Pituitary CRH-binding protein and stress in female mice

PHYSIOLOGY & BEHAVIOR

卷:150

Article; Proceedings Paper

Stinnett, Gwen S.¹  Westphal, Nicole J.²  Seasholtz, Audrey F.^1,2,3 

[1] Univ Michigan, Mol & Behav Neurosci Inst, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Neurosci Grad Program, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

关键词: CRH-binding protein;    Stress;    Pituitary;    Female;    LPS;    Restraint;   

DOI  :  10.1016/j.physbeh.2015.02.050

来源: Elsevier

【 摘 要 】

The CRH-binding protein (CRH-BP) binds CRH with very high affinity and inhibits CRH-mediated ACTH release from anterior pituitary cells in vitro, suggesting that the CRH-BP functions as a negative regulator of CRH activity. Our previous studies have demonstrated sexually dimorphic expression of CRH-BP in the murine pituitary. Basal CRH-BP expression is higher in the female pituitary, where CRH-BP mRNA is detected in multiple anterior pituitary cell types. In this study, we examined stress-induced changes in CRH-BP mRNA and protein expression in mouse pituitary and assessed the in vivo role of CRH-BP in modulating the stress response. Pituitary CRH-BP mRNA was greater than 200-fold more abundant in females than males, and restraint stress increased pituitary CRH-BP mRNA by 11.8-fold in females and 3.2-fold in males as assessed by qRT-PCR In females, restraint stress increased CRH-BP mRNA levels not only in POMC-expressing cells, but also in PRL-expressing cells. The increase in female pituitary CRH-BP mRNA following stress resulted in significant increases in CRH-BP protein 4-6 h after a 30-minute restraint stress as detected by [I-125]-CRH:CRH-BP cross-linking analyses. Based on this temporal profile, the physiological role of CRH-BP was assessed using a stressor of longer duration. In lipopolysaccharide (LPS) stress studies, female CRH-BP-deficient mice showed elevated levels of stress-induced corticosterone release as compared to wild-type littermates. These studies demonstrate a role for the pituitary CRH-BP in attenuating the HPA response to stress in female mice. (C) 2015 Elsevier Inc. All rights reserved.

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