Molecular Development of the Hypothalamic-Pituitary-Adrenal (HPA) Axis

The human hypothalamus lies ventrally to the thalamus and extends from the rostral part of the optic chiasm to the caudal edge of the mamillary bodies. It originates in the alar plate of diencephalon, its sulcus becoming identifiable by the 5th wk of gestation. The hypothalamus is a highly complex organ coordinating central nervous system (CNS) centers and neuroendocrine, metabolic, autonomic nervous and behavioral functions. A system of nerve fibers and portal vessels connects the hypothalamus to the pituitary. The axon terminals of neurons originating in several hypothalamic nuclei, including the supraoptic, the paraventricular, the arcuate, and the ventromedial nucleus, form the median eminence located rostrally to the mamillary bodies. The median eminence communicates with the anterior pituitary via a local portai venous System, which permits the direct hematogenous communication between neurons and endocrine cells. The hypothalamic neurons regulating the function of anterior pituitary corticotrophs are located in the parvocellular part of the paraventricular hypothalamic nucleus. They synthesize the neuropeptides corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP), which, packaged in secretory vesicles, travel the neural axons and reach the median eminence, where they are placed in specifie secretory areas beneath the subplasmalemal actin network ready to be secreted into the portai System.