Hypothalamic-pituitary axis

INTRODUCTION — 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.

The hypothalamic-pituitary axis will be reviewed here. The functions of the hypothalamic and pituitary hormones are discussed separately. (See "Normal menstrual cycle" and "Physiology of gonadotropin-releasing hormone" and "Physiology of growth hormone" and "Thyroid hormone action" and "Thyroid hormone synthesis and physiology".)

OVERVIEW OF HYPOTHALAMIC-PITUITARY FUNCTION — 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. The hypothalamic peptides directly affect the functions of the thyroid gland, the adrenal gland, and the gonads, as well as influencing growth, milk production, and water balance (table 1). 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 small size of hypothalamic hormones 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.

ANATOMY — 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) [1,2]. 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 that connects the paraventricular and supraoptic nuclei, which produce antidiuretic hormone, to nerve terminals in the median eminence and to the posterior pituitary.

The pituitary stalk, which connects the median eminence to the pituitary gland (figure 2), passes through an opening in the dura surrounding the brain. The pituitary gland lies outside the dura. It rests in the sella turcica below the optic chiasm and is divided into anterior and posterior portions, each with distinct embryology, anatomy, and function. The anterior pituitary (or adenohypophysis) arises from Rathke's pouch from the oral cavity, and the posterior pituitary (or neurohypophysis) arises from neural ectoderm at the floor of the forebrain. The pituitary lies almost directly behind the area between the eyes and can be accessed surgically through the back of the nose (the sphenoid bone). It is a distinctly visible structure on magnetic resonance imaging (MRI) scanning.  

BLOOD SUPPLY — Although most hormones circulate systemically and therefore contact all body tissues, the hypothalamic hormones have a special circulation so that they reach their target cells in the pituitary in high concentrations.

Hypothalamus — The terminals of the hypothalamic neurons are in the median eminence, where hormones are released directly into a primary capillary plexus. These capillaries empty into the portal venous circulation, travel down the pituitary stalk, and bathe the anterior pituitary gland in a secondary capillary plexus (figure 3). Thus, the hormones released by the hypothalamic neurons reach their target cells rapidly and in high concentrations before being diluted in peripheral blood. This proximity is crucial for preservation of the pulsatile output of hormones from the hypothalamic neurons. The effect of gonadotropin-releasing hormone (GnRH), as an example, is critically dependent upon its pulsatile release. (See "Physiology of gonadotropin-releasing hormone".)

Anterior pituitary gland — The anterior pituitary lacks a major direct arterial blood supply; it is bathed in a dense capillary network of pituitary portal blood containing both hypothalamic hormones released in the median eminence and the hormones and paracrine and autocrine factors released from the pituitary cells themselves (figure 3). The venous plexus empties into the petrosal sinuses and then into the peripheral circulation via the internal jugular veins. Thus, venous blood in the petrosal sinuses has a relatively high concentration of pituitary hormones and is a useful site to catheterize and sample when assessing pituitary function. Hypotension in the setting of postpartum hemorrhage can lead to infarction of the pituitary gland and hypopituitarism (known as Sheehan syndrome). (See "Causes of hypopituitarism", section on 'Pituitary infarction (Sheehan syndrome)'.)

Posterior pituitary gland — Unlike the anterior pituitary, which does not have nerve terminals, the posterior pituitary contains the axons and nerve terminals of larger neurons that originate in the paraventricular and supraoptic nuclei of the hypothalamus. The posterior pituitary is supplied by the inferior hypophyseal artery and drains into the inferior hypophyseal veins where its products, vasopressin and oxytocin, are released directly into the systemic circulation.

EFFECTS OF PITUITARY STALK SECTION — These anatomic relationships explain the different results of destruction of the pituitary stalk on anterior and posterior pituitary function. Because the pituitary stalk contains the axons of the posterior pituitary neurons, stalk section leads to atrophy and loss of neuron function and, therefore, loss of posterior pituitary hormones. In contrast, the anterior pituitary, although deprived of blood from the median eminence, continues to receive some arterial input from the inferior hypophyseal artery and, therefore, can maintain viability and continue to respond to hypothalamic hormones if high enough concentrations are achieved in peripheral blood.

Serum prolactin concentrations increase after pituitary stalk division because the lactotrophs in the anterior pituitary no longer receive inhibitory signals from the hypothalamus. This phenomenon accounts for the hyperprolactinemia that often is present in patients with nonprolactin-producing tumors that compress the pituitary stalk.

SUMMARY

●Overview of hypothalamic-pituitary function – 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. (See 'Overview of hypothalamic-pituitary function' above.)

●Anatomy – 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). The pituitary stalk, which connects the median eminence to the pituitary gland (figure 2), passes through an opening in the dura surrounding the brain. The pituitary gland lies outside the dura. It rests in the sella turcica below the optic chiasm and is divided into anterior and posterior portions. (See 'Anatomy' above.)

●Blood supply – Although most hormones circulate systemically and therefore contact all body tissues, the hypothalamic hormones have a special circulation so that they reach their target cells in the pituitary in high concentrations (figure 3). The blood supply of the hypothalamus, anterior pituitary, and posterior pituitary are discussed above.