title: Acylated ghrelin is not required for the surge in pituitary growth hormone observed in pregnant mice.
abstract: OBJECTIVE
  Ghrelin is produced by the stomach, hypothalamus and pituitary. It circulates as acylated ghrelin (AG, which stimulates growth hormone (GH) secretion) and unacylated ghrelin (UAG). Acylation is mediated by the enzyme ghrelin O-acyltransferase (GOAT). In mice, pregnancy is associated with a marked increase in circulating pituitary GH. We investigated the role of AG and UAG in the surge of plasma GH concentrations in pregnant mice at the end of pregnancy.
  
  
  METHODS
  Using a mouse model generated on a C57BL/6 background (wild type, WT) in which the GOAT gene has been deleted (KO), we measured plasma AG, UAG and GH concentrations and tissue (stomach, pituitary and hypothalamus) preproghrelin and GOAT mRNA in non-pregnant (NP) and pregnant (P), WT and KO mice.
  
  
  RESULTS
  GOAT deletion was associated with undetectable concentrations of AG. UAG concentrations were similar in all groups. In both WT and KO animals, mean GH concentrations increased 30 to 50 times during pregnancy. There was a tendency toward lower median GH concentrations in KO (301 ng/mL) compared to WT (428 ng/mL) mice (p=0.059). Preproghrelin expression was not affected by GOAT deletion or by pregnancy in the stomach. In contrast, pituitary and hypothalamic ghrelin gene expression were lower in KO-NP and KO-P mice compared to their WT counterparts.
  
  
  CONCLUSIONS
  The complete absence of ghrelin acylation, which is associated with undetectable AG concentrations, does not prevent the marked increase in pituitary GH concentrations observed in pregnant mice, suggesting that AG is not the major mediator of GH secretion during pregnancy.
authors: Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4; University of British Columbia, Vancouver, BC, Canada V6T 1Z4; BC Children's Hospital, Vancouver, BC, Canada V6H 3V4. Electronic address: atrivedi@alumni.ubc.ca.
authors: Arjun
authors: A
authors: Trivedi
authors: Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4.
authors: Sandra
authors: S
authors: Babic
authors: MicroBiome Therapeutics, Broomfield, CO 80021, USA.
authors: Mark
authors: M
authors: Heiman
authors: Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4; University of British Columbia, Vancouver, BC, Canada V6T 1Z4; BC Children's Hospital, Vancouver, BC, Canada V6H 3V4.
authors: William T
authors: WT
authors: Gibson
authors: Child & Family Research Institute, Vancouver, BC, Canada V5Z 4H4; University of British Columbia, Vancouver, BC, Canada V6T 1Z4; BC Children's Hospital, Vancouver, BC, Canada V6H 3V4.
authors: Jean-Pierre
authors: JP
authors: Chanoine
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000235:genetics* / Q000378:metabolism; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010902:Pituitary Gland / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D054439:Ghrelin; D008565:Membrane Proteins; D012333:RNA, Messenger; D013006:Growth Hormone; D000217:Acyltransferases; C526983:Mboat4 protein, mouse
keywords: Acylated ghrelin; Ghrelin O-acyltransferase; Growth hormone; Growth hormone secretagogue receptor type 1a; Pregnancy; Unacylated ghrelin