Modulation of CRF-R1 mRNA in rat anterior pituitary by dexamethasone: correlation with POMC mRNA.
Glucocorticoids have been shown to decrease CRF receptor binding in the anterior pituitary. To determine whether glucocorticoids or CRF peptide modulate CRF-R1 gene expression, CRF-R1 mRNA levels in rat pituitary and brain were measured after administration of a synthetic glucocorticoid, dexamethasone (DEX) or rat/human CRF (r/hCRF), using a sensitive solution hybridization RNase protection assay. DEX (400 micrograms/day) or r/hCRF (100 micrograms/kg/day) was administered twice daily for 5 days to male rats. DEX treatment caused a significant decrease in CRF-R1 mRNA levels in the anterior pituitary. Also, a significant positive correlation was found between CRF-R1 and POMC mRNA levels in the anterior pituitary of the individual animals: levels of both mRNAs were reduced by DEX. However, r/hCRF treatment had no significant effect on CRF-R1 mRNA levels in the anterior pituitary. In extrahypothalamic brain regions, mRNA levels of CRF-R1 did not change following either DEX or r/hCRF administration. Our data suggest that in addition to POMC and CRF genes, CRF-R1 gene may also be subject to negative feedback control by glucocorticoids.
Zhou
Y
Y
Rockefeller University, Laboratory of the Biology of Addictive Disease, New York, NY 10021, USA.
Spangler
R
R
LaForge
K S
KS
Maggos
C E
CE
Ho
A
A
Kreek
M J
MJ
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects; D008297:Male; D009693:Nucleic Acid Hybridization; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D000099052:CRF Receptor, Type 1
C101531:CRF receptor type 2; D005938:Glucocorticoids; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000099052:CRF Receptor, Type 1; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone