title: Ghrelin regulates hypothalamic prolyl carboxypeptidase expression in mice.
abstract: Hypothalamic Prolyl carboxypeptidase (PRCP) plays a role in the regulation of energy metabolism by inactivating hypothalamic α-melanocyte stimulating hormone (α-MSH) levels and thus affecting melanocortin signaling. Alpha-MSH production is highly regulated both at transcriptional and posttranslational levels. Here we show that fasting induces a hypothalamic-specific up-regulation of Prcp mRNA and protein levels. Since fasting is characterized by elevated circulating ghrelin levels, we tested the effect of peripheral and central administration of ghrelin, and found that ghrelin increases hypothalamic Prcp mRNA expression. No changes in Prcp mRNA levels were detected in ghrelin knockout mice compared to their controls. Finally, ghrelin effect on PRCP expression was ghrelin receptor-mediated. Altogether our data show that ghrelin is a key regulator of hypothalamic PRCP expression, and up-regulation of PRCP by ghrelin may be an additional mechanism to decrease melanocortin signaling.
authors.affiliation: Program in Integrative Cell Signaling and Neurobiology of Metabolism, New Haven, CT, 06520, USA ; Department of Ob/Gyn & Reproductive Sciences, New Haven, CT, 06520, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Kwon Jeong
authors.forename: Jung
authors.initials: J
authors.lastname: Dae Kim
authors.forename: Sabrina
authors.initials: S
authors.lastname: Diano
keywords: (ARC), Arcuate nucleus; (AgRP), Agouti related peptide; (CTX), Cortex; (DMH), Dorsomedial nucleus; (GHS-R), Growth hormone secretagogue receptor; (Hcrt), Hypocretin; (LH), Lateral hypothalamus; (MCH), Melanin concentrating hormone; (NPY), Neuropeptide Y; (POMC), Proopiomelanocortin; (PRCP), Prolyl carboxypeptidase; (Prcpgt/gt), Prcp-ablated mice; (VMH), Ventromedial nucleus; (α-MSH), α-Melanocyte stimulating hormone; Alpha-melanocyte stimulating hormone; Fasting; Ghrelin; Hypothalamus; Prolyl carboxypeptidase
references.citation: Endocrinology. 2003 Apr;144(4):1301-14
references.pmid: 12639913
references.citation: Diabetes. 1997 Dec;46(12):2119-23
references.pmid: 9392508
references.citation: Diabetes. 2000 Feb;49(2):177-82
references.pmid: 10868932
references.citation: J Clin Invest. 1981 Jan;67(1):210-5
references.pmid: 7451650
references.citation: Diabetes. 1998 Feb;47(2):294-7
references.pmid: 9519731
references.citation: Neuroendocrinology. 1999 Nov;70(5):306-16
references.pmid: 10567856
references.citation: Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Jun 1;66(Pt 6):702-5
references.pmid: 20516604
references.citation: J Med Chem. 2010 Oct 14;53(19):7251-63
references.pmid: 20857914
references.citation: J Clin Invest. 2004 Aug;114(3):357-69
references.pmid: 15286802
references.citation: Endocrinology. 2003 Apr;144(4):1506-12
references.pmid: 12639935
references.citation: Nature. 2000 Oct 19;407(6806):908-13
references.pmid: 11057670
references.citation: Neuroendocrinology. 1992 Dec;56(6):913-20
references.pmid: 1369602
references.citation: Neuroendocrinology. 1999 Dec;70(6):377-83
references.pmid: 10657730
references.citation: Cell. 2001 Feb 23;104(4):531-43
references.pmid: 11239410
references.citation: Nature. 2008 Aug 14;454(7206):846-51
references.pmid: 18668043
references.citation: J Clin Invest. 2009 Aug;119(8):2291-303
references.pmid: 19620781
references.citation: J Comp Neurol. 2001 Jan 15;429(3):469-89
references.pmid: 11116232
references.citation: J Neurosci. 2003 Aug 6;23(18):7143-54
references.pmid: 12904474
references.citation: Am J Physiol Endocrinol Metab. 2012 Jun 15;302(12):E1502-10
references.pmid: 22454290
references.citation: Peptides. 2003 Apr;24(4):597-602
references.pmid: 12860204
references.citation: Nat Neurosci. 2006 Mar;9(3):381-8
references.pmid: 16491079
references.citation: BMC Struct Biol. 2010 Jun 11;10:16
references.pmid: 20540760
references.citation: Endocrinology. 2012 Feb;153(2):683-9
references.pmid: 22202165