Psychiatry related information on TRH

• Locomotor activity in Xenopus males was increased significantly after 15 min following TRH injection (150 micrograms); this effect persisted for at least 1 hr [1].

High impact information on TRH

• Skin of Xenopus laevis contains relatively large quantities of thyrotropin releasing hormone (TRH) [2].
• It is concluded that the cloned part of the mRNA codes for prepro-TRH and that the TRH precursor from skin of X. laevis is a polyprotein containing at least four copies of the end product in its amino acid sequence [2].
• The responsiveness on the two hemispheres to TRH and AcCho in mRNA-injected oocytes is opposite to that for the common intrinsic AcCho response in that there is a much greater response when agonist is applied at the animal rather than the vegetal hemisphere [3].
• By contrast, the acquired responses to TRH and AcCho are characterized by much longer latencies, 9.3 +/- 1.0 and 5.5 +/- 0.8 sec, respectively, and large rapid depolarizations followed by less distinct prolonged depolarizations [3].
• We studied depolarizing chloride currents evoked by acetylcholine (AcCho) in native oocytes ("intrinsic AcCho response"), by thyrotropin-releasing hormone (TRH) in oocytes injected with pituitary (GH3) cell RNA ("acquired TRH response"), and by AcCho in oocytes injected with rat brain RNA ("acquired AcCho response") [3].

Biological context of TRH

• The ability of AII and TRH to act by way of newly synthesized receptors from mammalian endocrine tissues to stimulate phosphatidylinositol polyphosphate hydrolysis in Xenopus oocytes suggests a generalized and conserved mechanism of receptor coupling to the transduction mechanism responsible for activation of phospholipase C in the plasma membrane [4].
• A mutant Galpha16 with four consensus PKC phosphorylation sites removed is not phosphorylated in vivo, and TRH responses mediated through the mutant are not regulated by PKC [5].
• Whereas wild-type G(o)alpha increased TRH-promoted chloride currents, S47C significantly decreased the hormone-induced Cl- response, suggesting that this mutation resulted in a dominant negative phenotype [6].
• We suggest that oocytes injected with GH3 cell RNA, because of their large size and easy access to their intracellular milieu, will be a useful intact cell model in which to define the molecular details of signal transduction by TRH [7].
• Acetylcholine (ACh) and thyrotropin-releasing hormone (TRH) utilize inositol 1,4,5-trisphosphate (IP3) as a second messenger and evoke independent depolarizing membrane electrical responses accompanied by characteristic 45Ca efflux profiles in Xenopus laevis oocytes injected with GH3 pituitary cell mRNA [8].

Anatomical context of TRH

• It is concluded that GnRH (and TRH) receptors, expressed in Xenopus oocytes by injecting exogenous mRNA from rat anterior pituitary glands, operate via activation of Ca2+-dependent Cl- channels [9].
• The TRH neuronal phenotype forms embryonic cell clusters that go on to establish a regionalized cell fate in forebrain [10].
• Localization studies combining in situ hybridization and immunocytochemistry showed that, at least in optic tectum and brainstem, PC2 mRNA and pro-TRH peptide coexist [11].
• Thereafter, the TRH cell clusters in diencephalon, but not hindbrain, expanded to form rows, extending anteriorly into telencephalon and bifurcating posteriorly around the infundibulum [10].
• Using similar procedures it was demonstrated that TRH extended peptides were present in bovine hypothalamus [12].

Associations of TRH with chemical compounds

• It is concluded that Gs, but not Go, Gq, Gi, or Gz, couples TRH receptors expressed in oocytes to activation of phospholipase C and subsequent inositol 1,4,5-trisphosphate-dependent stimulation of Ca(2+)-dependent Cl- currents [13].
• The response to TRH was dose dependent and was inhibited by the TRH antagonist, chlordiazepoxide [7].
• The depolarizing response to TRH was not diminished in oocytes incubated in a Ca2(+)-free medium, but was inhibited by microinjection of EGTA [7].
• TRH caused rapid hydrolysis of labeled phosphatidylinositol 4,5-bisphosphate and a marked, prolonged increase in 45Ca2+ efflux from injected oocytes [7].
• Cells not pulsing spontaneously were responsive to dopamine, GABA, and NPY and pulsed in response to the secretagogues CRF and TRH [14].

Co-localisations of TRH

• Frog prohormone convertase PC2 mRNA has a mammalian-like expression pattern in the central nervous system and is colocalized with a subset of thyrotropin-releasing hormone-expressing neurons [11].

Regulatory relationships of TRH

• We recently discovered that melanotrophs of Xenopus laevis exhibit spontaneous pulse-like rises in cytosolic free calcium ([Ca2+]i) and that this cytosolic Ca pulsing is inhibited by the secreto-inhibitory transmitters dopamine, gamma-aminobutyric acid, and neuropeptide-Y and stimulated by the secretagogues CRF and TRH [15].

Other interactions of TRH

• High performance liquid chromatography (HPLC) of crude and Sephadex G-10 chromatographed secretions showed that many more peptides were present in these secretions than those previously identified, i.e., xenopsin, caerulein, TRH and PGLa [16].
• Dopamine had little effect alone, but inhibited HE- and TRH-stimulated release of prolactin, but not GH, in both amphibia and reptiles [17].
• Thyrotropin-releasing hormone receptor (TRHR) has already been cloned in mammals wherethyrotropin-releasing hormone (TRH) is known to act as a powerful stimulator of thyroid-stimulating hormone (TSH) secretion [18].

Analytical, diagnostic and therapeutic context of TRH

• However, Northern blot analysis of TRH precursor mRNAs in the brain of X. laevis revealed the existence of a new mRNA of about 1200 nucleotides which was present along with the larger TRH precursor mRNA identified in the skin [19].
• Plasma levels of TRH, determined with a specific radioimmunoassay, proved to be extremely high and no significant difference in this level could be found between white- and black-adapted animals [20].
• To study the role of sauvagine, cAMP, TRH and phorbol 12-myristate 13-acetate (PMA) in the regulation of POMC biosynthesis, the degree of incorporation of radioactive amino acids into the POMC protein was determined after treatment of the neurointermediate lobes with these secretagogues [21].
• Calcium waves and dynamics visualized by confocal microscopy in Xenopus oocytes expressing cloned TRH receptors [22].
• Localisation by immunofluorescence of thyrotropin-releasing hormone in the cutaneous glands of the frog, Rana ridibunda [23].

References