Corticotropin releasing hormone receptors: two decades later.
Hypothalamic corticotropin releasing hormone (CRH) regulates pituitary ACTH secretion and mediates behavioral and autonomic responses to stress, through interaction with type 1 plasma membrane receptors (CRHR1) located in pituitary corticotrophs and the brain. Although the CHRI are essential for ACTH responses to stress, their number in the pituitary gland does not correlate with corticotroph responsiveness, suggesting that activation of a small number of receptors is sufficient for maximum ACTH production. CRH binding and hybridization studies in adrenalectomized, glucocorticoid-treated or stressed rats revealed divergent changes in CRH receptors and CRH1 mRNA in the pituitary, with a reduction in receptor binding but normal or elevated expression of CHR1 mRNA levels. Western blot analysis of CRHR1 protein in pituitary membranes from adrenalectomized rats showed unchanged receptor mRNA levels and increased CRHR1 protein, despite binding down-regulation, suggesting that decreased binding is due to homologous desensitization, rather than reduced receptor synthesis. In contrast, decreased CRH binding following glucocorticoid administration is associated with a reduction in CRHR1 protein, suggesting inhibition of CRH1 mRNA translation. The regulation of CRHR1 translation may involve binding of cytosolic proteins, and a minicistron in the 5'-UTR of the CRHR1 mRNA. It is likely that post-transcriptional regulatory mechanisms that permit rapid changes in CRH receptor activity are important for adaptation of corticotroph responsiveness to continuous changes in physiological demands.
Aguilera
Greti
G
Section of Endocrine Physiology, Develomental Endocrinology Branch, National Institute of Child Health & Human Development, National Institutes of Health, Bethesda, MD 20892, USA. Greti_Aguilera@nih.gov
Nikodemova
Maria
M
Wynn
Peter C
PC
Catt
Kevin J
KJ
D020121:5' Untranslated Regions; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011859:Radiography; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone