REGULATION OF PITUITARY CORTICOTROPIN-RELEASING HORMONE-BINDING PROTEIN MESSENGER-RIBONUCLEIC-ACID LEVELS BY RESTRAINT STRESS AND ADRENALECTOMY

CRH is the primary hypothalamic regulator of the stress response in hi gher organisms, where it acts as the key mediator of ACTH release in t he 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 cortic otrophs suggests a role for CRH-BP in modulation of the stress respons e. To investigate the in vivo role of rat CRH-BP, the regulation of pi tuitary CRH-BP gene expression by acute restraint stress and/or adrena lectomy was examined using ribonuclease protection assays. After restr aint stress, steady-state levels of CRH-BP transcripts increase two to three times over basal level and remain significantly higher than bas al levels for 120 min after the start of restraint. Adrenalectomy decr eases 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 glucocor ticoids play a significant role in this positive regulation. These dat a also suggest that increased CRH-BP levels, in response to stress, ma y modulate the endocrine stress response by providing an additional fe edback mechanism to maintain homeostasis of the hypothalamus-pituitary -adrenal axis.