Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Sep;20(5):465-475.
doi: 10.1080/10253890.2017.1336535. Epub 2017 Jun 14.

Pituitary adenylate cyclase activating polypeptide (PACAP), stress, and sex hormones

S Bradley King  1 , Donna J Toufexis  1 , Sayamwong E Hammack  1
Affiliations
Review

Pituitary adenylate cyclase activating polypeptide (PACAP), stress, and sex hormones

S Bradley King et al. Stress. 2017 Sep.

Abstract

Stressor exposure is associated with the onset and severity of many psychopathologies that are more common in women than men. Moreover, the maladaptive expression and function of stress-related hormones have been implicated in these disorders. Evidence suggests that PACAP has a critical role in the stress circuits mediating stress-responding, and PACAP may interact with sex hormones to contribute to sex differences in stress-related disease. In this review, we describe the role of the PACAP/PAC1 system in stress biology, focusing on the role of stress-induced alterations in PACAP expression and signaling in the development of stress-induced behavioral change. Additionally, we present more recent data suggesting potential interactions between stress, PACAP, and circulating estradiol in pathological states, including PTSD. These studies suggest that the level of stress and circulating gonadal hormones may differentially regulate the PACAPergic system in males and females to influence anxiety-like behavior and may be one mechanism underlying the discrepancies in human psychiatric disorders.

Keywords: Estrogen; PAC1; PTSD; anxiety; bed nucleus of the stria terminalis; sex difference.

PubMed Disclaimer

References

    1. Agarwal A, Halvorson LM, & Legradi G (2005). Pituitary adenylate cyclase activating polypeptide (PACAP) mimics neuroendocrine and behavioral manifestations of stress: Evidence for PKA-mediated expression of the corticotropin-releasing hormone (CRH) gene. Brain research. Molecular brain research, 138(1), 45–57. doi: 10.1016/j.molbrainres.2005.03.016 - DOI - PMC - PubMed
    1. Almli LM, Mercer KB, Kerley K, & Feng H (2013). ADCYAP1R1 genotype associates with post-traumatic stress symptoms in highly traumatized African-American females. American Journal of …. doi: 10.1002/ajmg.b.32145 - DOI - PMC - PubMed
    1. Andero R, Dias BG, & Ressler KJ. (2014). A role for Tac2, NkB, and Nk3 receptor in normal and dysregulated fear memory consolidation. Neuron. Retrieved from http://www.sciencedirect.com/science/article/pii/S0896627314004437 - PMC - PubMed
    1. Bangasser, Curtis, Reyes, Bethea, Parastatidis, Ischiropoulos, … Valentino. (2010). Sex differences in corticotropin-releasing factor signaling and trafficking. Molecular Psychiatry, 15(9), 877–877. doi: 10.1038/mp.2010.89 - DOI - PMC - PubMed
    1. Bangasser DA (2013). Sex differences in stress-related receptors: ″micro″ differences with ″macro″ implications for mood and anxiety disorders. Biology of sex differences, 4(1), 2. doi: 10.1186/2042-6410-4-2 - DOI - PMC - PubMed

MeSH terms

Substances