title: Regulation of pituitary corticotropin-releasing hormone-binding protein messenger ribonucleic acid levels by restraint stress and adrenalectomy.
abstract: CRH is the primary hypothalamic regulator of the stress response in higher organisms, where it acts as the key mediator of ACTH release in the hypothalamus-pituitary-adrenal axis. The 37-kDa CRH-binding protein (CRH-BP) is known to bind CRH and antagonize CRH-induced ACTH release in vitro. The expression of this protein in anterior pituitary corticotrophs suggests a role for CRH-BP in modulation of the stress response. To investigate the in vivo role of rat CRH-BP, the regulation of pituitary CRH-BP gene expression by acute restraint stress and/or adrenalectomy was examined using ribonuclease protection assays. After restraint stress, steady-state levels of CRH-BP transcripts increase two to three times over basal level and remain significantly higher than basal levels for 120 min after the start of restraint. Adrenalectomy decreases CRH-BP messenger RNA steady-state levels to 8% of control levels. These results demonstrate that pituitary CRH-BP messenger RNA levels are increased in response to acute restraint stress and that glucocorticoids play a significant role in this positive regulation. These data also suggest that increased CRH-BP levels, in response to stress, may modulate the endocrine stress response by providing an additional feedback mechanism to maintain homeostasis of the hypothalamus-pituitary-adrenal axis.
authors.affiliation: Department of Biological Chemistry, The University of Michigan, Ann Arbor 48109, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: McClennen
authors.forename: D N
authors.initials: DN
authors.lastname: Cortright
authors.forename: A F
authors.initials: AF
authors.lastname: Seasholtz
mesh_terms: D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D015342:DNA Probes; D008297:Male; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D012260:Ribonucleases / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D015342:DNA Probes; D012333:RNA, Messenger; C067133:corticotropin releasing factor-binding protein; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D012260:Ribonucleases; D019696:Peptidylprolyl Isomerase; D003345:Corticosterone