Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone

Journal of Clinical Investigation

Volumn 114, Issue 3, 2004, Pages 357-369

  Sanchez, Vanesa C ^a   Goldstein, Jorge ^a   Stuart, Ronald C ^a   Hovanesian, Virginia ^a   Huo, Lihong ^b   Munzberg, Heike ^b   Friedman, Theodore C ^c   Bjorbaek, Christian ^b   Nillni, Eduardo A ^a  

^a RHODE ISLAND HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c CHARLES R DREW UNIVERSITY OF MEDICINE AND SCIENCE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FURIN; LEPTIN; MESSENGER RNA; NEUROPEPTIDE; PROHORMONE CONVERTASE 1; PROPROTEIN CONVERTASE 2; PROTEIN; PROTIRELIN; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DIET RESTRICTION; FETUS; GENE EXPRESSION; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HYPOTHALAMUS; IMMUNOHISTOCHEMISTRY; MALE; MEDIAN EMINENCE; MOUSE; NONHUMAN; NORTHERN BLOTTING; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; RADIOIMMUNOASSAY; RAT; REGULATORY MECHANISM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; THALAMUS MIDLINE NUCLEUS; WESTERN BLOTTING;

EID: 4043060941     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI21620     Document Type: Article

References (82)

1. l.Seidah, N.G., and Chretien, M. 1997. Eukaryotic protein processing: endoproteolysis of precursor proteins. Curr. Opin. Biotechnol. 8:602-607.
2. Steiner, D.F. 1998. The proprotein convertases. Curr. Opin. Chem. Biol. 2:31-39.
3. Pricker, L. 1988. Carboxypeptidase E. Annu. Rev. Physiol. 50:309-321.
4. Dong, W., Fricker, L.D., and Day, R. 1999. Carboxypeptidase D is a potential candidate to carry out redundant processing functions of Carboxypeptidase E based on comparative distribution studies in the rat central nervous system. Neuroscience. 89:1301-1317.
5. Eipper, B.A., Stoffers, D.A., and Mains, R.E. 1992. The biosynthesis of neuropeptides: peptide α-amidation. Annu. Rev. Neurosci. 15:57-85.
6. Nillni, E.A., and Sevarino, K.A. 1999. The biology of pro-thyrotropin-releasing hormone-derived peptides. Endocr. Rev. 20:599-648.
7. Schaner, P., Todd, R.B., Seidah, N.G., and Nillni, E.A. 1997. Processing of prothyrotropin releasing hormone by the family of prohormone convertases. J. Biol. Chem. 272:19958-19968.
8. Mains, R.E., and Eipper, B.A. 2000. Proopiomelanocortin (POMC) synthesis and cell-specific processing. In Handbook of physiology. Section 7, The endocrine system. Volume IV, Coping with the environment: neural and endocrine mechanisms. B.S. McEwen, editor. Oxford University Press. Oxford, United Kingdom. 85-101.
9. Benjannet, S., Rondeau, N., Day, R., Chretien, M., and Seidah, N.G. 1991. PC1 and PC2 are proprotein convertases capable of cleaving proopiomelanocortin at distinct pairs of basic residues. Proc. Natl. Acad. Sci. U. S. A. 88:3564-3568.
10. Nillni, H.A., et al. 2000. Leptin regulates prothyrotropin-releasing hormone (proTRH) biosynthesis: evidence for direct and indirect pathways. J. Biol. Chem. 275:36124-36133.
11. Spiegelman, B.M., and Flier, J.S. 2001. Obesity and the regulation of energy balance. Cell. 104:531-543.
12. Schwartz, M.W., Woods, S.C., Porte, D.J., Seeley, R.J., and Baskin, D.G. 2000. Central nervous system control of food intake. Nature. 404:661-671.
13. Zhang, Y., et al. 1994. Positional cloning of the mouse obese gene and its human homologue. Nature. 372:425-432.
14. Pelleymounter, M.A., et al. 1995. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 269:540-543.
15. Halaas, J.L., et al. 1995. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 269:543-546.
16. Campfield, L.A., Smith, F.J., Guisez, Y., Devos, R., and Burn, P. 1995. Recombinant mouse OB protein: evidence for peripheral signal linking adiposity and central neural networks. Science. 269:546-549.
17. Ahima, R.S., et al. 1996. Role of leptin in the neuroendocrine response to fasting. Nature. 382:250-252.
18. Flier, J.S., and Maratos-Flier, E. 1998. Obesity and the hypothalmus: novel peptides for new pathways. Cell. 92:437-440.
19. Seidah, N., et al. 1991. Cloning and primary sequence of a mouse candidate prohormone convertase PC1 homologous to PC2, furin, and Kex2: distinct chromosomal localization and messenger RNA distribution in brain and pituitary compared to PC2. Mol Endocrinol. 5:111-122.
20. Seidah, N.G., et al. 1990. cDNA sequence of two distinct pituitary proteins homologous to Kex2 and furin gene products: tissue-specific mRNAs encoding candidates for pro-hormone processing proteinases [erratum 1990, 9:789]. DNA Cell Biol. 9:415-424.
21. Seidah, N.G., Chretien, M., and Day, R. 1994. The family of substilisin/kexin like pro-protein and prohormone convertase: divergent of shared functions. Biochimie. 76:197-209.
22. Winsky-Sommerer, R., et al. 2000. Regional and cellular localization of the neuroendocrine prohormone convertases PC1 and PC2 in the rat central nervous system. J. Comp. Neurol. 424:439-460.
23. Schafer, M.-H., et al. 1993. Gene expression of prohormone and proprotein convertases in the rat CNS: a comparative in sicu hybridization analysis. J. Neurosci. 13:1258-1279.
24. Nillni, E.A., et al. 1995. ProTRH processing by recombinant PC1. Neurochem. 65:2462-2472.
25. Brakch, N., Galanopoulou, A.S., Patel, Y.C., Boileau, G., and Seidah, N.G. 1995. Comparative proteolytic processing of rat prosomatostatin by the convertases PC1, PC2, furin, PACE4, and PC5 in constitutive and regulated secretory pathways. FEBS Lett. 362:143-146.
26. Coates, L.C., and Birch, N.P. 1998. Differential cleavage of provasopressin by the major molecular forms of SPC3. J. Neurochem. 70:1670-1678.
27. Paquet, L., Massie, B., and Mains, R.E. 1996. Proneuropeptide Y processing in large dense-core vesicles: manipulation of prohormone convertase expression in sympathetic neurons using adenoviruses. J. Neurosci. 76:964-973.
28. Villeneuve, P., Seidah, N.G., and Beaudet, A. 2000. Immunohistochemical evidence for the implication of PC1 in the processing of proneurotensin in rat brain. Neuroreport. 11:3443-3447.
29. Johanning, K., et al. 1998. Specificity of prohormone convertase 2 on proenkephalin and proenkephalin-related substrates. J. Biol. Chem. 273:22672-22680.
30. Dey, A., et al. 2003. Biological processing of the cocaine and amphetamine-regulated transcript precursors by prohormone convertases, PC2 and PC1/3. J. Biol. Chem. 278:15007-15014.
31. Zhu, X., et al. 2002. Disruption of PC1/3 expression in mice causes dwarfism and multiple neuroendocrine peptide processing defects. Proc. Natl Acad. Sci. U. S. A. 99:10293-10298.
32. Furuta, M., et al. 1997. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc. Natl. Acad. Sci. U. S. A. 94:6646-6651.
33. Laurent, V., et al. 2002. Mortality in 7B2 null mice can be rescued by adrenalectomy: involvement of dopamine in ACTH hypersecretion. Proc. Natl. Acad. Sci. U. S. A. 99:3087-3092.
34. Westphal, C.H., et al. 1999. The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease. Cell. 96:689-700.
35. Jackson, R., et al. 1997. Obesity and impaired prohormone processing associated with mutations in the human convertase 1 gene. Nat. Genet. 16:303-306.
36. Challis, B.G., et al. 2002. A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum. Mol. Genet. 11:1997-2004.
37. Naggert, J.K., et al. 1995. Hyperinsulinemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat. Genet. 10:135-142.
38. Nillni, E.; Mulcahy, L., Xie, W., Leiter, E.H., and Wetsel, W.C. 2002. Deficiencies in pro-thyrotropin-releasing hormone (pro-TRH) processing and abnormalities in thermoregulation in Cpefat/fat mice. J. Biol. Chem. 277:48587-48595.
39. de Lange, P., et al. 2001. Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone. Endocrinology. 142:3414-3420.
40. Toni, R., and Lechan, R.M. 1993. Neuroendocrine regulation of thyrotropin-releasing hormone (TRH) in the tuberoinfundibular system. J. Endocrinol. Invest. 16:715-753.
41. Blake, N., Eckland, D., Foster, O., and Lightman, S. 1991. Inhibition of hypothalamic thyrotropin-releasing hormone messenger ribonucleic acid during food deprivation. Endocrinology. 129:2714-2718.
