This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nillni, E. A. Articles by Sevarino, K. A. Search for Related Content PubMed PubMed Citation Articles by Nillni, E. A. Articles by Sevarino, K. A.

The Biology of pro-Thyrotropin-Releasing Hormone-Derived Peptides¹

Division of Endocrinology (E.A.N.), Department of Medicine, Brown University School of Medicine, Rhode Island Hospital, Providence, Rhode Island 02903; and Yale University School of Medicine and Connecticut Veterans Affairs Healthcare System (K.A.S.), Department of Psychiatry, Research 151, West Haven, Connecticut 06516

I. Introduction

II. Biosynthesis of TRH and Other pro-TRH-Derived Peptides

A. Biosynthesis and processing of pro-TRH

B. Intracellular sites of pro-TRH processing

C. Tissue-specific processing of pro-TRH

D. The role of PCs and CPs

E. Neuropeptide and catecholamine regulation of Pro-TRH biosynthesis and processing

F. Glucocorticoids modulate the biosynthesis and processing of pro-TRH

G. Leptin regulates pro-TRH biosynthesis

III. Function of TRH

A. The HPT axis

B. Extrahypophysiotropic TRH

IV. Function of non-TRH pro-TRH-Derived Peptides

A. prepro-TRH_160–169 (pST₁₀)

B. prepro-TRH_178–199 (pFE₂₂)

C. prepro-TRH_178–185 and prepro-TRH_186–199 (pFQ₇ and pSE₁₄)

D. prepro-TRH_53–74 (pFT₂₂)

E. prepro-TRH_83–106 (pEH₂₄) and prepro-TRH_208–255

F. TRH-Gly

V. Non-TRH pro-TRH-Derived Peptides Outside of the CNS

VI. TRH and Other pro-TRH-Derived Peptide Receptors

A. The TRH receptor

B. The prepro-TRH_160–169 (pST₁₀) receptor

VII. TRH Degradation

VIII. Concluding Remarks

This article has been cited by other articles:

				M. Perello, R. Stuart, and E. A. Nillni Prothyrotropin-releasing Hormone Targets Its Processing Products to Different Vesicles of the Secretory Pathway J. Biol. Chem., July 18, 2008; 283(29): 19936 - 19947. [Abstract] [Full Text] [PDF]

				H. Zeng, B. A. Schimpf, A. D. Rohde, M. N. Pavlova, A. Gragerov, and J. E. Bergmann Thyrotropin-Releasing Hormone Receptor 1-Deficient Mice Display Increased Depression and Anxiety-Like Behavior Mol. Endocrinol., November 1, 2007; 21(11): 2795 - 2804. [Abstract] [Full Text] [PDF]

				M. Perello, R. C. Stuart, C. A. Vaslet, and E. A. Nillni Cold Exposure Increases the Biosynthesis and Proteolytic Processing of Prothyrotropin-Releasing Hormone in the Hypothalamic Paraventricular Nucleus via {beta}-Adrenoreceptors Endocrinology, October 1, 2007; 148(10): 4952 - 4964. [Abstract] [Full Text] [PDF]

				E. A. Nillni Regulation of Prohormone Convertases in Hypothalamic Neurons: Implications for ProThyrotropin-Releasing Hormone and Proopiomelanocortin Endocrinology, September 1, 2007; 148(9): 4191 - 4200. [Abstract] [Full Text] [PDF]

				M. Perello, R. C. Stuart, and E. A. Nillni Differential effects of fasting and leptin on proopiomelanocortin peptides in the arcuate nucleus and in the nucleus of the solitary tract Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1348 - E1357. [Abstract] [Full Text] [PDF]

				V. P. Espinosa, M. Ferrini, X. Shen, K. Lutfy, E. A. Nillni, and T. C. Friedman Cellular colocalization and coregulation between hypothalamic pro-TRH and prohormone convertases in hypothyroidism Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E175 - E186. [Abstract] [Full Text] [PDF]

				P.-Y. Deng, J. E. Porter, H.-S. Shin, and S. Lei Thyrotropin-releasing hormone increases GABA release in rat hippocampus J. Physiol., December 1, 2006; 577(2): 497 - 511. [Abstract] [Full Text] [PDF]

				K. Matlhagela and M. Taub Regulation of the Na-K-ATPase beta1-subunit promoter by multiple prostaglandin-responsive elements Am J Physiol Renal Physiol, September 1, 2006; 291(3): F635 - F646. [Abstract] [Full Text] [PDF]

				L. Chavez-Gutierrez, E. Matta-Camacho, J. Osuna, E. Horjales, P. Joseph-Bravo, B. Maigret, and J.-L. Charli Homology Modeling and Site-directed Mutagenesis of Pyroglutamyl Peptidase II: INSIGHTS INTO OMEGA-VERSUS AMINOPEPTIDASE SPECIFICITY IN THE M1 FAMILY J. Biol. Chem., July 7, 2006; 281(27): 18581 - 18590. [Abstract] [Full Text] [PDF]

				M. Perello, R. C. Stuart, and E. A. Nillni The Role of Intracerebroventricular Administration of Leptin in the Stimulation of Prothyrotropin Releasing Hormone Neurons in the Hypothalamic Paraventricular Nucleus Endocrinology, July 1, 2006; 147(7): 3296 - 3306. [Abstract] [Full Text] [PDF]

