The hypothalamus can be considered the coordinating center of the endocrine system. It consolidates signals derived from upper cortical inputs, autonomic function, environmental cues such as light and temperature, and peripheral endocrine feedback. In turn, the hypothalamus delivers precise signals to the pituitary gland which then releases hormones that influence most endocrine systems in the body. Specifically, the hypothalamic-pituitary axis directly affects the functions of the thyroid gland, the adrenal gland, and the gonads, as well as influencing growth, milk production, and water balance (table 1) [1-4].
The hypothalamic-pituitary axis will be reviewed here. The functions of the hypothalamic and pituitary hormones are discussed separately. (See "Physiology of the normal menstrual cycle" and "Physiology of gonadotropin-releasing hormone" and "Physiology of corticotropin-releasing hormone" and "Physiology of growth hormone" and "Thyroid hormone action" and "Thyroid hormone synthesis and physiology".)
The hypothalamus is also involved in several important nonendocrine functions such as temperature regulation, the activity of the autonomic nervous system, and control of appetite.
The anatomy and unique blood supply of the hypothalamic-pituitary axis are essential to its function. The hypothalamic hormones are small peptides that are generally active only at the relatively high concentrations achieved in the pituitary portal blood system. Their small size and lack of known binding proteins results in rapid degradation and very low concentrations in the peripheral circulation. However, ectopic production of several of these hormones has been identified, both by normal white blood cells and by chromaffin cell tumors. Peripheral hormone receptors have also been identified, although their physiologic importance is not known.
The hypothalamus is located at the base of the brain, below the third ventricle and just above the optic chiasm and pituitary gland (figure 1) [5,6]. This location can be thought of as the intersection of the cortex, the cerebellum, and the brainstem. Most of the cell bodies of the small neurons containing hypothalamic releasing hormones are located in the tuberal area in the anterior part of the hypothalamus. Afferent pathways to the hypothalamic nuclei arise from the brainstem, thalamus, basal ganglia, cerebral cortex, and olfactory areas. Efferent pathways include the dorsal longitudinal fasciculus connecting the hypothalamus to the brainstem reticular centers, connections to the autonomic nervous system and the thalamus, and the hypothalamo-neurohypophysial tract which connects the paraventricular and supraoptic nuclei, which produce antidiuretic hormone, to nerve terminals in the median eminence and to the posterior pituitary. (See "Chapter 6B: Antidiuretic hormone and water balance".)