Pituitary Gland

PITUITARY GLAND

TABLE OF CONTENT
Introduction of Pituitary Gland.
Origin and location of Pituitary Gland.
Anatomy and Histology of the Pituitary Gland
Structure of Pituitary Gland.
Parts of Pituitary Gland.
Hormones sereted from Pituitary Gland.
Diseases found in Pituitary Gland.
Diagrams
Functions of Pituitary Gland.
Conclusion.

Introduction of Pituitary Gland.
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g (0.02 oz.).
It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity (sella turcica) covered by a dural fold (diaphragm sellae).
The pituitary fossa, in which the pituitary gland sits, is situated in the sphenoid bone in the middle cranial fossa at the base of the brain.
The pituitary gland secretes hormones regulating homeostasis, including tropic hormones that stimulate other endocrine glands.
It is functionally connected to the hypothalamus by the median eminence via a small tube called the Pituitary Stalk.
It is considered to be the "master gland".

Anatomy and physiology of the pituitary gland:
The pituitary gland weighs about 0.5 to 1 g and is divided into anterior and posterior lobes. The pituitary gland sits in the sella turcica immediately behind the sphenoid sinus. Cavernous sinuses are located laterally on each side of the sella, inclusive of the internal carotid artery and cranial nerves III, IV, V1, V2 and VI. Magnetic resonance imaging (MRI) is the best method for the visualization of hypothalamic-pituitary anatomy, because the optic chiasm, vascular structures, and tumor extension to cavernous sinuses can be well visualized compared with other imaging techniques
Anterior pituitary hormones are regulated by hypothalamic releasing and inhibitory hormones and negative feedback action of the target glandular hormones at the pituitary and hypothalamic levels ( Table 1 ). Among pituitary hormones, only the secretion of prolactin is increased in the absence of hypothalamic influence, because it is mainly under tonic suppression by dopamine, the main prolactin inhibitory factor. All anterior pituitary hormones are secreted in a pulsatile fashion and tend to follow a diurnal pattern.

Table 1: Relationship Among Hypothalamic, Pituitary, and Feedback Hormones and Target Glands
ACTH, adrenocorticotropic hormone; ADH, antidiuretic hormone; CRH, corticotropin-releasing hormone; E2, estradiol; GHRH, growth hormone–releasing hormone; IGF-1, interleukin growth factor 1; LHRH, luteinizing hormone–releasing hormone; PIF, prolactin release inhibitory factor; SMS, somatostatin; T, testosterone; T3, triiodothyronine; T4, thyroxine; TRH, thyrotropin-releasing hormone.
Antidiuretic hormone (ADH, vasopressin) is produced by the supraoptic and paraventricular nuclei of the hypothalamus and travel in the axons through the pituitary stalk to the posterior pituitary gland. The chief physiologic stimulus of ADH secretion is an increase in serum osmolality and a decrease in plasma volume, resulting in water reabsorption at the level of the distal collecting ducts of the kidneys. Small increments in serum osmolality, more than 290 mOsm/kg, lead to a prompt secretion of ADH.

Origin and location of Pituitary Gland:
The pituitary gland is also called The Hypophysis, is the smallest endocrine gland.
Hypophysis (meaning undergrowth) is so named because of its location below the brain as undergrowth.
This is an unpaired small ovoid gland and is no longer than the end of the little finger.
It is located at the base of the brain and lies below the diencephalon in a depression of basis phenoidboneof the skull called Sella Turcica.
It is a complex structure formed of ectodermic growth of the mouth cavity and down growth of the infandibulum.

Structure of Pituitary Gland:
Structurally, the pituitary gland is divided into a larger frontal region (adenohypophysis) and a smaller posterior region (neurohypophysis).
The gland is connected to a region of the brain called the hypothalamus by the pituitary stalk. Directly above the pituitary gland and in front of the pituitary stalk are the crossing fibers of the optic nerves, called the optic chiasm.
On each side of the pituitary gland is the cavernous sinus. Through each cavernous sinus runs a carotid artery that carries blood to the brain, and important nerves that control eye movements.
Because of the close proximity of the pituitary gland to major intracranial nerves and blood vessels, as well as the vital hormonal control the pituitary gland provides, disorders of the pituitary can cause a wide spectrum of symptoms, both hormonal and neurological.

Pituitary Gland

Parts of Pituitary Gland:
Pituitary gland is divided into 3 parts:
PITUITARY GLAND
Anterior pituitary
(Adenohypophysis)
Posterior pituitary
(Neurohypophysis)
Pars Intermedia

Anterior pituitary (Adenohypophysis):
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland.
The anterior pituitary regulates several physiological processes including stress, growth, and reproduction.
Its regulatory functions are achieved through the secretion of various peptide hormones that act on target organs including the adrenal gland, liver, bone, thyroid gland, and gonads.
The anterior pituitary itself is regulated by the hypothalamus and by negative feedback from these target organs.
Disorders of the anterior pituitary are generally classified by the presence of over- or underproduction of pituitary hormones.
For example, a prolactinoma is a pituitary adenoma that overproduces prolactin. I
n Sheehan's syndrome of postpartum hypopituitarism, the anterior pituitary uniformly malfunctions and underproduces all hormones.
Proper function of the anterior pituitary and of the organs it regulates can often be ascertained via blood tests that measure hormone levels.

Anatomy
The pituitary gland is a pea-sized gland that sits in a protective bony enclosure called the sella turcica. It is composed of three lobes: anterior, intermediate, and posterior. In many animals, these three lobes are distinct. However, in humans, the intermediate lobe is but a few cell layers thick and indistinct; as a result, it is often considered part of the anterior pituitary. In all animals, the fleshy, glandular anterior pituitary is distinct from the neural composition of the posterior pituitary.
The anterior pituitary is composed of multiple parts:
Pars distalis The pars distalis, or "distal part", comprises the majority of the anterior pituitary and is where the bulk of pituitary hormone production occurs. Occasionally, "pars distalis" is incorrectly used as a synonym for the anterior pituitary.[citation needed]
Pars tuberalis The pars tuberalis, or "tubular part", forms a sheath extending up from the pars distalis and wrapping around the pituitary stalk. Its function is poorly understood.
Pars intermedia The pars intermedia, or "intermediate part", sits between the pars distalis and the posterior pituitary and is often very small in humans.

Hormone secretion:
The posterior pituitary as a down growth of the brain, it a neurosecretory organ (Wheater, Burkitt & Daniels, 1987).
The secretion of hormones from the posterior pituitary is controlled directly by neurons in the hypothalamus (Marieb, 2004).
The connecting stalk between the hypothalamus and the lobes of the pituitary gland, the infundibulum, carries the hormones of the posterior pituitary from nuclei in the hypothalamus.
The hypothalmicsupraoptic nuclei manufacture anti-diruetic hormone and the hypothalmicparaventricular nuclei manufacture oxytocin.
These hormones are then stored in pituitary axons until their release is triggered (Marieb, 2004).
The anterior pituitary is a glandular secretory organ (Wheater, Burkitt & Daniels, 1987).
The secretion of hormones from the anterior pituitary is controlled by inhibiting and releasing factors secreted by neurons in the hypothalamus.
These inhibiting and releasing factors are release into a primary capillary plexus where they travel, via portal veins, to a secondary capillary plexus where they stimulate the glandular tissue of the anterior pituitary to release its hormones.
Embryology:
The anterior pituitary arises from an invagination of the oral ectoderm and forms Rathke's pouch. This contrasts with the posterior pituitary, which originates from neuroectoderm.

Major hormones secreted:

Pars Intermedia:
Pars intermedia is the boundary between the anterior and posterior lobes of the pituitary.
It contains three types of cells - basophils, chromophobes, and colloid-filled cysts.
The cysts are the remainder of Rathke’s pouch.
In human fetal life, this area produces melanocyte stimulating hormone or MSH which causes the release of melanin pigment in skin melanocytes (pigment cells).
However, the pars intermedia is normally either very small or entirely absent in adulthood.
In lower vertebrates (fish, amphibians) MSH from the pars intermedia is responsible for darkening of the skin, often in response to changes in background color.
This color change is due to MSH stimulating the dispersion of melanin pigment in dermal (skin) melanophore cells.
Major hormone secreted:
Melanocyte Stimulating Hormone or MSH

Posterior pituitary(Neurohypophysis):
The posterior pituitary (or neurohypophysis) comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Despite its name, the posterior pituitary gland is not a gland, per se; rather, it is largely a collection of axonal projections from the hypothalamus that terminate behind the anterior pituitary gland.
Anatomy:
The posterior pituitary consists mainly of neuronal projections (axons) extending from the supraoptic and paraventricular nuclei of the hypothalamus. These axons release peptide hormones into the capillaries of the hypophyseal circulation. In addition to axons, the posterior pituitaryalso contains pituicytes, specialized glial cells resembling astrocytes.
Classification of the posterior pituitary varies, but most sources include the three regions below:
Pars nervosa Also called the neural lobe or posterior lobe, this region constitutes the majority of the posterior pituitary, and is sometimes (incorrectly) considered synonymous with it. Notable features include Herring bodies and pituicytes.
Infundibular stalk Also known as the infundibulum or pituitary stalk, the infundibular stalk bridges the hypothalamic and hypophyseal systems.

Hormones secreted:
Hormones known classically as posterior pituitary hormones are synthesized by the hypothalamus. They are then stored and secreted by the posterior pituitary into the bloodstream.
Role in disease:
Insufficient secretion of vasopressin underlies diabetes insipidus, a condition in which the body loses the capacity to concentrate urine. Affected individuals excrete as much as 20 liters of dilute urine per day. Oversecretion of vasopressin causes the syndrome of inappropriate antidiuretic hormone (SIADH).

Hormones secreted from Pituitary Gland:
HORMONES SECRETED FROM PITUITARY GLAND
Thyroid Stimulating Hormone (TSH):
Stimulates the thyroid gland to release thyroid hormones.
Control basal metabolic rate and play an important role in growth and maturation.
Affect almost every organ in the body.
Growth Hormone (GH): Principal hormone that regulates growth.
Adrenocorticotropic Hormone (ACTH): Triggers the adrenal glands, which regulate stress response with the release of hormones such as cortisol and aldosterone.
Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH): Control reproduction.
Prolactin (PRL): Stimulates secretion of breast milk.

Melanocyte-stimulating hormone(MSH):They stimulate the production and release of melanin (melanogenesis) by melanocytes in skin and hair
Oxytocin:
it is released in large amounts after distension of the cervix and uterus during labor
after stimulation of the nipples, facilitating birth and breastfeedingreastfeeding.
Recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm, social recognition, pair bonding, anxiety, and maternal behaviors
Vasopressin, also called anti-diuretic hormone (ADH): Promotes water retention.

