Download Endocrine Physiology - system of glands that synthesize and secret

Endocrine Physiology
- system of glands that synthesize and secret hormones directly into vascular system without any ducts
Hormones
- help to regulate and control metabolic processes
- control rates of reaction
- transport of substances
- water an electrolyte balance
- growth and development
- sex and reproductive activity
Hormones are incredibly POWERFUL biological agents
- a few nanograms could have a BIG EFFECT on any one of those previous functions
Classified as being either:
- steroid based
- synthesize from a backbone of cholesterol
- non steroid
- several categories:
- amines
- peptides
- proteins
- glycoproteins
- synthesized from amino acids
Steroid Hormones
- sex hormones
- estrogens and androgens
- aldosterone and cortisol (from adrenal cortex)
Vitamin D – a modified steroid that is converted into dihydroxycholcalciferol
Dihydroxycholcalciferol - hormone that promote the absorption of calcium and phosphorous from the intestines
Non Steroid Hormones
Amines
- synthesize from the amino acid tyrosine
- S & S from the adrenal medulla
- also know as catecholamines (NE and E)
Peptide
- short chain amino acid hormones
- include two hormones that are secreted from the neurohypophysis (posterior pituitary)
- oxytocin
- ADH
- some of the hypothalamic releasing factors
- TRH (thyrotropin releasing hormone)
- GNRH (gonadotropin releasing hormone)
- GIH (growth inhibiting hormone)
Proteins
- longer chain amino acids
Include:
- parathormone
- GH (growth hormone)
- prolactin
Glycoproteins
Gonadotropins
- FSH
- LH
Stimulating Hormone
- TSH
Hormones that affect the metabolism of target cells are usually derived from less active or parent (precursor)
molecules
Ex: The islets of Langerhan (insulin) or the cells of the anterior pituitary (ACTH) – synthesize and secrete insulin or
ACTH – these hormones are derived from LARGER, LESS ACTIVE polypeptides within the endocrine cells of the
gland
- larger, less active cells - Prohormones
- these prohormones are NOT secreted into the vascular system
The concentration of these prohormones is VERY LOW in vascular system of an individual
- should not be there
Tetra Iodothyronine (T4) and Testosterone
- converted to their more active molecules IN THE TARGET CELLS where they will be utilized
- secreted in their prohormone form (inactive)
- would expect to see their prohormone form in the vascular system
- released in INACTIVE FORM  ACTIVE FORM (in target cells)
Prehormone
- hormones like T4 and testosterone
- are released in their inactive form
- not activated till they get to their target tissue
- expect to see in the vascular system
The concentration of a hormone or prehormone in the blood
- reflects the rate of secretion by the gland
Hormones DO NOT accumulate in the vascular system
Half life of Hormones
- 2 mins to 2 Hrs
Hormones are readily removed from the blood by target tissues and liver
Effect of Hormones
- HIGHLY concentration dependent
Normal Response – requires a certain physiological concentration of that hormone in the vascular system
Abnormally High Concentrations  Non Characteristic Effects in the Body
Abnormally High Concentration of Certain Hormones  cause hormone to bind to tissue receptor that is similar
to the receptor it normally binds to
Steroid hormones can be converted to other biologically active chemicals by their target cells
(Ex: some cells can convert androgens into estrogens)
1- Administration of large amounts of steroid compounds  result in a significant amount of other steroids
2- Target tissue does not respond to other hormone that is being secreted
- if your body is telling your adrenal cortex to increase S&S of androgen, and if that place is not utilizing it, then you
will have too much androgen
 then androgens would be converted to estrogens and would produce a noncharacteristic response
Desensitization and Down Regulation
Prolonged exposure to polypeptide hormones (ADH, oxytocin, ARH) in high concentrations can desensitize target
cells to those hormones
 the same concentration of the same hormones produces less of a response
This desensitization may be due to a decrease in the number of receptor proteins in the target cells (Down
Regulation)
- number of receptors proteins on target tissue decreases
- takes place in:
