title: Dietary sodium intake modulates pituitary proopiomelanocortin mRNA abundance.
abstract: The pituitary prohormone proopiomelanocortin gives rise to melanocortins of alpha, beta, and gamma primary structure in addition to corticotropin. Melanocortins have a variety of actions in mammals, and each is natriuretic. In particular, gamma-melanocyte-stimulating hormone has been shown to mediate reflex natriuresis after acute unilateral nephrectomy. We examined whether this peptide could play a role in longer term adjustments in sodium balance by measuring plasma gamma-melanocyte-stimulating hormone and corticotropin concentrations, as well as pituitary proopiomelanocortin mRNA abundance, in Sprague-Dawley rats ingesting either a low (0.07% NaCl) or high (7.5% NaCl) sodium diet. One week after the high sodium diet, plasma gamma-melanocyte-stimulating hormone concentration was double the value seen in rats on the low sodium diet (158 +/- 5 [SE] versus 76 +/- 9 fmol/mL, P < .001), a change that was accompanied by a fivefold increase in plasma atrial natriuretic peptide concentration but no change in plasma corticotropin. Whole pituitary proopiomelanocortin mRNA abundance, measured with a probe to exon 3 of the rat proopiomelanocortin gene, was significantly increased after 1 week of the high sodium diet compared with the low sodium diet and increased further at 2 and 3 weeks. This increase occurred primarily in the neurointermediate lobe as demonstrated by in situ hybridization; the content of gamma-melanocyte-stimulating hormone immunoreactivity was also increased in this lobe, but not the anterior lobe, after 1 week of the high sodium diet. These results demonstrate that high dietary sodium intake increases neurointermediate lobe proopiomelanocortin mRNA abundance compared with a very low sodium diet and also suggest that proopiomelanocortin is preferentially processed into gamma-melanocyte-stimulating hormone rather than corticotropin. These observations consequently raise the possibility of a role for this peptide hormone system in the adjustments to a high salt diet.
authors.affiliation: Division of Nephrology, San Francisco General Hospital, University of California San Francisco 94143, USA.
authors.forename: H
authors.initials: H
authors.lastname: Mayan
authors.forename: K T
authors.initials: KT
authors.lastname: Ling
authors.forename: E Y
authors.initials: EY
authors.lastname: Lee
authors.forename: E
authors.initials: E
authors.lastname: Wiedemann
authors.forename: J E
authors.initials: JE
authors.lastname: Kalinyak
authors.forename: M H
authors.initials: MH
authors.lastname: Humphreys
mesh_terms: D000818:Animals; D001483:Base Sequence; D015342:DNA Probes; D004305:Dose-Response Relationship, Drug; D017403:In Situ Hybridization; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000097:blood*; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine
chemical_list: D015342:DNA Probes; D012333:RNA, Messenger; D012982:Sodium, Dietary; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones