The transcription factor prolactin regulatory element-binding protein mediates prolactin transcription induced by thyrotropin-releasing hormone in GH3 cells.
The prolactin regulatory element-binding protein (PREB) is a transcription factor that regulates prolactin (PRL) promoter activity in the rat anterior pituitary. PRL gene expression and secretion are regulated by various hormones and growth factors, including dopamine, epidermal growth factor, and thyrotropin-releasing hormone (TRH). We examined the effect of TRH on PREB expression in pituitary cells. Western blots probed with a PREB-specific antiserum showed that the relative abundance of PREB in GH3 cells increased on treatment with TRH in a dose-dependent manner. The relative abundance of PREB mRNA also increased in a dose-dependent manner after treatment with TRH. TRH induced the expression of the luciferase reporter protein under the PREB promoter control. We used inhibitors of certain signal transduction pathways to show that TRH-induced PREB induction is sensitive to the protein kinase A (PKA) inhibitor. TRH stimulated the activity of the wild-type PRL promoter, whereas mutation of the PREB core-binding element on the PRL promoter reduced this ability. In summary, we have shown that TRH stimulated PREB expression in GH3 cells via the PKA pathway. PREB can function as a transcriptional regulator of PRL promoter activity and might be involved in TRH-induced PRL gene transcription.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan.
Xiao
X
Yu
Koji
K
Murao
Hitomi
H
Imachi
Junhua
J
Li
Takamasa
T
Nishiuchi
Hiroaki
H
Dobashi
Naohisa
N
Hosomi
Hisashi
H
Masugata
Guo-Xing
GX
Zhang
Hisakazu
H
Iwama
Toshihiko
T
Ishida
D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology*; D011388:Prolactin / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014162:Transfection
D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C485592:Preb protein, rat; D014157:Transcription Factors; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D017868:Cyclic AMP-Dependent Protein Kinases