Altered biosynthesis and secretion of pro-opiomelanocortin in the intermediate and anterior pituitary of carboxypeptidase E-deficient, Cpe(fat)/ Cpe(fat)mice.
The biosynthesis and secretion of pro-opiomelanocortin (POMC) was examined in the pituitary of Cpe(fat)/ Cpe(fat)mice, which are deficient in carboxypeptidase E, a sorting receptor for the regulated secretory pathway (Cool D R, Normant E, Shen F S, et al. Cell 1997; 83: 73-83). Dopamine inhibited forskolin-stimulated accumulation of cAMP in the intermediate lobe of Cpe(fat)/ Cpe(fat)mice, showing that their dopamine receptors were fully functional. This result indicates that the elevated, dopamine-insensitive POMC secretion previously observed in the intermediate pituitary of Cpe(fat)/ Cpe(fat)mice was constitutive, rather than due to defective dopamine receptors. Concomitant with the increase in POMC secretion was a twofold increase in POMC mRNA levels and [(35)S]-methionine incorporation into POMC. In the anterior pituitary of Cpe(fat)/ Cpe(fat)mice, a 1.6-fold increase in basal release of POMC was accompanied by a similar increase in [(35)S]-methionine incorporation into POMC, although POMC mRNA levels were unchanged. Thus, the intermediate and anterior pituitary of Cpe(fat)/ Cpe(fat)mice compensate for the constitutive secretion of POMC by upregulating biosynthesis.
Shen
F S
FS
Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Aguilera
G
G
Loh
Y P
YP
D000818:Animals; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000235:genetics*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006720:Homozygote; D008715:Methionine / Q000493:pharmacokinetics; D051379:Mice; D008817:Mice, Mutant Strains; D010902:Pituitary Gland / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013462:Sulfur Radioisotopes
D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D005576:Colforsin; D011333:Pro-Opiomelanocortin; D008715:Methionine; D000242:Cyclic AMP; D002268:Carboxypeptidases; D043423:Carboxypeptidase H; D004298:Dopamine