Effect of gsp oncogene on somatostatin receptor subtype 1 and 2 mRNA levels in GHRH-responsive GH3 cells.
Growth hormone releasing hormone (GHRH) signals via G protein-coupled receptors (GHRH-R) to enhance intracellular Galphas/adenylyl cyclase/cAMP signaling, which in turn has positive effects on GH synthesis and release, as well as proliferation of the GH-producing cells of the anterior pituitary gland. Some GH-producing pituitary tumors express a constitutively active mutant form of Galphas (gsp oncogene). It has been reported that these tumors are more responsive to octreotide therapy. In this study we used a rat GH-producing cell line (GH3) stably transfected with the human GHRH-R cDNA (GH3-GHRHR cells) as a model to study the effects of gsp oncogene on somatostatin (SRIH) receptor subtype 1 and 2 (sst1 and sst2) mRNA levels. Transient transfection of gsp oncogene in GH3-GHRHR cells for 48 h increased intracellular cAMP levels and GH release. Phosphodiesterase (PDE) 4, sst1 and sst2 mRNA levels were increased by G protein mutation as assessed by real-time RT-PCR. Increased PDE mRNA levels in gsp-transfected cells may be a compensatory mechanism to the constitutive activation of cAMP-dependent pathway by G protein mutation and is consistent with reports of higher PDE expression in human pituitary tumor that express gsp. Our data suggest that higher expression of sst1 and sst2 mRNA induced by the gsp oncogene may be a mechanism by which gsp-positive tumors show a greater response to SRIH. GH3 cells permanently transfected with GHRH-R can be used for in vitro studies of actions of GHRH.
Kim
Eunhee
E
Department of Pharmacology and Institute for Basic Medical Science, Kyunghee University School of Medicine, Seoul, 130-701, Korea.
Sohn
Sookjin
S
Lee
Mina
M
Park
Cheolyoung
C
Jung
Jeechang
J
Park
Seungjoon
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D015282:Octreotide / Q000494:pharmacology; D009857:Oncogenes / Q000502:physiology*; D010903:Pituitary Gland, Anterior; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D018013:Receptors, Neuropeptide / Q000096:biosynthesis; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000096:biosynthesis; D017481:Receptors, Somatostatin / Q000235:genetics*; D014162:Transfection
D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D005576:Colforsin; D003994:Bucladesine; D002772:Cholera Toxin; D013007:Growth Hormone-Releasing Hormone; C093733:somatostatin receptor 2; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D019205:GTP-Binding Protein alpha Subunits, Gs; C048250:somatotropin releasing hormone receptor; D015282:Octreotide