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The Essential Role of Endogenous Ghrelin in Growth Hormone Expression during Zebrafish Adenohypophysis Development

Key Laboratory of Biodiversity and Conservation of Aquatic Organisms (X.L., J.H., W.H., Z.Y.), Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, People’s Republic of China; Graduate University of Chinese Academy of Sciences (X.L., Z.Y.), Beijing 100049, People’s Republic of China; and Key Laboratory of Molecular Biophysics (Z.Y.), Chinese Ministry of Education, Huazhong University of Science and Technology, Wuhan, Hubei 430074, People’s Republic of China

Address all correspondence and requests for reprints to: Zhan Yin, Ph.D., Principal investigator, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei 430072, People’s Republic of China. E-mail: zyin{at}ihb.ac.cn.

Ghrelin, a multifunctional hormone, including potent GH stimulation activity, has been suggested to be important during embryonic development. Expression of ghrelin has been confirmed in the zebrafish pancreas during embryonic stages. Interfering with ghrelin function using two specific antisense morpholino oligonucleotides causes defects during zebrafish embryonic development. In ghrelin morphants the expression of GH was abolished in zebrafish somatotropes, whereas the expression patterns of the other key molecules involved in hypothalamic-pituitary development and distinct pituitary hormones genes remain largely intact at the appropriate time during zebrafish adenohypophysis development. Effective rescue of the ghrelin morphants with exogenous ghrelin mRNA showed that the correct gene had been targeted. Moreover, by analyzing the efficiencies of the ghrelin morphants rescue experiments with various forms of exogenous mutant ghrelin mRNAs, we also demonstrated the essentiality of the form acyl-ghrelin on GH stimulation during zebrafish adenohypophysis development. Our in vivo experiments, for the first time, also provided evidence of the existence of functional obestatin in the C-terminal part of zebrafish proghrelin peptides. Our research here has demonstrated that zebrafish is a unique model for functional studies of endogenous ghrelin, especially during embryonic development.