The prolactin regulatory element-binding regulates of the 11beta-hydroxylase gene.
Prolactin regulatory element-binding (PREB) protein is a transcription factor not only in pituitary but also adrenal gland. Steroid 11beta-hydroxylase (CYP11B1), a member of the cytochrome p-450 superfamily, is responsible for the last step of glucocorticoid biosynthesis in the adrenal cortices of many kinds of animals. In the present study, we have examined the role of PREB in regulating CYP11B1. CYP11B1 expression was found to be regulated by cAMP, which stimulated the expression of PREB. In addition, PREB induced the expression of the luciferase reporter protein that was under the control of the CYP11B1 promoter. Electrophoretic mobility shift analysis (EMSA) showed that PREB mediates its transcriptional effect by binding to the PREB-responsive cis-element (PRCE) of the CYP11B1 promoter. The knockdown of PREB expression attenuated the effects of cAMP on CYP11B1 expression. In summary, our data showed that in the adrenal gland, PREB regulates the transcription of the CYP11B1 gene via cAMP.
Imachi
Hitomi
H
Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-CHO, Kita-gun, Kagawa 761-0793, Japan.
Murao
Koji
K
Cao
Wen Ming
WM
Muraoka
Tomie
T
Nishiuchi
Takamasa
T
Dobashi
Hiroaki
H
Hosomi
Naohisa
N
Iwama
Hisakazu
H
Ishida
Toshihiko
T
D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D015971:Gene Expression Regulation, Enzymologic; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; C485591:Preb protein, mouse; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000242:Cyclic AMP; D013252:Steroid 11-beta-Hydroxylase