ThyroidStimulatingHormone(TSH):
Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland
Regulation of thyroid hormone levels:
TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3).TSH production is controlled by thyrotropin-releasing hormone (TRH), which is manufactured in the hypothalamus and transported to the anterior pituitary gland via the superior hypophyseal artery, where it increases TSH production and release. Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary production of TSH, decreasing or inhibiting its release.
The level of thyroid hormones (T3 and T4) in the blood has an effect on the pituitary release of TSH; when the levels of T3 and T4 are low, the production of TSH is increased, and, on the converse, when levels of T3 and T4 are high, TSH production is decreased. This effect creates a regulatory negative feedback loop

The TSH receptor
The TSH receptor is found mainly on thyroid follicular cells.Stimulation of the receptor increases T3 and T4 production and secretion.
Stimulating antibodies to this receptor mimic TSH and cause Graves' disease.
Diagnostic:
Further information: Reference ranges for blood tests.Thyroid hormones
TSH levels are tested in the blood of patients suspected of suffering from excess (hyperthyroidism), or deficiency (hypothyroidism) of thyroid hormone. In general, a standard reference range for TSH for adults is between 0.4 and 5.0 µIU/mL (equivalent to mIU/L), but values vary slightly among labs. The therapeutic target range TSH level for patients on treatment ranges between 0.3 to 3.0 μIU/L.The interpretation depends also on what the blood levels of thyroid hormones (T3 and T4) are.
TSH levels for children normally start out much higher. In 2002, the National Academy of Clinical Biochemistry (NACB) in the United States recommended age-related reference limits starting from about 1.3 to 19 µIU/mL for normal-term infants at birth, dropping to 0.6–10 µIU/mL at 10 weeks old, 0.4–7.0 µIU/mL at 14 months and gradually dropping during childhood and puberty to adult levels, 0.4–4.0 µIU/mL.
The NACB also stated that it expected the normal (95%) range for adults to be reduced to 0.4–2.5 µIU/mL, because research had shown that adults with an initially measured TSH level of over 2.0 µIU/mL had "an increased odds ratio of developing hypothyroidism over the [following] 20 years, especially if thyroid antibodies were elevated"

A TSH assay is now also the recommended screening tool for thyroid disease. Recent advances in increasing the sensitivity of the TSH assay make it a better screening tool than free T4

Growth Hormone (GH):
Growth hormone (GH) is a protein-based peptide hormone. It stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland. Somatotropin refers to the growth hormone produced naturally in animals, whereas the term somatropin refers to growth hormone produced by recombinant DNA technology,and is abbreviated "HGH" in humans.
Growth hormone is used in medicine to treat children's growth disorders and adult growth hormone deficiency. In recent years, growth hormone replacement therapies have become popular in the battle against ageing and obesity. Reported effects on GH-deficient patients (but not on healthy people) include decreased body fat, increased muscle mass, increased bone density, increased energy levels, improved skin tone and texture, increased sexual function, and improved immune system function. At this time, hGH is still considered a very complex hormone, and many of its functions are still unknown.
In its role as an anabolic agent, HGH has been used by competitors in sports since the 1970s, and it has been banned by the IOC and NCAA. Traditional urine analysis could not detect doping with HGH, so the ban was unenforceable until the early 2000s when blood tests that could distinguish between natural and artificial hGH were starting to be developed. Blood tests conducted by WADA at the 2004 Olympic Games in Athens, Greece primarily targeted HGH.

Structure:
The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons. The structure includes four helices necessary for functional interaction with the GH receptor. It appears that, in structure, GH is evolutionarily homologous to prolactin and chorionic somatomammotropin. Despite marked structural similarities between growth hormone from different species, only human and primate growth hormones have significant effects in humans.
Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In particular, a ~ 20 kDa variant originated by an alternative splicing is present in a rather constant 1:9 ratio,while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions.This variant has not been identified, but it has been suggested to coincide with a 22 kDaglycosilated variant of 23 kDa identified in the pituitary gland.Furthermore, these variants circulate partially bound to a protein (growth hormone-binding protein, GHBP), which is the truncated part of the growth hormone receptor, and an acid-labile subunit (ALS).

Functions of GH:
Main pathways in endocrine regulation of growth.
Effects of growth hormone on the tissues of the body can generally be described as anabolic (building up).
Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells.
Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms
Because polypeptide hormones are not fat-soluble, they cannot penetrate sarcolemma.
Thus, GH exerts some of its effects by binding to receptors on target cells, where it activates the MAPK/ERK pathway.
Through this mechanism GH directly stimulates division and multiplication of chondrocytes of cartilage.

GH also stimulates, through the JAK-STAT signaling pathway,the production of insulin-like growth factor (IGF-1, formerly known as somatomedin C), a hormone homologous to proinsulin,
The liver is a major target organ of GH for this process and is the principal site of IGF-1 production. IGF-1 has growth-stimulating effects on a wide variety of tissues.
Additional IGF-1 is generated within target tissues, making it what appears to be both an
endocrine and an autocrine/paracrine hormone.
IGF-1 also has stimulatory effects on osteoblast and chondrocyte activity to promote bone growth.
In addition to increasing height in children and adolescents, growth hormone has many other effects on the body.

