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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

Authors
 Eun Jig Lee  ;  W. Rachel Duan  ;  Tom Kotlar  ;  J. Larry Jameson 
Citation
 ENDOCRINOLOGY, Vol.142(1) : 414-420, 2001 
Journal Title
 ENDOCRINOLOGY 
ISSN
 0013-7227 
Issue Date
2001
MeSH
Adenoviridae ; Animals ; COS Cells ; Cell Line ; Cercopithecus aethiops ; Cyclic AMP/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Cytomegalovirus/genetics ; Genetic Vectors ; Growth Hormone/metabolism ; Growth Hormone-Releasing Hormone/pharmacology* ; Humans ; Phosphorylation ; Pituitary Gland ; Prolactin/metabolism ; Promoter Regions, Genetic ; Receptors, Somatotropin/genetics ; Receptors, Somatotropin/physiology* ; Recombinant Proteins/metabolism ; Transfection
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.
Full Text
http://press.endocrine.org/doi/abs/10.1210/endo.142.1.7896
DOI
10.1210/endo.142.1.7896
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Eun Jig(이은직) ORCID logo https://orcid.org/0000-0002-9876-8370
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142125
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