- adipose tissue - in response to insulin
- testicular cells - in response to LH
Hormone Interactions
The response of a target tissue to a hormone
- NOT ONLY due to the concentration of a hormone, but also to the action of other hormones on the same tissue
Hormones can modify the affect of target cells by:
1- Changing the number of receptor sites available
2- Altering the activity of enzymes needed to activate other hormones
3- Altering the activity of target cells enzymes that deactivate other hormones
Some hormones have a PERMISSIVE EFFECT
- enhances the response of a target tissue to another hormone
- increase the activity of another hormone
Ex: Estrogen(during 1st half of 28 day cycle) promotes the formation of progesterone receptor sites in the uterus
- When progesterone is synthesize and secreted (2nd half of cycle)  its effect is more immediate and
enhanced
Ex: Exposure of the gonads (ovaries or testes) to FSH stimulate the production of LH receptor sites
 enhances the response of testes or ovaries to LH
Hormones also have SYNERGISTIC PROPERTIES
- their effects are complimentary
- the sum of their actions cannot be accomplished by any one hormone
Ex: Sperm production requires the synergistic actions of FSH and the androgens
Ex: Mammary gland production and secretion of milk requires the synergistic actions of estrogen, cortisol, prolactin,
oxytocin
Some hormones have ANTAGONISTIC EFFECTS
Ex: insulin and glucagon – insulin lowers blood glucose and glucagons raises blood glucose
another ex: during pregnancy, estrogen prevents secretion af actin and prolactin
Mechanism of Action
Hormones are carried to every cell in the body by the vascular system
****However, due to the specificity of receptor proteins on target cells, hormones ONLY act on specific tissue
Based on location of the receptor proteins, hormones are grouped into three categories:
1- Within the nucleus of the target tissue
Ex: Thyroxin – within the nucleus of target tissue
2- Within the cytoplasm of target cells
Ex: Androgens and Estrogens (steroid hormones)
3- On the outer surface of the target cell membrane
Ex: Catecholamines (NE and E)
Hormones in Nucleus or in Cytoplasm (Categories 1 and 2)
- similar in both:
- hormones NOT water soluble
- therefore, they are transported by carrier proteins to their target tissue.
Mechanism of Action
1- Transported by carrier proteins to their target tissue
2- Once in their target tissue, they dissociate from their carrier proteins
3- Pass through the lipid component of the cell membrane
4- The hormone attaches to a cytoplasmic receptor protein
5- Receptor protein with the hormone translocates to the nucleus
6- Then attaches by means of another receptor protein complex to the chromatin on the DNA
- site of attachment on chromatin – acceptor site these are what are specific for
tissues.
7- The attachment on the DNA ACTIVATES specific genes on the DNA
8- Those genes produce nuclear RNA
9- RNA is processed into messenger RNA
10- Messenger RNA leaves the nucleus and enters the cytoplasm
11- Attaches itself to ribosomes  resulting in synthesis of new proteins
Hormone itself is NOT causing the action or change in activity
Those proteins being synthesized may be:
- enzymes - produced by ribosomes
Steroid hormones – could result in protein synthesis
It is the proteins that are mediating the effect – NOT the hormone itself
Thyroxine (Where the receptor is in the nucleus)
Thyroid gland:
- Secretes T4
- T4 travels bound to a carrier protein
- the carrier protein that transports T4 is TBG (Thyroxine Binding Globulin)
- Secretes a small amount of T3
- TBG has a MUCH HIGHER affinity for T4 than is does for T3
 normally the plasma concentration of FREE T3 is 10x HIGHER than
T4
target
- ONLY FREE T4 can enter target cells
- 99% is bound by TBG, and 1% is FREE – which enter target cells
- the rest is a reservoir (T4 bound by TBG) – which makes it different from other
hormones
- That is why it takes several weeks after the removal of a thyroid gland for symptoms of Hypothryoidism to occur
- once free T4 passes into the target cell, it’s converted to T3 by enzymes with in the cytoplasm. There are inactive
T3 receptor proteins in the nucleus and when T3 enters the nucleus from the cytoplasm, those receptor proteins are
activated and from that point the sequence is the same as it is with steroid.
Mechanism of Action
1- Transported by carrier proteins to their target tissue
2- Once in their target tissue, they dissociate from their carrier proteins
3- Pass through the lipid component of the cell membrane
4- The hormone attaches to a cytoplasmic receptor protein
5- Receptor protein with the hormone translocates to the nucleus
6- Then attaches by means of another receptor protein complex to the chromatin on the DNA
- site of attachment on chromatin – acceptor site these are what are specific for
target
tissues.
7- The attachment on the DNA ACTIVATES specific genes on the DNA
8- Those genes produce nuclear RNA
9- RNA is processed into messenger RNA
10- Messenger RNA leaves the nucleus and enters the cytoplasm
11- Attaches itself to ribosomes  resulting in synthesis of new proteins
Mechanism of Non Steroid Hormones (on outer surface) (Category 3)
-amines, polypeptides, glycoproteins
- cannot pass through the lipid barrier of the target cell (not that soluble)
- some may pass through membrane by pinocytosis
- MOST of the non steroid hormones exert their effects from the interaction on the hormone with receptor proteins
on the cell membrane outside the cell
- since these hormones DO NOT have to enter the cell in order to exert their effects, other molecules
mediate their actions inside the cell
- the hormones themselves are referred to as messengers from the endocrine gland to the target cell
- the molecules within the cell that mediate their effects are referred to as the second messengers
Cyclic AMP (cAMP)
- first 2nd messenger to be discovered
- best understood
The Effects of…:
- ACTH
- Calcitonin
- Catecholamines (NE and E)
-FSH/LSH
- TSH
-ADH
- Glucagon
… ARE ALL mediated with cAMP as a 2nd messenger
In addition, the effects of NE as a neurotransmitter involves cAMP synthesis
The binding of these hormones, requiring cAMP, to the cell membrane receptor ACTIVATES adenyl cyclase
Adenlyl Cyclase
- located within the cell membrane
- causes the breakdown of ATP within the cytoplasm into cAMP and some inorganic
 cytoplasmic concentration of cAMP is INCREASING
phosphate
Protein Kinase
-has two subunits. Inhibitory and catalytic sub units
cAMP ACTIVATES the INACTIVE (inhibitory) protein kinase
- Active (catalytic) protein kinase mediate hormone’s action
cAMP must be deactivated in order to control the hormone
DEACTIVATED by: phosphodiesterase
Binding of Hormone to Cell Membrane Receptor  Adenyl Cyclase Activated  cAMP Concentration Increases
 Protein Kinase Activated  Mediate Action of Hormone
Phosphodiesterase  Deactivates cAMP
Thiopthylline – inhibits phosphodiesterase
- prevents the breakdown of cAMP in bronchiolar smooth muscle
- prevents the muscle from contracting
- keeps muscle in state of bronchodilation
Ionic calcium functions as a second messenger with some hormones, as cal modulin.
Control of hormone secretion in almost all cases is a negative feedback mechanism
Glands
-Adrenal Madulla and pituitary secrete in response to neural stimuli
Pituitary Gland (Hypophysis)
- connected to they hypothalamus with a thin piece of tissue, Infundibulum
-with in the infundibulum with the portal system, hypothalamic hypophysial portal
system.
