Acylated ghrelin is not required for the surge in pituitary growth hormone observed in pregnant mice

Peptides. 2015 Mar;65:29-33. doi: 10.1016/j.peptides.2015.01.005. Epub 2015 Jan 30.

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.

Design: 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.

Conclusion: 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.

Keywords: Acylated ghrelin; Ghrelin O-acyltransferase; Growth hormone; Growth hormone secretagogue receptor type 1a; Pregnancy; Unacylated ghrelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Acyltransferases / deficiency
  • Acyltransferases / genetics*
  • Animals
  • Female
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation
  • Ghrelin / genetics*
  • Ghrelin / metabolism
  • Growth Hormone / genetics*
  • Growth Hormone / metabolism
  • Hypothalamus / metabolism
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pituitary Gland / metabolism
  • Pregnancy
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Signal Transduction

Substances

  • Ghrelin
  • Membrane Proteins
  • RNA, Messenger
  • Growth Hormone
  • Acyltransferases
  • Mboat4 protein, mouse