Functional Anatomy of the Hypothalamus and Pituitary Gland

The hypothalamus is a region of the brain that controls an immense number of bodily functions. It is located in the middle of the base of the brain, and encapsulates the ventral portion of the third ventricle.

The pituitary gland, also known as the hypophysis, is a roundish organ that lies immediately beneath the hypothalamus. In an adult human or sheep, the pituitary is roughly the size and shape of a garbonzo bean.

The image to the right, from the Visible Human Project, shows these anatomical relationships in the Visible Woman.

Careful examination of the pituitary gland reveals that it composed of two distinctive parts:

• The anterior pituitary (adenohypophysis) is a classical gland composed predominantly of cells that secrete protein hormones.
• The posterior pituitary (neurohypophysis) is not really an organ, but an extension of the hypothalamus. It is composed largely of the axons of hypothalamic neurons which extend downward as a large bundle behind the anterior pituitary. It also forms the so-called pituitary stalk, which appears to suspend the anterior gland from the hypothalamus.

A key to understanding the endocrine relationship between hypothalamus and anterior pituitary is to appreciate the vascular connections between these organs. As will be emphasized in later sections, secretion of hormones from the anterior pituitary is under strict control by hypothalamic hormones. These hypothalamic hormones reach the anterior pituitary through the following route:

• A branch of the hypophyseal artery ramifies into a capillary bed in the lower hypothalamus, and hypothalmic hormones destined for the anterior pituitary are secreted into that capillary blood.
• Blood from those capillaries drains into hypothalamic-hypophyseal portal veins. Portal veins are defined as veins between two capillary beds; the hypothalamic-hypophyseal portal veins branch again into another series of capillaries within the anterior pituitary.
• Capillaries within the anterior pituitary, which carry hormones secreted by that gland, coalesce into veins that drain into the systemic venous blood. Those veins also collect capillary blood from the posterior pituitary gland.

Overview of Hypothalamic and Pituitary Hormones

The pituitary gland is often portrayed as the "master gland" of the body. Such praise is justified in the sense that the anterior and posterior pituitary secrete a battery of hormones that collectively influence all cells and affect virtually all physiologic processes.

The pituitary gland may be king, but the power behind the throne is clearly the hypothalamus. As alluded to in the last section, some of the neurons within the hypothalamus - neurosecretory neurons - secrete hormones that strictly control secretion of hormones from the anterior pituitary. The hypothalamic hormones are referred to as releasing hormones and inhibiting hormones, reflecting their influence on anterior pituitary hormones.

Hypothalamic releasing and inhibiting hormones are carried directly to the anterior pituitary gland via hypothalamic-hypophyseal portal veins. Specific hypothalamic hormones bind to receptors on specific anterior pituitary cells, modulating the release of the hormone they produce.

As an example, thyroid-releasing hormone from the hypothalamus binds to receptors on anterior pituitary cells called thyrotrophs, stimulating them to secrete thyroid-stimulating hormone or TSH. The anterior pituitary hormones enter the systemic circulation and bind to their receptors on other target organs. In the case of TSH, the target organ is the thyroid gland.

Clearly, robust control systems must be in place to prevent over or under-secretion of hypothalamic and anterior pituitary hormones.

The following table summarizes the major hormones synthesized and secreted by the pituitary gland, along with summary statements about their major target organs and physiologic effects.

	Hormone	Major target organ(s)	Major Physiologic Effects
Anterior Pituitary	Growth hormone	Liver, adipose tissue	Promotes growth, control of protein, lipid and carbohydrate metabolism
	Thyroid-stimulating hormone	Thyroid gland	Stimulates secretion of thyroid hormones
	Adrenocorticotropic hormone	Adrenal gland (cortex)	Stimulates secretion of glucocorticoids
	Prolactin	Mammary gland	Milk production
	Luteinizing hormone	Ovary and testis	Control of reproductive function
	Follicle-stimulating hormone	Ovary and testis	Control of reproductive function
Posterior Pituitary	Antidiuretic hormone	Kidney	Conservation of body water
	Oxytocin	Ovary and testis	Stimulates milk ejection and uterine contractions

As seen in the table above, the anterior pituitary synthesizes and secreted 6 major hormones. A final point to be made is that individual cells within the anterior pituitary secrete a single hormone (or possibly two in some cases). Thus, the anterior pituitary contains at least six distinctive endocrinocytes.

The cells that secrete thyroid-stimulating hormone do not also secrete growth hormone, and they have receptors for thyroid-releasing hormone, not growth hormone-releasing hormone. The image below is of a section of canine anterior pituitary that was immunologically stained for luteinizing hormone (black stain) and prolactin (purple stain). The unstained cells in the image are those that secrete the other pituitary hormones.

Growth Hormone

Growth hormone, also known as somatotropin, is a protein hormone of about 190 amino acids that is synthesized and secreted by cells called somatotrophs in the anterior pituitary. It is a major participant in control of several complex physiologic processes, including growth and metabolism. Growth hormone is also of considerable interest as a drug used in both humans and animals.

Physiologic Effects of Growth Hormone

A critical concept in understanding growth hormone activity is that it has two distinct types of effects:

• Direct effects are the result of growth hormone binding its receptor on target cells. Fat cells (adipocytes), for example, have growth hormone receptors, and growth hormone stimulates them to break down triglyceride and supresses their ability to take up and accumulate circulating lipids.
• Indirect effects are mediated primarily by a insulin-like growth factor-1 (IGF-1), a hormone that is secreted from the liver and other tissues in response to growth hormone.

Growth is a very complex process, and requires the coordinated action of several hormones. The major role of growth hormone in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. IGF-1 stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth. Growth hormone does seem to have a direct effect on bone growth in stimulating differentiation of chondrocytes.

IGF-1 also appears to be the key player in muscle growth. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.

Control of Growth Hormone Secretion

Production of growth hormone is modulated by many factors, including stress, exercise, nutrition, sleep and growth hormone itself. However, its primary controllers are two hypothalamic hormones and one hormone from the stomach:

• Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.
• Ghrelin is a peptide hormone secreted from the stomach. Ghrelin potently stimulates secretion of growth hormone.

States of growth hormone deficiency provide very visible testaments to the role of this hormone in normal physiology. Such disorders can reflect lesions in either the hypothalamus, the pituitary or in target cells. A deficiency state can result not only from a deficiency in production of the hormone, but in the target cell's response to the hormone.

Clinically, deficiency in growth hormone or receptor defects are as growth retardation or dwarfism. The manifestation of growth hormone deficiency depends upon the age of onset of the disorder and can result from either heritable or acquired disease.

Thyroid-Stimulating Hormone (Thyrotropin)

Thyroid-stimulating hormone, also known as thyrotropin, is secreted from cells in the anterior pituitary called thyrotrophs, finds its receptors on epithelial cells in the thyroid gland, and stimulates that gland to synthesize and release thyroid hormones.

The most important controller of TSH secretion is thyroid-releasing hormone. Thyroid-releasing hormone is secreted by hypothalamic neurons into hypothalamic-hypophyseal portal blood, finds its receptors on thyrotrophs in the anterior pituitary and stimulates secretion of TSH.

The Thyroid and Parathyroid Glands: Introduction and Index

Thyroid hormones affect three fundamental physiologic processes: cellular differentiation, growth, and metabolism. The thyroid gland also produces another hormone called calcitonin, and the parathyroid glands secrete parathyroid hormone. Parathyroid hormone and calcitonin participate in control of calcium and phosphorus homeostasis and have significant effects on bone physiology.

Physiologic Effects of Thyroid Hormones

It is likely that all cells in the body are targets for thyroid hormones. Thyroid hormones have profound effects on many "big time" physiologic processes, such as growth and metabolism.

Metabolism: Thyroid hormones stimulate diverse metabolic activities most tissues, leading to an increase in basal metabolic rate.

• Lipid metabolism: Increased thyroid hormone levels stimulate fat mobilization, leading to increased concentrations of fatty acids in plasma. They also enhance oxidation of fatty acids in many tissues. Finally, plasma concentrations of cholesterol and triglycerides are inversely correlated with thyroid hormone levels.
• Carbohydrate metabolism: Thyroid hormones stimulate almost all aspects of carbohydrate metabolism, including enhancement of insulin-dependent entry of glucose into cells and increased gluconeogenesis and glycogenolysis to generate free glucose.

Parathyroid hormone is the most important endocrine regulator of calcium and phosphorus concentration in extracellular fluid. This hormone is secreted from cells of the parathyroid glands and finds its major target cells in bone and kidney.

Physiologic Effects of Parathyroid Hormone

Parathyroid hormone regulates calcium ion concentration in extracellular fluid, if calcium ion concentrations in extracellular fluid fall below normal; bring them back within the normal range. Parathyroid hormone accomplishes its job by stimulating at least three processes:

• Mobilization of calcium from bone: A well-documented effect of parathyroid hormone is to stimulate osteoclasts to reabsorb bone mineral, liberating calcium into blood.
• Enhancing absorption of calcium from the small intestine: Facilitating calcium absorption from the small intestine would clearly serve to elevate blood levels of calcium. Parathyroid hormone stimulates this process, but indirectly by stimulating production of the active form of vitamin D in the kidney. Vitamin D induces synthesis of a calcium-binding protein in intestinal epithelial cells that facilitates efficient absorption of calcium into blood.
• Suppression of calcium loss in urine: Parathyroid hormone puts a brake on excretion of calcium in urine, thus conserving calcium in blood. This effect is mediated by stimulating tubular reabsorption of calcium.