Figure 1.

HPA axis and endogenous glucocorticoid hormones (CORT). A. The HPA Axis consists of 3 populations of cells and the specialized hormones that each secretes: 1] neurons in the medial parvocellular portion of the hypothalamic paraventricular nucleus (PVN) secrete corticotropin releasing hormone (CRH), 2] endocrine cells (corticotrophs) in the anterior pituitary secrete adrenocorticotropic hormone (ACTH), and 3] endocrine cells primarily in the zona fasciculata of the adrenal cortex secrete the glucocorticoid hormones cortisol and/or corticosterone (CORT). CORT is secreted into the systemic circulation [4] and affects cells throughout the body, including the brain. CORT produces direct negative feedback inhibition of corticotrophs in the anterior pituitary [5] and CRH neurons in the PVN [6]. Activity of the HPA axis is directly and indirectly controlled by various neural activity present throughout the forebrain and brainstem [7]. Direct innervation of the CRH neurons in the PVN includes afferents from the bed nucleus of the stria terminalis (BNST), the dorsomedial hypothalamus (DMH), the ventromedial hypothalamus (VMH), the nucleus tractus solitarius (NTS), and the ventrolateral medulla (VLM). Indirect control includes the medial prefrontal cortex (mPFC), hippocampus (HC), amygdala (Amyg) and septum. B. The principal endogenous glucocorticoid hormones in vertebrates are the closely related steroid molecules (4 carbon ring based structure) cortisol and corticosterone.