Pathophysiology
Clinical meaning
The hypothalamic-pituitary axis (HPA) is the master regulatory system controlling virtually all endocrine function. The hypothalamus, located at the base of the brain surrounding the third ventricle, integrates neural and hormonal signals to produce releasing and inhibiting hormones that regulate the anterior pituitary (adenohypophysis) through the hypothalamic-hypophyseal portal venous system. The anterior pituitary produces six major hormones, each regulated by hypothalamic factors through negative feedback loops. (1) TSH (thyroid-stimulating hormone): stimulated by TRH (thyrotropin-releasing hormone); TSH stimulates the thyroid to produce T3 and T4, which feed back negatively on both the hypothalamus (decreasing TRH) and the pituitary (decreasing TSH sensitivity to TRH). (2) ACTH (adrenocorticotropic hormone): stimulated by CRH (corticotropin-releasing hormone); ACTH stimulates cortisol production from the adrenal cortex zona fasciculata; cortisol feeds back negatively on CRH and ACTH. (3) GH (growth hormone): stimulated by GHRH (growth hormone-releasing hormone) and inhibited by somatostatin; GH stimulates IGF-1 production from the liver, which mediates many of GH's growth effects and feeds back negatively. (4) FSH and LH (gonadotropins): stimulated by GnRH (gonadotropin-releasing hormone) in a pulsatile fashion; regulate gonadal function; sex steroids...