-Physiologically pituitary is divided into anterior and posterior but anatomically it is very hard to tell the two parts to
distinguish between them
-Anterior portion, embriologically, developes from epithelial tissue and it’s cells are
epithiloid in
nature
-while the posterior pituitary developes from the hypothalamus and it’s cells are glial
nervous system
like cells
-basically 6 key hormones that are synthesized AND secreted from the anterior pituitary (adohypophysis)
1- Growth Hormone
- affecting the growth of the body – by enhancing protein synthesis
2- ACTH
- exerts its affect on the adreno cortex
- involved metabolism of carbohydrates, proteins, and fats
3- TSH
- affects thyroid gland activity
4- Prolactin
- associated with mammary gland development and milk production
Gonadotropins
– growth of gonads and reproductive function
5- FSH
6- LH
Posterior Pituitary
Two hormones that are secreted in but not sythesised in:
1- ADH (antidiuretic hormone) [Vasopressin]
- controls rate of water reabsorption in the nephron
2- Oxytoxin
- associated with milk let down during lactation
- has a role in parturition
Anterior Pituitary
- has a special cell type associated with each of the major hormones with the exception of FSH and LH, they come
from the same cell type
Somatotrophs
- cells associated with S&S of growth hormones
- These stain very well with acid stains, and so are referred to as acidophilic or acidophils.
- Pituitary tumors secreting large amounts of growth hormone are called acidophilic tumors because of the
way they absorb acidic dyes
Corticotorphs
- associated with synthesis of ACTH
Thytotophs
- associated with TSH
Lactotrophs
- associated with prolactin
Gonadotrophs
- associated with FSH and LH
Control of the Secretion of Hypophyseal Hormones
With regard to the anterior pituitary hormones:
- controlled by hypothalamic releasing hormones
Control of Release of Posterior Pituitary Hormones
- by nerve fibers from the hypothalamus
Hypothalmic Hypophyseal Portal System
- located directly between the hypothalamus and pituitary gland
- intricate network of blood vessels
Special neurons in the hypothalamus S&S hypothalamic releasing AND inhibiting factors (factor = hormone [ in
hypothalamus]) that control secretion of the anterior pituitary
Major Releasing Factors
- TRF (thyroid releasing factor)
- causes release of TSH from anterior pituitary
- CRH (corticotropic releasing hormone)
- causes ACTH release
- GH
- releasing and inhibiting factor (aka. somatostatin-affect the release of growth hormone)
- causes hormone release or suppression
- LRH (gonadotropin releasing hormone)
- triggers FSH and LH release from the anterior pituitary
- Prolactin Inhibiting Factor
- inhibits prolactin release
Growth Hormone
- ONLY hormone of the anterior pituitary that exerts its effect on almost EVERY CELL in the body as opposed to
specific target tissue
- causes hypertrophy and hyperplasia of all cells in the body capable of growing
GH also has some metabolic effects aside from growth affects:
Effects on protein:
- increase in rate of protein synthesis on all cells in the body by promoting amino acid transport into the
cells, believed by working directly on the ribosomes
- reduces protein catabolism (breakdown)
Effects on fats:
- causes the release of fatty acids from adipose tissue
 increasing fatty acid concentration in the body fluids
- enhances the conversion of fatty acids into acetyl CoA
- a doorway into aerobic metabolism, increasing fat metabolism for energy
- promotes fat metabolism by the cells over carbohydrate metabolism
- occasionally, fat mobilization is so great that excessive quantities of acetyl CoA formed by the liver and are
released causing ketosis
Effect on carbohydrates:
- decreases the use of glucose by the cells
- enhances glycogen deposition (mainly in muscle tissue)
-increases blood glucose uptake by the cells therefor increasing blood glucose
concentration.
-Insulin is essential for growth hormones to be effective
Growth Hormone has a Diabetogenic Effect on the body
- mimicking diabetes
Regulation of GH secretion
Normal in adults is about 3g/mm and in children about 5g/mm
IT’s basic control is based on releasing and inhibiting factors Via:
- growth hormone releasing factor (GHRH) from the hypotalamus
- growth hormone inhibiting factor (GHIH) from the hypothalamus, aka somatatropin
- S&S by the delta cells in the islets of langerhan in the pancreas
Growth hormone is released throughout life, with an increase based on your state of nutrition or stress.
