Characterization of MCH-gene-overprinted-polypeptide-immunoreactive material in hypothalamus reveals an inhibitory role of pro-somatostatin1-64 on somatostatin secretion.
The melanin-concentrating hormone (MCH) gene encodes two proteins, pro-MCH and MCH-gene-overprinted polypeptide (MGOP), produced through alternative splicing of the primary transcript. Our initial purpose was to characterize the MGOP-immunoreactive material. First, MGOP mRNA was clearly found in rat and mouse hypothalami but Western blot analysis failed to unambiguously identify MGOP in protein extracts. Immunohistochemical experiments with wild-type and MCH gene-null mice demonstrated genuine expression of MGOP confined to the MCH-containing neurons in the lateral hypothalamus area and the presence of an 'MGOP-like' antigen in periventricular nucleus and arcuate nucleus neurons and their area of projection. This suggested a colocalization in somatostatin (SRIF) hypophysiotropic neurons. Further characterization, using SRIF gene-null mice and Western blot analysis with recombinant proteins, revealed that the MGOP-like product was pro-SRIF1-64. The role of pro-SRIF1-64 on fetal hypothalamic neurons was evaluated and a strong tonic inhibitory effect on SRIF secretion was found. These results (i) indicate that MGOP expression is restricted to the MCH neurons in the lateral hypothalamus and that MGOP-like immunoreactivity outside this system corresponds to pro-SRIF1-64, and (ii) provide the first evidence for a negative feedback regulation by pro-SRIF1-64 on SRIF secretion, suggesting new mechanisms by which the pro-region of a neuropeptide precursor may control the regulated secretion of a neuropeptide derived from the same precursor.
Institut de Pharmacologie Moléculaire et Cellulaire, UMR 6097 CNRS, 660 route des Lucioles, Sophia-Antipolis, 06560 Valbonne, France.
Isabelle
I
Allaeys
Karine
K
Bouyer
Catherine
C
Loudes
Annie
A
Faivre-Bauman
Florence
F
Petit
Christine
C
Ortola
Bruno
B
Cardinaud
Jacques
J
Epelbaum
Jean-Louis
JL
Nahon
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D005260:Female; D007031:Hypothalamus / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D011498:Protein Precursors / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013004:Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
C419646:MCH-gene-overprinted-polypeptide; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; C089814:prosomatostatin (29-92); D013004:Somatostatin