Adrenocorticotropic Hormone (ACTH):
Adrenocorticotropic hormone (ACTH), also known as 'corticotropin', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland.
It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with corticotropin-releasing hormone from the hypothalamus).
Its principal effects are increased production and release of corticosteroids and, as its name suggests, cortisol from the adrenal cortex.
Structure:
ACTH consists of 39 amino acids, the first 13 of which (counting from the N-terminus) may be cleaved to form α-melanocyte-stimulating hormone (α-MSH). (This common structure is responsible for excessively tanned skin in Addison's disease.) After a short period of time, ACTH is cleaved into α-melanocyte-stimulating hormone (α-MSH) and CLIP, a peptide with unknown activity in humans.
Human ACTH has a molecular weight of 4,540 atomic mass units (Da).

Function:
ACTH acts through the stimulation of cell surface ACTH receptors. which are located primarily on adrenocortical cells of the adrenal cortex. This results in the synthesis and secretion of gluco- and mineralo-corticosteroids and androgenic steroids. The ACTH receptor is a seven-membrane-spanning G protein-coupled receptor. Upon ligand binding, the receptor undergoes conformation changes that stimulate the enzyme adenylylcyclase, which leads to an increase in intracellular cAMP and subsequent activation of protein kinase A. This ultimately results in stimulation of steroidogenesis.
ACTH acts at several key steps to influence the steroidogenic pathway in the adrenal cortex:
ACTH stimulates lipoprotein uptake into cortical cells. This increases the bio-availability of cholesterol in the cells of the adrenal cortex.
ACTH increases the transport of cholesterol into the mitochondria and activates its hydrolysis.
ACTH Stimulates cholesterol side-chain cleavage enzyme, which makes the rate-limiting step in steroidogenesis.This results in the production of pregnenolone.

Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH):
Luteinizing hormone:
Luteinizing hormone (LH, also known as lutropin) is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone (ICSH),[3] it stimulates Leydig cell production of testosterone.

LH in females:
In sexually-mature females, a surge of LH triggers the completion of meiosis I of the egg and its release (ovulation) in the middle of the cycle;
stimulates the now-empty follicle to develop into the corpus luteum, which secretes progesterone during the latter half of the menstrual cycle.
Women with a severe LH deficiency can now be treated with human LH (Luveris) produced by recombinant DNA technology.
LH in males:
LH acts on the interstitial cells (also known as Leydig cells) of the testes stimulating them to synthesize and secrete the male sex hormone, testosterone. LH in males is also known as interstitial cell stimulating hormone (ICSH).

Normal levels
LH levels are normally low during childhood and, in women, high after menopause. As LH is secreted as pulses, it is necessary to follow its concentration over a sufficient period of time to get a proper information about its blood level.
During the reproductive years typical levels are between 1-20 IU/L. Physiologic high LH levels are seen during the LH surge (v.s.); typically they last 48 hours.

Follicle-stimulating hormone:
Follicle-stimulating hormone (FSH) is a hormone found in humans and other animals.
It is synthesized and secreted by gonadotrophs of the anterior pituitary gland.
FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body.
FSH and Luteinizing hormone (LH) act synergistically in reproduction.
Structure:
FSH is a glycoprotein. Each monomeric unit is a protein molecule with a sugar attached to it; two of these make the full, functional protein. Its structure is similar to those of LH, TSH, and hCG. The protein dimer contains 2 polypeptide units, labeled alpha and beta subunits. The alpha subunits of LH, FSH, TSH, and hCG are identical, and contain 92 amino acids. The beta subunits vary. FSH has a beta subunit of 118 amino acids (FSHB), which confers its specific biologic action and is responsible for interaction with the FSH-receptor. The sugar part of the hormone is composed of fucose, galactose, mannose, galactosamine, glucosamine,andsialic acid, the latter being critical for its biologic half-life. The half-life of FSH is 3–4 hours

FSH in females:
In sexually-mature females, FSH (assisted by LH) acts on the follicle to stimulate it to release estrogens.
FSH produced by recombinant DNA technology (Gonal-f) is available to promote ovulation in women planning to undergo in vitro fertilization (IVF) and other forms of assisted reproductive technology.
FSH in males:
In sexually-mature males, FSH acts on spermatogonia stimulating (with the aid of testosterone) the production of sperm.

Prolactin (PRL):
Prolactin (PRL) also known as luteotropic hormone (LTH) is a protein that in humans is encoded by the PRL gene.
Prolactin is a peptide hormone discovered by Dr. Henry Friesen, primarily associated with lactation. In breastfeeding, the act of an infan suckling the nipple stimulates the production of oxytocin which stimulates the "milk let-down" reflex,which fills the breast with milk via a process called lactogenesis, in preparation for the next feed.
Pituitary prolactin secretion is regulated by neuroendocrine neurons in the hypothalamus, the most important ones being the neurosecretorytuberoinfundibulum (TIDA) neurons of the arcuate nucleus, which secrete dopamine to act on the dopamine-2 receptors of lactotrophs, causing inhibition of prolactin secretion. Thyrotropin releasing factor (thyrotropin-releasing hormone) has a stimulatory effect on prolactin release.
Vasoactive intestinal peptide and peptide histidineisoleucine help to regulate prolactin secretion in humans, but the functions of these hormones in birds can be quite different.

