Audrey Seasholtz, Ph.D.

My long-standing research interest is the neural and endocrine control of the stress response. The mammalian stress response is mediated in large part by Corticotropin-Releasing Hormone (CRH, also known as CRF), a 41 amino acid peptide. In the neuroendocrine stress axis, hypothalamic CRH controls the release of adrenocorticotropin (ACTH) from the pituitary, which then controls glucocorticoid release from the adrenal gland. Within the brain, CRH acts as a neurotransmitter to control the behavioral, autonomic and immune responses to stress. Dysregulation of the CRH system has been linked to affective disorders, including major depression and anxiety disorders, and to addiction.

Our laboratory is interested in understanding the molecular regulation of the CRH system including the two classes of CRH receptors and the CRH-binding protein, particularly in stress, depression and relapse to addiction. The CRH-binding protein is distinct from the CRH receptors, but binds CRH with an equally high affinity. It appears to play multiple roles in the brain, from inhibiting CRH actions at CRH receptor 1 to enhancing CRH receptor 2 trafficking and activity. We study the mechanisms that regulate the CRH system in health and disease using: 1) transgenic and knockout mouse models for behavioral analyses; 2) in vivo stress and addiction studies; 3) cell culture analysis for biochemical signaling, trafficking and protein-protein interactions; 4) in vitro assays with purified CRH-binding protein and CRH receptors for binding affinity determinations; and 5) molecular cloning for studies on the molecular evolution of CRH-binding protein (structure and function) from insects to humans.