Restoration of growth hormone-releasing hormone (GHRH) responsiveness in pituitary GH3 cells by adenovirus-directed expression of the human GHRH receptor

Eunjig Lee, W. Rachel Duan, T. O.M. Kotlar, J. Larry Jameson

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

GH-secreting GH3 cells lack GH-releasing hormone (GHRH) receptors. In this study we used adenoviral vectors to transfer the human GHRH receptor to GH3 cells in an effort to restore GHRH responsiveness. A replication-deficient recombinant adenovirus (AdGHRH-R) was designed to allow cytomegalovirus promoter-driven expression of the GHRH receptor messenger RNA. COS-7 cells and GH-producing GH3 cells infected with AdGHRH-R showed GHRH receptor expression on their membranes and exhibited specific GHRH binding. The addition of GHRH to GH3 cells infected with AdGHRH-R increased cAMP levels, induced cAMP response element-binding protein phosphorylation and restored GH secretory responsiveness. GHRH treatment also caused activation of mitogen-activated-protein kinase, induction of c-fos, stimulation of GH promotor activity, and increased cellular proliferation. These findings indicate that adenoviral vectors carrying human GHRH receptor are useful for in vitro studies of GHRH receptor biology and represent a first step toward the development of gene therapy for dwarfism caused by GHRH receptor mutations.

Original languageEnglish
Pages (from-to)414-420
Number of pages7
JournalEndocrinology
Volume142
Issue number1
DOIs
Publication statusPublished - 2001 Jan 1

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Growth Hormone-Releasing Hormone
Human Growth Hormone
Adenoviridae
Dwarfism
Cyclic AMP Response Element-Binding Protein
COS Cells
Mitogen-Activated Protein Kinases
Cytomegalovirus
Genetic Therapy
somatotropin releasing hormone receptor
Phosphorylation
Cell Proliferation
Hormones
Messenger RNA
Mutation
Membranes

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

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Restoration of growth hormone-releasing hormone (GHRH) responsiveness in pituitary GH3 cells by adenovirus-directed expression of the human GHRH receptor. / Lee, Eunjig; Duan, W. Rachel; Kotlar, T. O.M.; Jameson, J. Larry.

In: Endocrinology, Vol. 142, No. 1, 01.01.2001, p. 414-420.

Research output: Contribution to journalArticle

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