				M. Perello, T. Friedman, V. Paez-Espinosa, X. Shen, R. C. Stuart, and E. A. Nillni Thyroid Hormones Selectively Regulate the Posttranslational Processing of Prothyrotropin-Releasing Hormone in the Paraventricular Nucleus of the Hypothalamus Endocrinology, June 1, 2006; 147(6): 2705 - 2716. [Abstract] [Full Text] [PDF]

				L. R. Mulcahy, C. A. Vaslet, and E. A. Nillni Prohormone-Convertase 1 Processing Enhances Post-Golgi Sorting of Prothyrotropin-releasing Hormone-derived Peptides J. Biol. Chem., December 2, 2005; 280(48): 39818 - 39826. [Abstract] [Full Text] [PDF]

				R. Guillemin Hypothalamic hormones a.k.a. hypothalamic releasing factors J. Endocrinol., January 1, 2005; 184(1): 11 - 28. [Abstract] [Full Text] [PDF]

				H. Jin, G. Fedorowicz, R. Yang, A. Ogasawara, F. Peale, T. Pham, and N. F. Paoni Thyrotropin-Releasing Hormone Is Induced in the Left Ventricle of Rats With Heart Failure and Can Provide Inotropic Support to the Failing Heart Circulation, May 11, 2004; 109(18): 2240 - 2245. [Abstract] [Full Text] [PDF]

				L. Huo, H. Munzberg, E. A. Nillni, and C. Bjorbaek Role of Signal Transducer and Activator of Transcription 3 in Regulation of Hypothalamic trh Gene Expression by Leptin Endocrinology, May 1, 2004; 145(5): 2516 - 2523. [Abstract] [Full Text] [PDF]

				E. Jing, E. A. Nillni, V. C. Sanchez, R. C. Stuart, and D. J. Good Deletion of the Nhlh2 Transcription Factor Decreases the Levels of the Anorexigenic Peptides {alpha} Melanocyte-Stimulating Hormone and Thyrotropin-Releasing Hormone and Implicates Prohormone Convertases I and II in Obesity Endocrinology, April 1, 2004; 145(4): 1503 - 1513. [Abstract] [Full Text] [PDF]

				X. Lu, I. Bidaud, A. Ladram, and M. C. Gershengorn Pharmacological Studies of Thyrotropin-Releasing Hormone (TRH) Receptors from Xenopus laevis: Is xTRHR3 a TRH Receptor? Endocrinology, May 1, 2003; 144(5): 1842 - 1846. [Abstract] [Full Text] [PDF]

				K. A. Gary, K. A. Sevarino, G. G. Yarbrough, A. J. Prange Jr., and A. Winokur The Thyrotropin-Releasing Hormone (TRH) Hypothesis of Homeostatic Regulation: Implications for TRH-Based Therapeutics J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 410 - 416. [Abstract] [Full Text] [PDF]

				E. A. Nillni, W. Xie, L. Mulcahy, V. C. Sanchez, and W. C. Wetsel Deficiencies in Pro-thyrotropin-releasing Hormone Processing and Abnormalities in Thermoregulation in Cpefat/fatMice J. Biol. Chem., December 6, 2002; 277(50): 48587 - 48595. [Abstract] [Full Text] [PDF]

				C. S. Mantzoros, M. Ozata, A. B. Negrao, M. A. Suchard, M. Ziotopoulou, S. Caglayan, R. M. Elashoff, R. J. Cogswell, P. Negro, V. Liberty, et al. Synchronicity of Frequently Sampled Thyrotropin (TSH) and Leptin Concentrations in Healthy Adults and Leptin-Deficient Subjects: Evidence for Possible Partial TSH Regulation by Leptin in Humans J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3284 - 3291. [Abstract] [Full Text] [PDF]

				E. A. Nillni, F. Aird, N. G. Seidah, R. B. Todd, and J. I. Koenig PreproTRH178-199 and Two Novel Peptides (pFQ7 and pSE14) Derived from Its Processing, Which Are Produced in the Paraventricular Nucleus of the Rat Hypothalamus, Are Regulated during Suckling Endocrinology, February 1, 2001; 142(2): 896 - 906. [Abstract] [Full Text] [PDF]

				A. Kalsbeek, E. Fliers, A. N. Franke, J. Wortel, and R. M. Buijs Functional Connections between the Suprachiasmatic Nucleus and the Thyroid Gland as Revealed by Lesioning and Viral Tracing Techniques in the Rat Endocrinology, October 1, 2000; 141(10): 3832 - 3841. [Abstract] [Full Text] [PDF]

				E. A. Nillni, R. Steinmetz, and O. H. Pescovitz Posttranslational Processing of Progrowth Hormone-Releasing Hormone Endocrinology, December 1, 1999; 140(12): 5817 - 5827. [Abstract] [Full Text]

				E. A. Nillni, C. Vaslet, M. Harris, A. Hollenberg, C. Bjorbak, and J. S. Flier Leptin Regulates Prothyrotropin-releasing Hormone Biosynthesis. EVIDENCE FOR DIRECT AND INDIRECT PATHWAYS J. Biol. Chem., November 10, 2000; 275(46): 36124 - 36133. [Abstract] [Full Text] [PDF]