title: Dietary sodium modulates mRNA abundance of enzymes involved in pituitary processing of proopiomelanocortin.
abstract: The messenger RNA abundance of proopiome-lanocortin (POMC) is increased in neurointermediate lobe (NIL) of rat pituitary when ingesting a high sodium diet (8%; HSD), as is the plasma concentration of the natriuretic peptide gamma-melanocyte stimulating hormone (gammay-MSH) derived from it. We examined whether the HSD also increases the mRNA abundance in rat NIL of proconvertases 1 and 2 (PC1, PC2), enzymes involved in the processing of POMC into gamma-MSH. PC1 mRNA increased by 40% after two weeks of the HSD and by 84% after three weeks. PC2 mRNA increased by 40% after two weeks and by more than 3 fold after three weeks. These results for PC2 were confined to NIL as shown by in situ hybridization at one and two weeks, and were accompanied by a significant increase in NIL PC2 protein after three weeks of the HSD as measured by immunoblotting. The increases in PC1 and PC2 mRNA abundance were paralleled by an increase in POMC mRNA level in NIL. Plasma gamma-MSH immunoreactivity averaged 35.1 +/- 3.3 fmol/ml in rats on the LSD, but increased to 70.9 +/- 4.8 fmol/ml after 3 weeks of the HSD (p < 0.002 vs LSD). These results confirm that the HSD increases the plasma concentration of gamma-MSH, consistent with a role for it as a circulating natriuretic peptide. The increased NIL expression of PC1 and PC2 in parallel with POMC in response to the HSD suggests that these changes are part of the coordinated response to states of sodium surfeit.
authors.affiliation: Division of Nephrology, Department of Medicine, San Francisco General Hospital and University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: G
authors.initials: G
authors.lastname: Chandramohan
authors.forename: X P
authors.initials: XP
authors.lastname: Ni
authors.forename: J E
authors.initials: JE
authors.lastname: Kalinyak
authors.forename: M H
authors.initials: MH
authors.lastname: Humphreys
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism; D004039:Diet, Sodium-Restricted; D008297:Male; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D045706:Proprotein Convertase 2; D043484:Proprotein Convertases; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013381:Subtilisins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D019825:gamma-MSH / Q000096:biosynthesis
chemical_list: D012333:RNA, Messenger; D019825:gamma-MSH; D011333:Pro-Opiomelanocortin; D043484:Proprotein Convertases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases