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Regulation of the Ghrelin Gene: Growth Hormone-Releasing Hormone Upregulates Ghrelin mRNA in the Pituitary

Department of Medicine Nippon Medical School, Tokyo 113-8603, Japan

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach. Ghrelin specifically releases GH following intravenous administration, and its GH-releasing activity in vivo is dependent on growth hormone-releasing hormone (GHRH). We previously reported that the expression of the GHS-R gene in the pituitary is developmentally regulated and GHRH infusion increases pituitary levels of GHS-R mRNA. Ghrelin mRNA and peptide have recently been detected in rat and human pituitaries. However, the regulation of the ghrelin gene in the pituitary is unknown. In this study, pituitary levels of ghrelin mRNA were measured with the reverse transcriptase-polymerase chain reaction in male rats at embryonic day (e)18 and postnatal days 1, 10, 30, and 75. The highest concentrations of ghrelin mRNA in the pituitary were observed at e18 and then they declined with age. The infusion of GHRH (10 µg/h, 4h) in freely-moving adult male rats resulted in a 1.9-fold increase in ghrelin mRNA levels relative to control rats (P < 0.05). These data indicated that the expression of the ghrelin gene in the pituitary is developmentally regulated and the pituitary ghrelin/GHS-R signaling system could modulate the regulation of GH secretion by GHRH.