Regulation of corticotropin-releasing factor receptor messenger ribonucleic acid in rat anterior pituitary.
Adrenalectomy (ADX) leads to a decrease in the number of CRF-binding sites in the rat anterior pituitary (AP). However, the molecular mechanisms of CRF receptor (CRF-R) regulation are unknown. In the present study, we analyzed the effects of ADX on pituitary CRF-R1 messenger RNA (mRNA) levels in vivo and the direct effects of CRF, arginine vasopressin (AVP), and glucocorticoid, the levels of which are altered by ADX, on CRF-R1 mRNA levels in vitro. The mRNA level was determined by Northern blot analysis using a rat brain CRF-R1 complementary RNA probe. The CRF-R1 level in AP fell to 20% of the sham level 1 day after ADX and returned to the sham level after 14 days. In cultured rat AP cells, treatment with CRF, AVP, and dexamethasone led to significant reductions in CRF-R1 mRNA, with maximal inhibition to 32%, 22%, and 37% of control levels, respectively. The time course of CRF-R1 mRNA reduction varied depending on the drug, with effects detectable as early as 1 h after treatment. These findings indicate that elevated portal CRF and AVP levels may contribute to the decrease in CRF-R1 mRNA soon after ADX. A decrease in mRNA levels, in turn, may lead to a decrease in CRF-R1 protein on corticotrophs.
Sakai
K
K
Department of Medicine, Hirosaki University School of Medicine, Japan.
Horiba
N
N
Sakai
Y
Y
Tozawa
F
F
Demura
H
H
Suda
T
T
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001483:Base Sequence; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D007700:Kinetics; D008297:Male; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics*
D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D001127:Arginine Vasopressin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone