y,Pro), where X and Y are neutral, nonaromatic amino acids, increased 8-fold during 16 hours of incubation at 4 C. This TRH-homologous peptide is not derived from TRH because it lacks the histidine is not derived from TRH because it lacks the histidine residue. A 3- to 23-fold increase in His-Pro diketopiperazine levels occurred after 4 hours at 37 C. This was not due primarily to enzymatic removal of the pyroglutamyl residue from TRH by pyroglutamate aminopeptidase, since about 1 hour after ejaculation the initial His-Pro diketopiperazine levels were 9.7 +/- 5.1 micrograms/ml, or approximately 1000-fold greater than the corresponding levels of seminal TRH. Because cycloheximide, which blocks ribosomal protein biosynthesis, did not inhibit in vitro production of the TRH-homologous peptide and the His-Pro cyclic dipeptide, these peptides, like TRH, most likely arise from post-translational cleavage and processing from pre-existing macromolecular precursor proteins.
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PMID:In vitro production of a TRH-homologous peptide and His-Pro diketopiperazine by human semen. 393 36

Biosynthesis of thyrotropin-releasing hormone (L-pyroglutamyl-L-histidyl-L-proline amide) in vitro was studied. Rat hypothalamic fragments were incubated in Krebs-Ringer bicarbonate buffer that contained either (14)C-labeled proline, histidine, or glutamic acid (the three probable precursor amino acids,) and for control purposes each of 16 other naturally occurring amino acids. A number of labeled peptides were synthesized. With the use of synthetic thyrotropin-releasing hormone, detected by the Pauly reagent or with (125)1-labeled thyrotropin-releasing hormone as a marker, thin-layer chromatograms, paper electrophoresis, and carboxymethyl cellulose ion exchange chromatography revealed that only proline, histidine, and glutamic acid were consistently incorporated into peptides associated with the thyrotropin-releasing hormone region. This synthesizing activity was found in stalk median eminence, ventral hypothalamus. and dorsal hypothalamus but not in neural lobe or cerebral cortex. Because the biosynthetic peptide has identical properties with L-pyroglutamyl-L-histidyl-L-proline amide, it is probable that rat thyrotropin-releasing hormone is similar or identical to both bovine and porcine thyrotropin-releasing hormone and that the native material is present in the pyroglutamyl form in tissues.
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PMID:Thyrotropin-releasing hormone: biosynthesis by rat hypothalamic fragments in vitro. 499 24

We studied whether protein-energy malnutrition changed brain susceptibility to a small dose of caffeine in newborn rats. Since we had demonstrated previously that caffeine intake during lactation increased the brain neuropeptide on newborns, we investigated further the effects of the prenatal administration of caffeine on TRH and cyclo (His-Pro). From day 13 of gestation to delivery day, pregnant rats in one group were fed either a 20% or a 6% protein diet ad libitum, and those in the other group were pair-fed with each protein diet supplemented with caffeine at an effective dose of 2 mg/100 g body weight. Upon delivery, brain weight, brain protein, RNA, DNA and the neuropeptides thyrotropin-releasing hormone (TRH) and cyclo (His-Pro) were measured in the newborn rats. A 6% protein without caffeine diet caused reductions in brain weights and brain protein, RNA and DNA contents, but did not alter brain TRH and cyclo (His-Pro) concentrations in the newborn animals. In the offspring from dams fed a 6% protein diet, caffeine administration significantly elevated brain weights and brain contents of protein, RNA and DNA. In contrast, these values were similar between noncaffeine and caffeine-supplemented animals in a 20% protein diet group. Brain TRH and cyclo (His-Pro) concentrations were not changed by caffeine administration. These data suggest that caffeine augments protein synthesis in the newborn rat brain when malnourished, but that the same dose of caffeine did not affect protein synthesis in brains of newborn rats from normally nourished dams. Therefore, the present findings indicate that the nutritional status of mothers during pregnancy has important implication in the impact of caffeine on their offspring's brains.
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PMID:Protein-energy malnutrition during pregnancy alters caffeine's effect on brain tissue of neonate rats. 608 28

In the present study, we describe the biochemical characteristics and the autoradiographic distribution of thyrotropin-releasing hormone (TRH) receptors in the rat central nervous system (CNS) after in vitro incubation of brain slices with 3H-TRH. Scatchard analysis showed that, in the range of concentrations tested (0.7-35 nM), 3H-TRH bound to a single-class of receptors with a dissociation constant of 6 nM and a number of binding sites of 20 fmol/mg protein. Increasing concentrations of unlabeled TRH produced a dose-dependent inhibition of 3H-TRH binding. The only analogue as potent as TRH to displace 3H-TRH binding was 3-Me-TRH, whereas 1-Me-TRH or TRH-free acid as well as pGlu-His, pGlu-Pro-NH2 or His-Pro-diketopiperazine were ineffective. Neither Luteinizing hormone-releasing hormone (LHRH), neurotensin, somatostatin, D-Ala-Met-enkephalin nor VIP showed any significant affinity for TRH binding sites. Autoradiograms obtained by apposition of LKB 3H-Ultrofilm showed that the highest concentrations of 3H-TRH binding sites were found in the ventral dentate gyrus of the hippocampal formation, the lateral amygdaloid nucleus, the nucleus accumbens, and the thalamic paraventricular nucleus. The biochemical characterization of 3H-TRH binding in brain sections is in good agreement with previous reports on membrane preparations and the autoradiographic localization of the binding sites provides anatomical support for the effects of TRH in the CNS.
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PMID:In vitro biochemical characterization and autoradiographic distribution of 3H-thyrotropin-releasing hormone binding sites in rat brain sections. 608 85

Cyclo(Histidyl-Proline) is a metabolite of thyrotropin-releasing hormone. It has been suggested that this peptide plays a role in regulating prolactin secretion in GH cells. An investigation of the effect of cyclo(His-Pro) on GH cells indicated that it does not affect basal prolactin release or accumulation or the levels stimulated by TRH. cAMP levels in GH cells are elevated by TRH or VIP, but not influenced by cyclo(His-Pro). cGMP levels in GH cells are not affected by either TRH or cyclo(His-Pro). While there is specific binding of TRH to receptors in GH cells, no such receptors for cyclo(His-Pro) are detectable. It is suggested that GH cells are unresponsive to cyclo(His-Pro).
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PMID:Unresponsiveness of GH cells to cyclo(histidyl-proline), a metabolite of thyrotropin releasing hormone. 609 58

The distribution of cyclo(His-Pro), thyrotropin-releasing hormone (TRH) and Pyroglutamate aminopeptidase activity in adult and developing rat brains were studied. A comparison of the subcellular distribution of Pyroglutamate aminopeptidase activity in hypothalamic and cerebral cortical extracts from adult rats exhibited remarkable differences. In hypothalamus, the enzyme activity was mainly associated with the soluble fraction whereas in cortex it was predominantly associated with the particulate fractions. During postnatal development, the brain concentrations of cyclo(His-Pro) and Pyroglutamate aminopeptidase activities declined with age. These data suggest that Pyroglutamate aminopeptidase activity, but not TRH, plays an active role in determining the levels of endogenous cyclo(His-Pro) concentrations in brain.
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PMID:Developmental changes in the distribution of rat brain pyroglutamate aminopeptidase, a possible determinant of endogenous cyclo(His-Pro) concentrations. 613 45


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