Posterior Pituitary
Two hormones that are:
- synthesized in the hypothalamus and secreted from the posterior pituitary
- They are almost structurally the same
1- ADH
-increases the permeablility of the collecting ducts in the kidney, increasing the reabsorption of water.
With out ADH, there is a dramatic increase in urine volume and
dramatic decrease in urin concentration.
-it’s control is based on the osmotic pressure in the plasma by ossmo receptors in the
hypothalamus
-effects of ADH really controls extracellular sodium concentration more than water
concentration.
- Increase in ADH assoc with pain and anxiety
- pathology assoc is diabetes insipidus, receptors in hypothalamus are diseased or
destroyed
- synthesized in supraoptic nucleus of the hypothalamus
2- Oxytoxin
-assoc with uterin contractions, use pitosin to induce labor
-also plays a role in lactation because it causes milk to be expressed from the alveoli
in the breast
- synthesized in the paraventricular nucleus of the hypothalamus
Thyroid
-located below larynx and anterior to trachea
Blood Flow to Thyroid
- has superior off the external carotid and inferior thyroid artery off the subclavian respectively
Three Hormones (all S&S)
1- T4
2- T3
3- Calcitonin
-important to these hormones is elemental iodine. To make sure we get enough iodine, common table salt is iodized.
-thyroid gland is composed of closed follicles which thyroglobulin is secreted into the follicle where T3 and T4 bind
to the thyroglobulin
Thyroid Hormone T3 and T4
- associated with increasing your metabolic rate
Without a thyroid and without replacement of thyroid hormone,
 your basil metabolic rate(BMR) DECREASES by 40%
With excess thyroid secretion,
 BMR INCREASES to 60-100% greater than normal
T3/T4
- INCREASES protein synthesis by the ribosomes of cells
- Increase enzymatic activity assoc with ribosomal synthesis
- INCREASES the rate of carbohydrate metabolism
 by INCREASING the activity of all of the enzymes associates with aerobic metabolism (ie. Krebs
cycle)
- cause hypertrophy and hyperplasia of mitochondria (site of aerobic metabolism)
- extremely excessive T3/T4 (hyperthyroidism) oxidative phosphorylation is uncoupled by the mitochondria
produce an enormous amount of heat lost instead of joining to form ATP
- People with overactive thyroids  thin and always warm
- reverse is true with hypothyroidism
- INCREASES the activity of sodium/potassium pump
- they are needed for growth, brain development and fetal life
- problem in new borns, then these hormones must be administered with in days post partum or there will
be mental deficiencies.
Regulation
Via:
- TSH from the anterior pituitary
TSH
- INCREASES the proteolysis of thyroglobulin (TBG) releasing of T3 and T4
- allows T3 and T4 to be dissociated from its transport
- INCREASES the rate of iodine trapping by the thyroid gland
 providing for the synthesis of T4
- causes hyperplasia of thyroid cells
Adrenal Cortex
Three vessels through Adrenal Gland:
1- Suprarenal Artery off the inferior phrenic
2- Middle Suprarenal Artery off the abdominal aorta
3- Inferior Suprarenal Artery off the renal artery
Each gland contains:
- Medulla
- S&S catecholamine
- action is associated with sympathetic division of ANS
- Cortex
Divided into three sections:
1- Zona Glomerulosa
- S&S aldosterone
2- Middle Zona Fossiculata
- S&S glucocorticoids
3- Inner Zona Reticularis
- S&S androgens
Mineralocorticoids
over 30 hormones from the cortex
Aldosterone
- secreted from Zona Glomerulosa
- total loss of adrenal cortico secretions result in death in a few weeks with out therapy
- With out ECS rises dramatically and Cl and Na decrease dramatically and equally a decrease in blood volume
- MAJOR EFFECT on extracellular fluid concentration of sodium and potassium ions
- sodium concentration rises, potassium concentration falls