Structure:
Prolactin is a single-chain polypeptide of 198 amino acids with a molecular weight of about 24,000 daltons. Its structure is similar to that of growth hormone and placental lactogen. The molecule is folded due to the activity of three disulfide bonds. Significant heterogeneity of the molecule has been described, thus bioassays and immunoassays can give different results due to differing glycosylation, phosphorylation, sulfation, as well as degradation. The non-glycosylated form of prolactin is the dominant form of prolactin that is secreted by the pituitary gland.
Little prolactin is apparently the result of removal of some amino acids, whereas big prolactin can be the product of interaction of several prolactin molecules.
Pit-1 is a transcription factor that binds to the prolactin gene at several sites to allow for the production of prolactin in the pituitary gland. A key regulator of prolactin production is estrogens that enhance growth of prolactin-producing cells and stimulate prolactin production directly, as well as suppressing dopamine.
Human prolactin receptors are insensitive to mouse prolactin

Melanocyte-stimulating hormone:
The melanocyte-stimulating hormones (collectively referred to as MSH or intermedins) are a class of peptide hormones that in nature are produced by cells in the intermediate lobe of the pituitary gland.
They were first isolated by the Yale professor Aaron B. Lerner.
Synthetic analogs of these naturally occurring hormones have also been developed and researched.
Function:
They stimulate the production and release of melanin (melanogenesis) by melanocytes in skin and hair. MSH signals to the brain have effects on appetite and sexual arousal.
Structure of MSH:
Melanocyte-stimulating hormone belongs to a group called the melanocortins. This group includes ACTH, alpha-MSH, beta-MSH and gamma-MSH; these peptides are all cleavage products of a large precursor peptide called pro-opiomelanocortin (POMC). Alpha-MSH is the most important melanocortin for pigmentation.
The different melanocyte-stimulating hormones have the following amino acid sequences:

The different melanocyte-stimulating hormones have the following amino acid sequences:

Oxytocin:
Oxytocin (pronounced /ˌɒksɨˈtoʊsɪn/) is a mammalian hormone that acts primarily as a neurotransmitter in the brain. Also known as alpha-hypophamine (α–hypophamine), oxytocin has the distinction of being the very first polypeptide hormone to be sequenced and synthesized biochemically by Vincent du Vigneaud et al. in 1953.
Oxytocin is best known for its roles in female reproduction: 1) it is released in large amounts after distension of the cervix and uterus during labor, and 2) after stimulation of the nipples, facilitating birth and breastfeeding. Recent studies have begun to investigate oxytocin's role in various behaviors, including orgasm, social recognition, pair bonding, anxiety, and maternal behaviors.For this reason, it is sometimes referred to as the "love hormone."

Oxytocin is a peptide of 9 amino acids (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly).It acts on certain smooth muscles:
stimulating contractions of the uterus at the time of birth;
stimulating release of milk when the baby begins to suckle.
Oxytocin is often given to prospective mothers to hasten birth. Oxytocin also acts on the nucleus accumbens and amygdala in the brain where it enhances:
bonding between males and females after they have mated;
bonding between a mother and her newborn;
and, in humans, increases the level of one's trust in other people.

Synthesis, storage, and release:
The oxytocin peptide is synthesized as an inactive precursor protein from the OXTgene.This precursor protein also includes the oxytocin carrier protein neurophysin I.
The inactive precursor protein is progressively hydrolyzed into smaller fragments (one of which is neurophysin I) via a series of enzymes.
The last hydrolysis which releases the active oxytocinnonapeptide is catalyzed by peptidylglycine alpha-amidatingmonooxygenase (PAM).
The activity of the PAM enzyme system is dependent upon ascorbate which is a necessary vitamin cofactor. By chance, it was discovered that sodium ascorbate by itself stimulated the production of oxytocin from ovarian tissue over a range of concentrations in a dose-dependent manner.
Many of the same tissues (e.g. ovaries, testes, eyes, adrenals, placenta, thymus, pancreas) where PAM (and oxytocin by default) is found are also known to store higher concentrations of vitamin C.

Neural sources:
In the hypothalamus, oxytocin is made in magnocellularneurosecretory cells of the supraoptic and paraventricular nuclei and is stored in Herring bodies at the axon terminals in the posterior pituitary. It is then released into the blood from the posterior lobe (neurohypophysis) of the pituitary gland. These axons (likely, but dendrites have not been ruled out) have collaterals that innervate oxytocin receptors in the nucleus accumbens.The peripheral hormonal and behavioral brain effects of oxytocin it has been suggested are coordinated through its common release through these collaterals.Oxytocin is also made by some neurons in the paraventricular nucleus that project to other parts of the brain and to the spinal cord.Depending on the species, oxytocin-receptor expressing cells are located in other areas, including the amygdala and bed nucleus of the striaterminalis.
In the pituitary gland, oxytocin is packaged in large, dense-core vesicles, where it is bound to neurophysin I as shown in the inset of the figure; neurophysin is a large peptide fragment of the larger precursor protein molecule from which oxytocin is derived by enzymatic cleavage.
Secretion of oxytocin from the neurosecretory nerve endings is regulated by the electrical activity of the oxytocin cells in the hypothalamus. These cells generate action potentials that propagate down axons to the nerve endings in the pituitary; the endings contain large numbers of oxytocin-containing vesicles, which are released by exocytosis when the nerve terminals are depolarised.

