SF-1 and the transcriptional regulation of the human ACTH receptor gene.
The adrenocorticotropin receptor or ACTH-R which is the type 2 among the melanocortin receptor family is almost exclusively expressed in the adrenal cortex, reflecting a high degree of tissue specificity. In human cultured adrenocortical cells, we have previously reported that ACTH in contrast to most of the peptide hormones, is able to up-regulate the number of its own receptors through an increase of the transcriptional activity of the encoding gene. Three putative SF-1 binding sites are present in the sequence of the human ACTH-R gene promoter at -35 (SF-35), -98 (SF-98) and -209 (SF-209). By EMSA studies, we demonstrated that these sites effectively bind SF-1 protein. After transient transfection of H295R cells using a construct containing the first 263 bp upstream of the transcriptional start site, in front of the luciferase gene in the pGL3 vector, we demonstrated the involvement of all three SF-1 sites to confer maximal constitutive activity to a proximal region of the hACTH-R gene promoter. Only SF-35 and SF-98 play a role in cAMP-induced regulation of this gene.
Naville
D
D
INSERM-INRA U418 and Université Claude Bernard, Hôpital Debrousse, Lyon, France.
Penhoat
A
A
Marchal
R
R
Durand
P
P
Bégeot
M
M
D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004586:Electrophoresis; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D009154:Mutation / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D018043:Receptors, Corticotropin / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014162:Transfection / Q000502:physiology
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D018043:Receptors, Corticotropin; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors