Endocrine System

• Hormone
• -chemical messenger secreted into bloodstream, stimulates response in another tissue or organ
• Target Cells
• -have receptor for hormone
• Endocrine glands
• -produce hormones
• Endocrine system
• -endocrine organs (thyroid, pineal, etc)
• -hormone producing cells in organs (brain, heart and small intestine)

Exocrine Glands:use ducts to secrete their products into body cavities or surfaces

Endocrine Glands: secrete their products into the extracellular space; hormones enter blood and is carried away

• Both systems coordinate the functions of all body systems
• -NS uses action potential conducted along neuronal axons
• -Endocrine system uses hormones that circulate in the blood

• Several chemicals function as both hormones and neurotransmitters
• -NE, cholecystokinin, thyrotropin-releasing hormone, dopamine and ADH
• Some hormones secreted by neuroendocrine cells (neurons)
• -oxytocin and catecholamines

• Both systems w/ overlapping effects on same target cells
• -NE and glucagon hydrolysis in liver
• Systems regulate each other
• -neurons trigger hormone secretion
• -Hormones stimulate or inhibit neurons

• NS and endocrine system are interrelated
• -NS can regulate hormone release
• -Hormones can regulate nerve impulses

• Steroids
• -lipids derived from cholesterol ie sex steroids, corticosteroids

• Peptides and glycoproteins
• -3-200 amino acids made in RER
• -OT, ADH; most of anterior pituitary hormones

• Monoamines (biogenic amines)
• -derived from amino acid tryrosine ie catecholamines (norepinephrine, epinephrine, dopamine, melatonin, and thyroid hormones

• No such thing as a "male" or "female" hormone
• Synthetic pathways are all interrelated

• Synthesized from cholesterol-differs in functional groups attached to 4-ringed steroid backbone 
• Understand cholesterol is modified

• Primary Structure
• -amino acid sequence

• Secondary structure
• -coiled or folded shape
• -hydrogen bonds between negative C=O and positive N-H groups

• Tertiary Structure
• -further folding and bending into globular and fibrous shapes

• Quaternary structures
• -associations of two or more seperate polypeptide chains

• -Parallel, flattened membranous sacs covered in ribosomes
• -Continuous with nuclear envelope and smooth ER
• -Synthesis of packaged proteins (digestive glands) and phospholipids and proteins of plasma membrane

• -Granules of protein and RNA found in nucleoli, free in cytosol and on rough ER
• -Uses directions in messenger RNA to assemble amino acids into proteins specitied by the genetic code (DNA)

• -System of flattened sacs (cisternae)
• -Synthesizes carbohydrates, packages proteins, and glycoproteins
• -Forms vesicles (lysosomes, secretory vesicles, new plasma membrane)

• Transcription
•    -messenger RNA (mRNA) is formed next to an activated gene
•    -mRNA migrates to cytoplasm

• Translation
• -mRNA code is "read' by ribosomal RNA as amino acids are assembled into a protein molecule
• -Transfer RNA delivers the amino acids to the ribosome
• -Translations of mRNA: mRNA begins with leader sequence (binding site for ribosome) start codon AUG

  

• Cellular Steps:
• -RER removes segment, froms prohormone
• -Golgi complex further modifies it into hormone
• -e.g. insulin formation
•   preproinsulin converted to proinsulin in RER
•   proinsulin split into insulin and C peptide in golgi complex

• All are synthesized from tyrosine
• -except melatonin which is synthesized from typtophan

• Thyroid hormone is unusual
• -composed of two tyrosine molecules
• -requires a mineral, iodine

• Follicular Cells
• -absorb I- from blood and store in lumen as I^-
• -synthesize thyroglobulin and store in lumen (contains tyrosine 123)
• -tyrosine and Iodine form T₃ and T₄

• TSH
• -Stimulates follicular cells to remove T₃ and T₄ from thyroglobulin for release into plasma

• Monoamines and peptides are hydrophilic
• -mix easily with blood plasma

• Steroids and thyroid hormone are hyrophobic
• -must bind to transport proteins for transport
• -bound hormone-attached to transport protein
•     prolongs half-life to weeks
•     protects from enzymes and kidney filtration
• -unbound hormone leaves capillary to reach target cell (half life a few minutes