Non-neural sources
Outside the brain, oxytocin-containing cells have been identified in several diverse tissues including the corpus luteum.the interstitial cells of Leydig,theretina,the adrenal medulla,theplacenta,thethymusand the pancreas.The finding of significant amounts of this classically "neurohypophysial" hormone outside the central nervous system raises many questions regarding its possible importance in these different tissues.
Female
Oxytocin is synthesized by corpora lutea of several species, including ruminants and primates. Along with estrogen, it is involved in inducing the endometrial synthesis of prostaglandin F2α to cause regression of the corpus luteum.
Male
The Leydig cells in some species have also been shown to possess the biosynthetic machinery to manufacture testicular oxytocinde novo, specifically, in rats (who can synthesize Vitamin C endogenously), and in guinea pigs who (like humans) require an exogenous source of vitamin C (ascorbate) in their diets.

Structure and relation to vasopressin:
Oxytocin is a peptide of nine amino acids (a nonapeptide).
The sequence is cys– tyr– ile – gln – asn – cys – pro – leu – gly- NH2 (CYIQNCPLG-NH2).
The cysteine residues form a sulfur bridge. Oxytocin has a molecular mass of 1007 daltons.
One international unit (IU) of oxytocin is the equivalent of about 2 micrograms of pure peptide.
The biologically active form of oxytocin, commonly measured by RIA and/or HPLC techniques, is also known as the octapeptide "oxytocin disulfide" (oxidized form), but oxytocin also exists as a reduced dithiolnonapeptide called oxytoceine.
It has been theorized that open chain oxytoceine (the reduced form of oxytocin) may also act as a free radical scavenger (by donating an electron to a free radical); oxytoceine may then be oxidized back to oxytocin via the redox potential of dehydroascorbate <---> ascorbate

The structure of oxytocin is very similar to that of vasopressin (cysteine – tyrosine – phe – gln – asn – cys – pro – arg – gly-NH2), also a nonapeptide with a sulfur bridge, whose sequence differs from oxytocin by 2 amino acids. A table showing the sequences of members of the vasopressin/oxytocinsuperfamily and the species expressing them is present in the vasopressin article. Oxytocin and vasopressin were isolated and synthesized by Vincent du Vigneaud in 1953, work for which he received the Nobel Prize in Chemistry in 1955.
Oxytocin and vasopressin are the only known hormones released by the human posterior pituitary gland to act at a distance. However, oxytocin neurons make other peptides, including corticotropin-releasing hormone (CRH) and dynorphin, for example, that act locally. The magnocellular neurons that make oxytocin are adjacent to magnocellular neurons that make vasopressin, and are similar in many respects.

Industrial use of drug:
Oxytocin can be administered to bovine animals in order to increase the production of dairy milk.
Misuse of drug:
Reports exist of hundreds of girls being kidnapped from across India and brought to Sodhawas and Geerwar villages in Alwar district of Rajasthan, where they are given oxytocin injections to hasten their puberty and pushed into prostitution. The kidnapped girls have reportedly been as young as six-month-old babies. They are raised by the villagers as their own daughters

Vasopressin:Vasopressin is a peptide of 9 amino acids (Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly). It is also known as arginine vasopressin (AVP) and the antidiuretic hormone (ADH).
Vasopressin acts on the collecting ducts of the kidney to facilitate the reabsorption of water into the blood. This it acts to reduce the volume of urine formed (giving it its name of antidiuretic hormone).
A deficiency of vasopressin or
inheritance of mutant genes for its receptor (called V2)
leads to excessive loss of urine, a condition known as diabetes insipidus. The most severely-afflicted patients may urinate as much as 30 liters (almost 8 gallons!) of urine each day. The disease is accompanied by terrible thirst, and patients must continually drink water to avoid dangerous dehydration.
Another type of receptor for vasopressin (designated V1a) is found in the brain, e.g., in voles and mice (rodents) and in primates like monkeys and humans.
Male prairie voles (Microtuspinetorum) and marmoset monkeys
have high levels of the V1a receptor in their brains,
tend to be monogamous, and
help with care of their young.

Male meadow voles (Microtusmontanus) and rhesus monkeys
have lower levels of the V1a receptor in their brains,
are promiscuous, and
give little or no help with the care of their young.
Meadow voles whose brains have been injected with a vector causing increased expression of the V1a receptor become more like prairie voles in their behavior. (See Lim, M. M. et al., Nature, 17 June 2004.)
The level of expression of the V1a receptor gene is controlled by a "microsatellite" region upstream (5') of the ORF. This region contains from 178 to 190 copies of a repeated tetranucleotide (e.g., CAGA). Prairie voles have more copies of the repeat than meadow voles, and they express higher levels of the receptor in the parts of the brain associated with these behaviors. A similar microsatellite region is present in the pygmy chimpanzee or bonobo (Pan paniscus) but is much shorter in the less-affectionate common chimpanzee (Pan troglodytes).
Changes in the regulatory region of the human gene for the V1a receptor have been linked to autism.

Control:
Vasopressin is secreted from the posterior pituitary gland in response to reductions in plasma volume, in response to increases in the plasma osmolality, and in response to cholecystokinin by the small intestine
Secretion in response to reduced plasma volume is activated by pressure receptors in the veins. atria, and carotids.
Secretion in response to increases in plasma osmotic pressure is mediated by osmoreceptors in the hypothalamus.
Secretion in response to increases in plasma cholecystokininis mediated by an unknown pathway.
The neurons that make AVP, in the hypothalamic supraoptic nuclei (SON) and paraventricular nuclei (PVN), are themselves osmoreceptors, but they also receive synaptic input from other osmoreceptors located in regions adjacent to the anterior wall of the third ventricle. These regions include the organumvasculosum of the lamina terminalis and the subfornical organ.
Many factors influence the secretion of vasopressin:
Ethanol(alcohol) acts as an antagonist for AVP in the collecting ducts of the kidneys, which prevents aquaporins from binding to the collecting ducts, and prevents water reabsorption.
Angiotensin II may stimulate the secretion of AVP.