42. Rondeel, J.M., et al. 1992. Effect of starvation and subsequent refeeding on thyroid function and release of hypothalamic thyrotropin-releasing hormone. Neuroendocrinology. 56:348-353.
43. Bornstein, S.R., Torpy, D.J., Chrousos, G.P., Licinio, J., and Engelmann, L. 1997. Leptin levels are elevated despite low thyroid hormone levels in the "euthyroid sick" syndrome. J. Clin. Endocrinol. Metab. 82:4278-4279.
44. Steward, C.A., Horan, T.L., Schuhler, S., Bennett, G.W., and Ebling, F.J. 2003. Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster. Neuroreport. 14:687-691.
45. Choi, Y. H., Hartzell, D., Azain, M.J., and Baile, C.A. 2002. TRH decreases food intake and increases water intake and body temperature in rats. Physiol. Behav. 77:1-4.
46. Légrádi, G., Emerson, C.H., Ahima, R.S., Flier, J.S., and Lechan, R.M. 1997. Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger RNA in neurons of the hypothalamic paraventricular nucleus. Endocrinology. 138:2569-2576.
47. Nillni E.A., Luo, L.G., Jackson, I.M.D., and McMillan, P. 1996. Identification of the thyrotropin-releasing hormone precursor, its processing products, and its coexpression with convertase 1 in primary cultures of hypothalamic neurons: anatomic distribution of PC1 and PC2, Endocrinology. 137:5651-5661.
48. Benjannet, S., et al. 1993. Comparative biosynthesis, post-translational modifications and efficiency of prosegment cleavage of the prohormone convertases PC1 and PC2: glycosylation, sulphation and identification of the intracellular site of prosegment cleavage of PC1 and PC2. Biochem. J. 294:735-743.
49. Zhou, A., and Mains, R.E. 1994. Endoproteolytic processing of proopiomelanocortin and prohormone convertase 1 and 2 neuroendocrine cells overexpressing prohormone convertases 1 or 2. J. Biol. Chem. 269:17440-17447.
50. Vaisse, C., et al. 1996. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not ab/ab mice. Nat. Genet. 14:95-97.
51. Bjørbæk, C., Uotani, S., da Silva, B., and Flier, J.S. 1997. Divergent signaling capacities of the long and short isoforms of the leptin receptor. J. Biol. Chem. 272:32686-32695.
52. Harris, M., et al. 2001. Transcriptional regulation of the thyrotropin-releasing hormone gene by leptin and melanocortin signaling. J. Clin. Invest. 107:111-120.
53. Bates, S.H., et al. 2003. STAT3 signalling is required for lepcin regulation of energy balance but not reproduction. Nature. 421:856-859.
54. Huo, L., Munzberg, H., Nillni, E.A., and Bjorbaek, C. 2004. Role of signal transducer and activator of transcription 3 in regulation of hypothalamic trh gene expression by leptin. Endocrinology. 145:2516-2523.
55. Reidy, S.P., and Weber, J.M. 2002. Accelerated substrate cycling: a new energy-wasting role for leptin in vivo. Am J. Physiol. Endocrinol. Metab. 282:E312-E317.
56. Fricker, L.D., et al. 2000. Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J. Neurosci. 20:639-648.
57. Muller, L., Zhu, X., and Lindberg, I. 1997. Mechanism of the facilitation of PC2 maturation by 7B2: involvement in ProPC2 transport and activation but not folding. J. Cell Biol. 139:625-638.
58. Pu, L.P., Ma, W., Barker, J., and Loh, Y.P. 1996. Differential expression of genes encoding prothyrotropin-releasing hormone (proTRH) and prohormone convertases (PC1 and PC2) in rat brain neurons: implications for differential processing of proTRH. Endocrinology. 137:1233-1241.
59. Nillni, E.A., Sevarino, K.A., and Jackson, I.M.D. 1993. Processing of proTRH to its intermediate products occurs before the packing into secretory granules of transfected AtT20 cells. Endocrinology. 132:1271-1277.
60. Jansen, E., Ayoubi, T.A., Meulemans, S.M., and Van de Ven, W.J. 1997. Cell type-specific protein-DNA interactions at the cAMP response elements of the prohormone convertase 1 promoter. Evidence for additional transactivators distinct from CREB/ATF family members. J. Biol. Chem. 272:2500-2508.
61. Jansen, E., Ayoubi, T.A., Meulemans, S.M., and Van De Ven, W.J. 1997. Regulation of human prohormone convertase 2 promoter activity by the transcription factor EGR-1. Biochem. J. 328:69-74.