• Transport proteins in blood plasma
• -albumin, thyretin, and TGB (thyroxine binding globulin) bind to thyroid hormone
• -steroid hormones bind to globulins (transcortin)
• -aldosterone -no transport protein, 20 min half life
• hydrophilic hormones flushed out quicker

• -Located on plasma membrane, mitochondria, other organelles, or in nucleus
• -Usually thousands for given hormone
•      hormone binding turns metabolic pathways on or off 
•      molecular switch
• -Exhibit specificity and saturation

Hydrophobic hormones:penetrate plasma membrane-enter nucleus

Hydrophilic hormones: must bind to cell-surface receptors

• Hormone Binding
• DNA Binding
• Transcription activation

*see picture*

-TH binds to receptors on Mitochondria: rate of aerobic respiration

-Ribosome

-Chromatin: Protein synthesis

-Na⁺ K⁺ ATPase produced: generates heat

• 1. Hormone binding activates G protein
• 2. Activates adenylate cyclase
• 3. Produces cAMP
• 4. Activates Kinases
• 5. Activates enzymes
• 6. Metabolic reactions:
• -synthesis
• -secretion
• -change membrane potentials

• Hydrophilic Hormones: Mode of action other 2nd and 3rd Messengers
• *Hormones may use different second messengers in different tissues.*

One hormone receptor interaction>activates many molecules of cAMP>activates many enzymes>greater metabolic effect

• -Hormone signals must be turned of
• -Take up and degraded by liver and kidney
• -excreted in bile and urine
• -Metabolic clearance rate (MCR)
• -Half-life required to clear 50% of hormone

• Long term use of high pharmacological doses
• -bind to receptor sites of related hormones
• -target cell may convert to different hormone
• Ie testosterone----estrogen!

• -Shaped like a flattened funnel, forms floor and walls of third ventricle
• -regulates primitive functions from water balance to sex drive
• -many functions carried out by pituitary gland

• Seperate origins
• -can be thought of as distinct glands that lie in close proximity

• Anterior Pituitary
• -Derived from pharynx
• -Migrates up

• Posterior Pituitary
• -Neuronal in origins
• -Migrates down

• -Suspended from hypothalamus by stalk (infundibulum)
• -Location and size
•  Housed in sella turcica of sphenoid bone
•  1.3 cm diameter

• Adenohypophysis (anterior pituitary)
• -arises from hypophyseal pouch (outgrowth of pharynx)
• Neurohypophysis
• -arises from brain

• Hormones travel in portal system from hypothalamus to anterior pituitary
•   -Capillary network-picks up hormones from hypothalamus for delivery to anterior pituitary
•  -Fenestrated capillaries-more porous than usual

• Hormones secreted by hypothalamus
• -Seven
• -5 promote secretion by anterior pituitary
• -2 inhibit secreation by anterior pituitary

• *See picture*
• Principle hormones and target organs shown
• Axis-refers to way endocrine glands interact

• Tropic hormones target other endocrine glands
• -gonadotopins target gonads
•    FSH (follicle stimulating hormone)
•    LH (luteinizing hormone)
• -TSH (thyroid stimulating hormone)
• -ACTH (adrenocorticotropic hormone)
• -PRL (prolactin)
• -GH (growth hormone)

• OT (oxytocin) and ADH (antidiuretic hormone)
• -produced in hypothalamus
• -transported by hypothalamo-hypophyseal tract to posterior lobe (stores then releases hormones)

Both anterior and posterior are controlled by the brain

• Anterior pituitary
• -Hormones from hypothalamus
• -releasing ro inhibiting secretion

• Posterior Pituitary
• -Neuroendocrine reflexes
•    Hormonal release in response to signals from nervous system
•    Dehydration increases osmolarity of blood osmoreceptors triggers release of ADH to promote water conservation

• Negative feedback
• - increasing target organ hormone levels inhibits release of tropic hormones

• Positive feedback
• -stretching of uterus increases OT release, causes more stretching of uterus, until delivery

The most frequent cause of pituitary disorders is pituitary gland tumors.

The pituitary gland is made of several cell types. Sometimes these cells grow too much or produce small growths. These growths are called pituitary tumors, and they are fairly common in adults.

These are not brain tumors and are not a form of cancer.In fact, cancerous tumors of this sort are extremely rare.

Pituitary tumors, however, can interfere with the normal formation and release of hormones.