Secretion:
The main stimulus for secretion of vasopressin is increased osmolality of plasma. Reduced volume of extracellular fluid also has this effect, but is a less sensitive mechanism.
The AVP that is measured in peripheral blood is almost all derived from secretion from the posterior pituitary gland (except in cases of AVP-secreting tumours). However there are two other sources of AVP with important local effects:
Vasopressin is produced in the PVN and SON and travels down the axons through the infundibulum within neurosecretory granules that are found within Herring bodies, localized swellings of the axons and nerve terminals. These carry the peptide directly to the posterior pituitary gland, where it is stored until released into the blood.
Vasopressin is also released into the brain by several different populations of smaller neurons
Receptors
Below is a table summarizing some of the actions of AVP at its three receptors, differently expressed in different tissues and exerting different actions:

Structure and relation to oxytocin:
Chemical structure of argipressin
The vasopressins are peptides consisting of nine amino acids (nonapeptides). (NB: the value in the table above of 164 amino acids is that obtained before the hormone is activated by cleavage). The amino acid sequence of arginine vasopressin is Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly, with the cysteine residues forming a sulfur bridge. Lysine vasopressin has a lysine in place of the arginine.
The structure of oxytocin is very similar to that of the vasopressins: It is also a nonapeptide with a disulfide bridge and its amino acid sequence differs at only two positions (see table below). The two genes are located on the same chromosome separated by a relatively small distance of less than 15,000 bases in most species. The magnocellular neurons that make vasopressin are adjacent to magnocellular neurons that make oxytocin, and are similar in many respects. The similarity of the two peptides can cause some cross-reactions: oxytocin has a slight antidiuretic function, and high levels of AVP can cause uterine contractions.
Here is a table showing the superfamily of vasopressin and oxytocinneuropeptides:

Diseases found in Pituitary Gland:
The most common problem with the pituitary is the development of a tumor.
While most are benign, they can produce excessive amounts of a specific pituitary
hormone, crowd out the production of other hormones, and compress surrounding tissues.
Blood vessels and the optic nerves are in close proximity to the pituitary gland. Pressure from a tumor can cause headaches, visual disturbances, loss of vision, fatigue, weakness, and seizures, as well as a host of signs and symptoms related to diminished hormone production.
Other pituitary disorders can arise from inherited genetic mutations, be congenital, be due to trauma or an impaired blood supply, due to surgical or radiation treatment of a previous pituitary disorder, due to a malignant tumor (rare), or be due to causes that are not yet well understood.
The hormone deficiencies and excesses from these disorders can produce a variety of symptoms depending on which hormones and target tissues are affected.
When the hypothalamus is dysfunctional, pituitary hormone production is often affected.
TSH in turn stimulates thyroid hormone production by the thyroid gland.

Excess or deficient hormone production by the pituitary may also occur if the glands “downstream” from it are dysfunctional. For example, normally the hypothalamus detects thyroid hormone deficiency in the blood and stimulates the pituitary to produce TSH.
If the thyroid gland is dysfunctional and cannot produce adequate amounts, then blood thyroid hormone levels will remain below normal even though the hypothalamus and pituitary are promoting production..
Common Pituitary Disorders:
Rare Pituitary Disorders:
Acromegaly and Gigantism
Cushing’s Disease
Diabetes Insipidus
Nelson’s Syndrome
Kallman’s Syndrome
Pituitary Tumors
Growth Hormone Deficiency
Hypopituitarism
Empty Sella Syndrome

Examples of Common Pituitary Disorders:
Pituitary Tumors:may be hormone-secreting or non-secreting; most are benign; may cause visual disturbances and headaches as they grow and compress surrounding tissues; often results in excessive amounts of one pituitary hormone and decreases in others.
Signs and symptoms: Pituitary tumors may manifest with signs and symptoms related to pituitary hypofunction, specific hormone(s) hypersecretion, and/or mass effect. Impingement on the chiasm or its branches by a pituitary tumor may result in visual field defects; the most common is bitemporalhemianopsia Lateral extension of the pituitary mass to the cavernous sinuses may result in diplopia, ptosis, or altered facial sensation.Among the cranial nerves, the third nerve is the most commonly affected. There is no specific headache pattern associated with pituitary tumors and, in some patients, the headache is unrelated to pituitary adenoma.
Treatment:The goals for treatment of a pituitary tumor include reduction or complete removal of the tumor, elimination of mass effect, if present, normalization of hormone hypersecretion, and restoration of normal pituitary function. Some patients, especially those with large tumors, may require several therapeutic modalities, including medical, surgical, and radiation therapies

Growth hormone deficiency: The effects of growth hormone deficiency vary depending on the age at which they occur. In children, growth failure and short stature are the major manifestations of GH deficiency, with common causes including genetic conditions and congenital malformations. It can also cause delayed sexual maturity. In adults, deficiency is rare,with the most common cause a pituitary adenoma, and others including a continuation of a childhood problem, other structural lesions or trauma, and very rarely idiopathic GHD
Treatment: With exogenous GH is indicated only in limited circumstances and needs regular monitoring due to the frequency and severity of side-effects
Hypopituitarism: from a variety of causes including tumors, trauma, decreased pituitary blood supply, infection, sarcoidosis, an autoimmune process, radiation, surgical removal of the pituitary, or a side effect of pituitary surgery; results in a general decrease in pituitary hormone production.
Treatment:
Treatment of hypopituitarism is threefold: removing the underlying cause, treating the hormone deficiencies, and addressing any other repercussions that arise from the hormone deficiencies

