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The hypothalamus is the part of the brain where the activity of the autonomic nervous system and endocrine glands, which directly control various systems of the body, is integrated with input from other centers that give rise to emotions and behavior. The hypothalamus thus serves to ensure that (1) the organism responds appropriately to deviations from various internal set points (including those for temperature, volume, osmolality, satiety, and body fat content); (2) the responses to such deviations from a set point include coordinated activity of the nervous and endocrine systems; and (3) the emotions and behavior being manifested are appropriate for reflex responses being triggered to correct the deviations from internal set points. The following description outlines the integrative function of the hypothalamus in regard to the coordination of endocrine and central nervous system (CNS) responses.

Intravascular volume loss from any cause activates autonomic neural responses, mainly via the sympathetic nervous system to retain fluid and electrolytes, maintain blood pressure through vascular smooth muscle contraction, and maintain cardiac output by increasing heart rate. The effect of these immediate neural responses is reinforced by the activation of several hormonal systems. In response to a decrease in intravascular volume, the renin–angiotensin–aldosterone system (RAAS) is activated and sodium is retained. Additionally, increasing osmolarity triggers thirst and leads to the release of vasopressin (antidiuretic hormone [ADH]) from hypothalamic neurons that end in the posterior pituitary, resulting in free water absorption in the kidney. In short, the body maintains intravascular volume by regulating sodium reabsorption through aldosterone, while it regulates osmolarity by increasing fluid intake (thirst) and free water retention by vasopressin.

Emotions interplay with these systems to coordinate appropriate behavioral and hormonal responses. Fear and pain activate limbic, hypothalamic, and other centers to coordinate defensive (fight-or-flight) and recuperative behaviors, respectively. These emotional responses to various stressors (eg, perceived threat to body, fear) also activate the sympathetic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis, which coordinate the mammalian stress response by preparing the body for “fight and flight” and by mobilizing energy stores. Any kind of stress (eg, physical, mental, metabolic) leads to the release of corticotropin-releasing hormone (CRH) from the hypothalamus and consequent adrenocorticotropin (ACTH; pituitary) and cortisol (adrenal cortex) secretion. For example, starvation leads to the activation of the HPA axis and ultimately a cortisol-mediated increase in gluconeogenesis to maintain basic physiologic functions.

The pituitary gland is the partner of the hypothalamus on the body side of the mind–body interface. Once viewed as the “master gland” in regulating neuroendocrine systems, the pituitary is now known to be a “middle manager” responding to input from both the brain (via the hypothalamus) and the body (via the various peripheral endocrine glands).

The basic framework for hypothalamic–pituitary function is the neuroendocrine axis, a cascade of interacting hormonal products from various regions of the CNS to the hypothalamus, anterior pituitary gland, peripheral endocrine end organs, ...

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