The hypophysis, or pituitary gland, is a pea-size gland located at the base of the brain (illustration on the right). It is the smallest, but the most important endocrine gland.

The name pituitary originates from the Greek ptuo (to spit) and the Latin pituita (mucus). It was thought that mucus, produced by the brain, was excreted through the nose by the pituitary. The name hypophysis, short for hypophysis cerebri, also derives from the Greek hypo, for under, and physis, for growth. It was in fact considered a sort of appendix or attachment beneath the brain.

The hypophysis sits in a small cavity of the sphenoid bone called the sella turcica,Turkish saddle (illustration below). The floor, the dorsum and the front of the sella are formed by the sphenoid bone: the anterior wall is called the tuberculum sellae and the posterior wall is called dorsum sellae. The lateral walls of the sella are formed by the cavernous sinuses, which contain the internal carotid arteries and the 3rd, 4th and 6th cranial nerves, as well as the first (ophthalmic) and second (maxillary) divisions of the 5th cranial nerve. The 6th nerve runs in the center of the cavernous sinus, whereas the other nerves are more lateral. The roof of the sella is formed by a reflection of the dura, called the diaphragma sellae. From one side it prevents the arachnoid and thus the cerebrospinal fluid from entering the sella; from the other side it separates the pituitary from the overlying optic chiasm. This diaphragm is perforated to allow the pituitary stalk to pass through it. The size and the functionality of the opening are important in protecting the pituitary from transmitted pulsations of the choroid plexus and in protecting the optic fibers against suprasellar extension of an expanding pituitary mass.

The hypophysis weighs approximately 100 mg at birth. It then grows rapidly during childhood to reach an average adult weight of 500 mg toward the end of your twenties. The adult pituitary measures approximately 12 mm in width (the transverse diameter, side to side) and 10 mm in length (the antero-posterior diameter, from front to back). The height is 5.7 mm ( +- 1.7mm) and should never exceed 10 mm. The pituitary increases in size, by 12% to 100%, during pregnancy and lactation due to hypertrophy and hyperplasia of the prolactin-secreting cells.

The pituitary consists of three sections: the anterior lobe, the intermediate lobe and the posterior lobe.

The anterior lobe (or adenohypophysis) is the largest part of the gland, comprising about 75% of the total pituitary volume. The anterior lobe consists of three parts:

1. the pars lateralis (also called pars distalis) is the largest part and contains mainly cells that produce growth hormone (GH) and prolactin (PRL), as well as follicle stimulating hormone (FSH) and luteinizing hormone (LH)
2. the pars medialis contains mainly cells that produce adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH), as well as FSH and LH
3. the pars tuberalis is the upward extension of the pars lateralis. It surrounds the infundibular stem and contains mainly cells that produce TSH, LH, and FSH

The anterior lobe is composed of interlacing cords of large polygonal (many-sided) cells, separated by a rich network of fenestrated capillaries (capillaries with openings in their internal lining, which facilitate the exchange of the hormones). The cytoplasm of these cells contain granules of stored hormones that have different affinities to various dyes. As shown by the hematoxylin and eosin ( H & E ) staining in Figure 4, there are acidophilic ("acid-loving") cells that appear a reddish color, basophilic ("base-loving") cells that appear a bluish color and cells that stain poorly with the dye. These cells are called chromophobes ("color-fearing"). Nowadays, immunocytochemical and electron microscopy techniques have permitted the classification of the adenohypophyseal cells based on the hormone they produce. There are 5 major cell types:

In humans the intermediate lobe is rudimentary, representing less than 1% of the total mass of an adult pituitary gland. It is larger (about 3.5%) during fetal life and in lower vertebrates (such as mice) where it secretes the melanocyte-stimulating hormone (MSH), which brings about skin color changes. It has been traditionally considered a vestigial structure in the humans, meaning it lacks any function. The appendix is another example of a vestigial structure. However, recent findings challenge this notion. The intermediate lobe contains follicles filled with proteinaceous material (similar to those found in the thyroid gland. Their function is unknown.

The posterior lobe (or neurohypophysis) is basically a downward extension of the hypothalamus. The hypothalamus is a thin layer of tissue that forms the floor and the lateral walls of the third ventricle. It extends from the optic chiasm (OC) anteriorly (forward) to the mammillary bodies (MB) posteriorly. The hypothalamus contains large neurons (magnocellular) that aggregate to form the supraoptic and paraventricular nuclei and secrete anti-diuretic hormone (ADH) and oxytocin. It also contains small neruons (parvicellular) that synthesize peptides such as somatostatin, thryotropin-releasing hormone, corticotropin-releasing hormone, and gonadotropin-releasing hormone. The hypothalamic neurons send down unmyelinated fibers that exit from the inferior surface of the hypothalamus, forming a swelling called the median eminence, continue as the infundibular stem, penetrate the sellar diaphragm and terminate in as the neurohypophysis. Thus the neurohypophysis consists of dilated terminals of the neurons of the hypothalamic nuclei, nerve-supporting and nonsecretory cells (pituicytes), capillaries, and neurosecretory materials stored at the nerve endings in the form of granules, called Herring bodies. The infundibular stem plus the pars tuberalis of the anterior hypophysis plus the blood vessels make up what is called the pituitary stalk.

Research has shown that the hormonal activity of the anterior lobe is controlled by chemical messengers traveling from the hypothalamus to the anterior lobe.

In the 1950s, the British neurologist Geoffrey Harris discovered that sectioning of the infundibular stalk, which interrupted the communication between hypothalamus and hypophysis, impaired the function of the hypophysis.

In 1964, chemical agents called releasing factors were found in the hypothalamus; and shown to control the secretion of pituitary hormones.

In 1969 the American endocrinologist Roger Guillemin and colleagues isolated and characterized thyrotropin-releasing factor, which stimulates the secretion of thyroid-stimulating hormone from the pituitary.

In the next few years his group and that of the American physiologist Andrew Victor Schally isolated the luteinizing hormone-releasing factor, which stimulates secretion of both LH and FSH, and somatostatin, which inhibits release of growth hormone. For this work, which proved the connection between brain and the endocrine system, they shared the Nobel Prize in physiology or medicine in 1977.

Human somatostatin was one of the first substances produced for pharmacological use in bacteria by recombinant DNA technology. The presence of the releasing factors in the hypothalamus helped to explain the action of the female sex hormones, estrogen and progesterone, and their synthetic versions contained in oral contraceptives.

• Growth

  The hypophysis plays an important role in regulating body growth. By releasing growth hormone (GH), the hypophysis promotes lengthening of the bones.
  
  The action of GH is meditated by another hormone called insulin-like growth factor-1 (IGF-1), produced mainly by liver and bones. The growth-promoting effect of GH ends at puberty, when sexual hormones (androgens and estrogens) close the cartilage of linear bones.
  
  But the GH action continues in adulthood. In fact GH has also a relevant role in regulating some metabolic pathways, especially mediating protein usage in skeletal muscles. This is the reason why GH has become one of the most used and dangerous medications for body-builders.
  
  GH also acts on heart muscle, and recent studies have shown that GH replacement therapy improves heart performances in patients with GH deficiencies.

• Sexual Development

  
  The adenohypophysis produces two hormones, called luteinizing hormone (LH) and follicle stimulating hormone (FSH) which are required for development and maintenance of the sexual characteristics . LH and FSH begin to be secreted at puberty in a pulsatile fashion.
  
  In women, FSH favors the development of one ovarian follicle at each menstrual cycle, and the production of estradiol by the granulosa cells. LH mediates ovulation (departure of the oocyte from the ovarian follicle) and the production of progesterone by the corpus luteum.
  
  In men, LH stimulates production of testosterone by the Leydig cells of the testis. Testosterone is the main androgen hormone and it is responsible for male sexual development (male hairs, muscles, voice changes at puberty). In this general scenario, it is easy to understand how big is the role of pituitary in sexual life: by gonadotropins, this gland regulates the entire fertile period of woman and the fertility of men. LH stimulates the production of androgen-binding protein (ABP) by the Sertoli cells of the testis. This protein allows high local, near the sperm, concentrations of testosterone, on which the full maturation of the spermatozoa depends.
  
  
  

• Lactation

  The pituitary gland regulates lactation by producing the hormone prolactin. This hormone is responsible for the maintenance of lactation, after the mammary gland has been prepared for milk production by estrogens. During the entire post-partum period prolactin is increased because breast suckling stimulates prolactin production. The high prolactin value is also the reason why women are infertile during this period. In fact, this hormone can inhibit the production of gonadotropins and block follicle maturation in the ovary.

• Metabolism

  The adenohypophysis exerts an important role in several metabolic pathways. The most important hormone the gland produces is called thyrotropin (TSH).
  
  The main role of TSH is to regulate the synthesis and production of thyroid hormone from the thyroid gland. These peripheral hormones play a basic job in our metabolism. In fact, they are important in catabolism, the mechanism by which our body burns calories and produces heat.
  
  Thyroid hormones are also very important in regulating other physiological actions:
  - brain development during fetal period,
  - heart function
  - emotional reactions such as anxiety, nervousness or happiness
  
  Finally, they can interfere in the reproductive system by altering menstrual regularity and libido, or in the skeletal system by regulating bone mass.

• Stress

  The hypophysis can regulate some aspects of the stress. Generally, stress can be defined as an emotional and physiological response to a disagreeable situation.
  
  The pituitary is important in some severe and acute stress situations, during which it produces a hormone called ACTH. ACTH stimulates the adrenal cortex, where it regulates the synthesis and production of cortisol. During severe trauma, burns, illness, fever, hypotension, physical exercises, surgery and hypoglycemia, cortisol production increases. Cortisol supports the body's adaptation to the stress condition, by increasing glucose use, the heart activity or electrolyte exchanges.
  
  Finally, ACTH also exerts a less important function in the adrenal cortex: steroid production. In 1975 scientists identified another peptide: endorphin, which acts in experimental animals as a natural pain reliever in times of stress. Endorphin and ACTH are made as parts of a single large protein, which subsequently splits. This may be the body's mechanism for coordinating the physiological activities of two stress-induced hormones. The same large pro-hormone that contains ACTH and endorphin also contains short peptides called melanocyte-stimulating hormones. These substances are analogous to the hormone that regulates pigmentation in fish and amphibians, but in humans they have no known function.

Two hormones are secreted by the posterior lobe. One of these is the antidiuretic hormone (ADH), vasopressin. Vasopressin stimulates the kidney tubules to absorb water from the filtered plasma that passes through the kidneys and thus controls the amount of urine secreted by the kidneys.

The other posterior pituitary hormone is oxytocin, which causes the contraction of the smooth muscles in the uterus, intestines, and blood arterioles. Oxytocin improves the contractions of the uterine muscles during the final stage of pregnancy to stimulate the expulsion of the fetus, and it also stimulates the ejection of milk from the mammary glands following pregnancy.

• Water Regulation

  The hypophysis plays an important role in regulating body growth. By releasing growth hormone (GH), the hypophysis promotes lengthening of the bones.
  
  The action of GH is meditated by another hormone called insulin-like growth factor-1 (IGF-1), produced mainly by liver and bones. The growth-promoting effect of GH ends at puberty, when sexual hormones (androgens and estrogens) close the cartilage of linear bones.
  
  But the GH action continues in adulthood. In fact GH has also a relevant role in regulating some metabolic pathways, especially mediating protein usage in skeletal muscles. This is the reason why GH has become one of the most used and dangerous medications for body-builders.
  
  GH also acts on heart muscle, and recent studies have shown that GH replacement therapy improves heart performances in patients with GH deficiencies.

• Contractions at Delivery

  
  The adenohypophysis produces two hormones, called luteinizing hormone (LH) and follicle stimulating hormone (FSH) which are required for development and maintenance of the sexual characteristics . LH and FSH begin to be secreted at puberty in a pulsatile fashion.
  
  In women, FSH favors the development of one ovarian follicle at each menstrual cycle, and the production of estradiol by the granulosa cells. LH mediates ovulation (departure of the oocyte from the ovarian follicle) and the production of progesterone by the corpus luteum.
  
  In men, LH stimulates production of testosterone by the Leydig cells of the testis. Testosterone is the main androgen hormone and it is responsible for male sexual development (male hairs, muscles, voice changes at puberty). In this general scenario, it is easy to understand how big is the role of pituitary in sexual life: by gonadotropins, this gland regulates the entire fertile period of woman and the fertility of men. LH stimulates the production of androgen-binding protein (ABP) by the Sertoli cells of the testis. This protein allows high local, near the sperm, concentrations of testosterone, on which the full maturation of the spermatozoa depends.