Causes:

Empty Sella Syndrome : In empty sella syndrome, the sella turcica (the bony structure at the base of the brain that houses the pituitary gland) enlarges, but the pituitary remains normal-sized or shrinks.
People with empty sella syndrome have a defect in the tissue barrier that normally keeps the cerebrospinal fluid around the brain separate from the sella turcica. As a result, cerebrospinal fluid puts increased pressure on the pituitary gland and the walls of the sella turcica. The sella turcica may enlarge, and the pituitary gland may shrink.
Empty sella syndrome occurs most often in middle-aged women who are overweight and who have high blood pressure. Less commonly, the condition occurs after pituitary surgery, radiation therapy, or infarction (death) of a pituitary tumor.
Symptoms:The empty sella syndrome may produce no symptoms at all and seldom produces serious symptoms. About half of those affected have headaches, and some people have high blood pressure as well. In rare cases, there is leaking of the cerebrospinal fluid from the nose or problems with vision.
Treatment: Unless the syndrome results in other medical problems, treatment for endocrine dysfunction associated with pituitary malfunction is symptomatic and supportive. In some cases, surgery may be needed.

Examples of Rare Pituitary Disorders:
Acromegaly and Gigantism:excess growth hormone production, usually due to a tumor; when it occurs in childhood, it causes gigantism associated with excessive bone growth and abnormally tall stature; in adults, it causes acromegaly, with increases in bone thickness, coarsened facial features, enlarged hands and feet, carpal tunnel syndrome, headaches, sweating, sleep apnea, fatigue, and hypertension.
Treatment:
Stopping or reducing the overproduction of growth hormone is not easy; thus, doctors may need to use a combination of surgery, radiation therapy, and drug therapy.
Example:Vikas Kumar "Vicky" Uppal (1986 – June 30, 2007) was a native and resident of India, said to be his country's tallest man until his death.
On 12 January 2004, The Tribune reported him to be 8 ft 3 in (2.51 m) tall and still growing, being in his late teens.On 10 June 2005, rediff.com reported him to be 8 ft 10 in (2.69 m) tall.

Cushing’s Disease:Cushing’s syndrome symptoms caused by a pituitary tumor that produces excess ACTH and leads to excess exposure to the adrenal gland hormone cortisol;
symptoms vary but include: upper body obesity, a rounded face, thin skin, pink streaks on the abdomen, muscular weakness, osteoporosis, high blood sugar, and high blood pressure
Treatment :depends on whether the problem is in the adrenal glands, the pituitary gland, or elsewhere. Surgery or radiation therapy may be needed to remove or destroy a pituitary tumor. Tumors of the adrenal gland (usually adenomas) can often be removed surgically. Both adrenal glands may have to be removed if these treatments are not effective or if no tumor is present.
Diabetes Incipidus:Central diabetes insipidus is a lack of antidiuretic hormone that causes excessive production of very dilute urine (polyuria).
Central diabetes insipidus has several causes, including a brain tumor, tuberculosis, a brain injury or surgery, and some forms of other diseases.
The main symptoms are excessive thirst and excessive urine production.
The diagnosis is based on urine tests, blood tests, and a water deprivation test.
People with central diabetes insipidus usually are given the drugs vasopressin or desmopressin as a nasal spray.

Treatment: Vasopressin or desmopressin (a modified form of vasopressin) may be taken as a nasal spray several times a day. The dose is adjusted to maintain the body's water balance and a normal urine output. Taking too much of these drugs can lead to fluid retention, swelling, and other problems
Nelson’s Syndrome: may result when both adrenal glands are removed as part of the treatment for Cushing’s Disease; a pituitary tumor develops that produces ACTH .
Symptoms: cause darkening of the skin due to increased production of melanocyte stimulating hormone (MSH) disturbances, and delayed growth.
Treatment:Pituitary surgery is performed in some cases. The risk can also be minimized by pituitary irradiation.
Kallman’s Syndrome: deficient release of GnRH (gonadotropin-releasing hormone) leads to lack of FSH and LH production; causes delayed or absent puberty; associated with no sense of smell; occurs only in males.

Functions of Pituitary Gland:
The pituitary is a small, bean-shaped gland located below the brain in the skull base in an area called the pituitary fossa, or sella turcica.
Weighing less than one gram, the pituitary gland is often called the "master gland" since it controls the secretion of hormones.
Hormones have a dramatic and broad range of effects on metabolism, growth and maturation, sexuality and reproduction, and other important bodily functions.

Conclusion:
As per our discussion on pituitary gland deficiency, we came to know about varied effects of its deficiency on human beings. When the key hormones secreted by this gland become very low in frequency then the level of hypopituitarism is at danger. The death of any person may occur if the thyroid hormone and the adrenal hormone are extremely low. The tumor is also a major risk, which is occurring due to the pituitary gland deficiency

Pituitary Gland

by Rachana Tiwari on Dec 04, 2010

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Pituitary Gland Presentation Transcript