Corticotropin-releasing factor up-regulates its own receptor gene expression in corticotropic adenoma cells in vitro.
To investigate the expression of CRF receptor (CRF-R) in human corticotropic adenoma (hCA) cells, we analyzed messenger RNA (mRNA) levels of type-1 CRF-R (CRF-R1). Adenomas were obtained from 10 patients with Cushing's disease. Northern blot analysis using a rat CRF-R1 complementary RNA probe revealed a main hybridization band of 2.7 kilobases in all the hCAs. The CRF-R1 mRNA level significantly increased after 1 h, reached 15-fold the basal level at 8 h, and remained elevated 24 h after the addition of 10 nmol/L CRF in vitro. Dose dependency of the stimulatory effect of CRF was also demonstrated in hCA cells, whereas CRF down-regulated CRF-R1 mRNA levels in rat anterior pituitary (AP) cells. Treatment with dexamethasone or vasopressin decreased the CRF-R1 mRNA level in hCA cells, as observed in rat AP cells. In conclusion, we detected CRF-R1 mRNA in all hCAs tested. The CRF-R1 mRNA level was up-regulated by CRF itself in cultured hCA cells, in contrast to the down-regulation in rat AP cells.
Sakai
Y
Y
Department of Medicine, Hirosaki University School of Medicine, Japan.
Horiba
N
N
Sakai
K
K
Tozawa
F
F
Kuwayama
A
A
Demura
H
H
Suda
T
T
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D015152:Blotting, Northern; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D005938:Glucocorticoids; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011994:Recombinant Proteins; D001127:Arginine Vasopressin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone