Pituitary CRH-binding protein and stress in female mice.
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 4-6h after a 30-minute restraint stress as detected by [(125)I]-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.
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, United States.
Gwen S
GS
Stinnett
Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, United States.
Nicole J
NJ
Westphal
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, United States; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, United States; Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, United States. Electronic address: aseashol@umich.edu.
Audrey F
AF
Seasholtz
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007456:Iodine Isotopes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012727:Sex Characteristics; D013312:Stress, Physiological / Q000502:physiology*; D013997:Time Factors
D002352:Carrier Proteins; D007456:Iodine Isotopes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C067133:corticotropin releasing factor-binding protein; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
CRH-binding protein; Female; LPS; Pituitary; Restraint; Stress