Cited by 33Stress Responses and CortisolNeuropeptides and Animal PhysiologyAdrenal Hormones and Disorders

Pituitary CRH-binding protein and stress in female mice

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Stinnett, Gwen S., Westphal, Nicole J., Seasholtz, Audrey F.·2015·Physiology & Behavior

Abstract

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.

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Crossref · 10.1016/j.physbeh.2015.02.050

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Authors
Stinnett, G. S., Westphal, N. J., & Seasholtz, A. F.
Affiliations
University of Michigan (US)
Corresponding author
Seasholtz, Audrey F.
Venue
Physiology & Behavior
Publisher
Elsevier BV
Published
2015-10
Volume
150
Pages
16-23
ISSN
0031-9384 (ISSN-L)
OpenAlex
W2085518231
Cited by
33
References
59
Citations by year
2026: 4 · 2025: 3 · 2024: 4 · 2022: 5 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 6 · 2016: 2 · 2015: 1
FWCI
2.08
Type
journal article
Language
en
Open access
Locations
  • Physiology & Behavior (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NRSA (048775)
  • NIH (DK42730, DK57660)
  • University of Michigan Medical School
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
CRH-binding protein, corticotropin-releasing factor, anterior pituitary, restraint stress, lipopolysaccharide, hypothalamic-pituitary-adrenal axis, corticosterone release, sex differences, lactotrophs, stress response regulation
MeSH terms
Adrenocorticotropic Hormone, Animals, Carrier Proteins, Corticosterone, Corticotropin-Releasing Hormone, Female, Gene Expression Regulation, Iodine Isotopes, Lipopolysaccharides, Male, Mice, Inbred C57BL, Mice, Transgenic, Pituitary Gland, RNA, Messenger, Sex Characteristics, Stress, Physiological, Time Factors, Mice

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