• Two types of tumors exist-secretory and non-secretory.
• -Secretory tumors produce too much of a hormone, creating an imbalance of proper hormones in the body.
• - Non-secretory tumors cause problems because of their large size or because they interfere with normal function of the pituitary gland.

Hypersecretion-too much of any hormone secreted into the body is usually caused by a secretory pituitary gland tumor.

• -Many secretory tumors make too much prolactin, the hormone that triggers milk production in new mothers
• -Tumors also can make excess growth hormone or too much of the hormone that stimulates the thyroid gland leading to overproduction of thyroid hormones.
•    Graves disease-autoantibodies attack thyroid and mimic TSH leading to excess TH secretion

Hyposecretion- too little of any hormone secreted into the body is usually caused by a non-secretory pituitary gland tumor, which interferes with the ability of the normal pituitary gland to create hormones.

• -It can, however, also be caused by a large secretory tumor
• -Hyposecretion can also happen with surgery or the radiation of a pituitary gland tumor

Tumor Mass Effects-As a pituitary gland tumor grows and presses against the normal pituitary gland or other areas in the brain, it may cause headaches, vision problems, or other health effects related to hyposcecretion.

-Tumor mass effects can be seen in any type of pituitary tumor that grows large enough. Injuries, certain medications, and other conditions can also affect the pituitary gland. Loss of normal pituitary function also has been reported after major head trauma.

-FSH (secreted by gonadotrope cells) stimulates production of egg or sperm cells

• -LH (secreted by gonadotrope cells) mainly stimulates hormone production
•    In Females stimulates ovulation and corpus luteum to secrete progesterone and estrogen
•    In males stimulates interstitial cells of testes to secrete testosterone

-TSH (secreted by thyrotropes) stimulates growth of gland and secretion of TH

• -ACTH or corticotropin (secreted by corticotropes) regulates response to stress, stimulates adrenal cortex
•    corticosteroids regulate glucose, fat and protein metabolism

• -PRL (secreted by lactotropes)
• -female-milk synthesis after delivery
• -male- increases LH sensitivity, thus increases testoterone secretion

Secreted by somatotropes of anterior pituitary

• Promotes tissue growth
• -mitosis and cellular differentiation
• -stimulates liver to produce IGF-I and II
•    protein synthesis
•      -increases DNA transcription for increased mRNA production, proteins synthesized 
•       -enhances amino acid transport into cells, decreases protein catabolism
•    lipid metabolism
•        -stimulates FFA and glycerol release from adipocytes, protein sparing
•    CHO metabolism
•        -glucose sparing effect=less glucose used for energy
•    Electrolyte balance
•         -promotes Na, K, Cl retention, Ca absorption

• Childhood and adolescence
• -bone, cartilage, and muscle growth
• -stimulates growth at epiphyseal plates

• Adulthood
• -increase osteoblastic activity and appositional growth affecting bone thickening and remodeling
• -blood concentration decrease by age 75 to 1/4 of that of adolescent

• Levels of GH fluctuates throughout the day
• -higher during deep sleep, after high protein meals, after vigorous exercise
• -lower after high CHO meals

• -problems in childhood or adolescence
•    gigantism if over secretion

The child will grow in height as well as in the muscles and organs. This excessive growth makes the child extremely large for his or her age.

• Other symptoms include:
• -delayed puberty
• -double vision or difficulty with side (peripheral) vision
• -Irregular periods (menstruation)
• -Large hands and feet with thick fingers and toes
• -Release of breast milk
• -Thickening of the facial features
• -Weakness

• In pituitary tumors with well-defined borders
• -surgery is the treatment of choice and can cure many cases.

• For situations win which surgery cannot completely remove the tumor:
• -medication is the treatment of choice
• -the most effective medications are somatostatin analogs which reduce growth hormone release
• -dopamine agonists have also been used to reduce growth hormone release, buth there are generally less effective.
• -Radiation therapy has also been used to bring growth hormone levels to normal.
• -However, it can take 5-10 years for the full effects to be seen and this almost always leads to low levels of other pituitary hormones

• Dwarfism
• Children with growth hormone deficiency have a slow or flat rate of growth, usually less than 2 inches per year.
• -The child will be much shorter than most or all children of the same age and gender
• -children with growth hormone deficiency still have normal body proportions as well as normal intelligence. However, their face often appears younger than children of the same age. They may also have a chubby body build.
• -GH can be produced in E. Coli and used to treat pituitary dwarfism

Hypersecretion of growth hormones