62. Bjorbaek, C, et al. 2001. Divergent roles of SHP-2 in ERK activation by leptin receptors. J. Biol. Chem. 276:4747-4755.
63. Duan, H.O., and Simpson-Haidaris, P.J. 2003. Functional analysis of interleukin 6 response elements (IL-6REs) on the human gamma-fibrinogen promoter: binding of hepatic Stat3 correlates negatively with transactivation potential of type II IL-6REs. J. Biol. Chem. 278:41270-41281.
64. Li, Q.-L., et al. 2000. Interactions between the prohormone convertase 2 (PC2) promoter and the thyroid hormone receptor. Endocrinology. 141:3256-3266.
65. Li, Q.L., Jansen, E., Brent, G.A., and Friedman, T.C. 2001. Regulation of prohormone convertase 1 (PC1) by thyroid hormone. Am. J. Physiol. Endocrinol. Metab. 280:E160-E170.
66. Bergen, H.T., Mizuno, T., Taylor, J., and Mobbs, C.V. 1999. Resistance to diet-induced obesity is associated with increased proopiomelanocortin mRNA and decreased neuropeptide Y mRNA in the hypothalamus. Brain Res. 851:198-203.
67. Elmquist, J.K., Bjørbsek, C., Ahima, R.S., Flier, J.S., and Saper, C.B. 1998. Distributions of leptin receptor mRNA isoforms in the rat brain. J. Comp. Neurol 395:535-547.
68. Nillni, E.A., Aird, F., Seidah, N.G.; Todd, R.B., and Koenig, J.I. 2001. Prepro TRH178-199 and two novel peptides (pFQ7 and pSE14) derived from its processing, which are produced in the paravencricular nucleus of the rat hypothalamus, are regulated during suckling. Endocrinology. 142:896-906.
69. Nillni, H.A., Lee, A., Legradi, G., and Lechan, R.M. 2002. Effect of precipitated morphine withdrawal on post-translational processing of prothyrortropin releasing hormone (proTRH) in the ventrolateral column of the midbrain periaqueductal gray. J. Neurochem. 80:874-884.
70. Legradi, G., et al. 1996. Opiate withdrawal increases proTRH gene expression in the venrtolateral column of the midbrain periaqueductal gray. Brain Res. 729:10-19.
71. Gahn, L.G., and Sevarino, K.A. 1996. Preprorhyrotropin-releasing hormone mRNA in the rat central gray is strongly and persistently induced during morphine withdrawal. Neuropeptides. 30:207-212.
72. Arancibia, S., Rage, F., Astier, H., and Tapia-Arancibia, L. 1996. Neuroendocrine and autonomous mechanisms underlying thermoregulation in cold environment. Neuroendocrinology. 64:257-267.
73. Kates, A.L., and Himms-Hagen, J. 1992. Effects of cold acclimation and fasting on thyroxine 5′-deiodinase in brown adipose tissue of ob/ob mice. Proc. Soc. Exp. Biol. Med. 200:495-501.
74. Kates, A.L., and Himms-Hagen, J. 1990. Defective regulation of thyroxine 5′-deiodinase in brown adipose tissue of ob/ob mice. Am. J. Physiol. 258:E7-E15.
75. Rosenbaum, M., Murphy, E.M., Heymsfield, S.B., Matthews, D.E., and Leibeil, R.L. 2002. Low dose leptin adminisrrarion reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J. Clin. Endocrinol. Metab. 87:2391-2394.
76. Garcia, S.I., et al. 2002. Thyrotropin-releasing hormone decreases leptin and mediates the leptin-induced pressor effect. Hypertension. 39:491-495.
77. Garcia, S.I., et al. 2001. Thyrotropin-releasing hormone receptor (TRHR) gene is associated with essential hypertension. Hypertension. 38:683-687.
78. Bruhn, T.O., Rondeel, J.M.M., Bolduc, T.G., Luo, L.-G., and Jackson, I.M.D. 1996. Activation of thyrotropin-releasing hormone gene expression in cultured fetal diencephalic neurons by differentiating agents. Endocrinology. 137:572-579.
79. Benjannet, D.L., et al. 1992. Identification of the type 2 proinsulin processing endopeptidase as PC2, a member of the eukaryotic subtilisin family. J. Biol. Chem. 267:15229-15236.
80. Chomczynski, P., and Sacchi, N. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Biochemistry. 162:156-159.
81. Virca, G.D., Northemann, W., Shiels, B.R., Widera, G., and Broome, S. 1990. Simplified northern blot hybridization using 5% sodium dodecyl sulfate. Biotechniques. 8:370-371.
82. Nillni, E.A., Sevarino, K.A., and Jackson, I.M.D. 1993. Identification of the thyrotropin-releasing hormone prohormone and its pose translational processing in a transfected AtT20 cell line. Endocrinology. 132:1260-1270.