- causes an INCREASE in sodium ion reabsorption at the expense of potassium secretion in the nephrons of the
kidney. This increases osmotic pressure in peritubules surrounding the nephron leading to an increase in water
reabsorption
- Aldosterone has a much higher effect on ECF concentration that sodium concentration. Excess aldosterone
increase ECF greater than 10-20%
 tends to raise blood pressure (BP)
Downside:
- could make you hypokalemic (as low as 1-2ml/L- normal is about 3-4)
- potassium at 1/2 it’s normal causes muscle weakness d/t properties of nerve and muscle fiber membranes
-hyperkalemia could reach 2 times normal and these levels assoc. with cardiac toxicity, decrease in myocardial
conctractility and arrhythmia
Regulation
-zona glomuerulosa works independently from the others
- linked directly to extracellular sodium concentration
- linked to Renin Angiotensin System
INCREASE levels of angiotensin 2  INCREASE in aldosterone secretions
-Effects of sodium ion concentration: a decrease leads to a decrease in ECF volume which then creates a cascade
leading to decrease in CO leading to a decrease in renal blood flow triggers secretion of Renin leading to renin
angiotensin activation
Glucocorticoids (ACTH affects here not mineralocorticosteroids)
-s&s in middle layer
Cortisol
- stimulates gluconeogenesis (synthesis of glucose from NON carbohydrate substrates)
- DECREASES glucose utilization by the cells
- ELEVATES blood glucose levels
- making more, but not letting cells use it
On proteins:
- REDUCES protein stores in all body cells accept the liver
- by decreasing amino acid transport into the cells of the body
On fats:
- mobilizes fats and fatty acids from adipose tissue
- with their subsequent use for energy
- Cortisol is released when your body is under any form of stress
Any stress  increase ACTH which causes an increase in cortisol levels
-have anti-inflammatory effects
5 Inflammation processes:
Occurs:
1- When there is a release of inflammatory chemicals, such as histamine
2- When there is an increase in blood flow to the area of insult (where injury is)
3- When there is plasma leakage into the area of damaged tissues
4- When there is infiltration by leukocytes into the region
5-release of inflammatory mediators
Cortisol
- DECREASE capillary permeability
- less plasma leakage
- less leukocyte infiltration
- DECREASE the release of the inflammatory substances (histamine)
-suppressed T cell activity, which reduces tissue activity and inflammation
-REDUCES vasodilation
Cortisol is an EXCELLENT ANTI-INFLAMMATORY
Cortisol is under the control of ACTH (anti pituitary hormone)
- ACTH is regulated by CRF from the hypothalamus
Pancreas
- in addition to the digestive juices that is produces,
Contain:
- endocrine cells – called Islet of Langerhan
- Islets of Langerhan contain:
- alpha cells – synthesis and secrete glucagon
- beta cells – synthesize and secrete insulin
- delta cells – synthesize and secret somatostatin
Insulin
- released when blood glucose levels are elevated, most problems assoc with fat metabolism
- causes a DECREASE in circulating levels of blood glucose
- Does this in several ways:
-by facilitating glucose transport into the cells of your body
- after we eat, blood sugar rises and glucose stored for later. Insulin causes glucose uptake and storage by the liver
Insulin increases liver glycogen in the following ways:
1- INHIBITS the enzyme phophorylase (enzyme that causes liver glycogen to split into glucose)
2- ENHANCES the activity of glucokinase (enzyme that phosphorylates glucose when it is in the liver  trapping
glucose in the liver b/c once it’s phosphorylated it can’t leave)
3- INCREASES the activity of phosphofructokinase and of glycogensynthetase
- both of these enzymes cause a 2nd phophorylation of glucose
 converting it into glycogen causing all actions to be reversed and
raising glucose in the blood
-Insulin facilitates glucose transport through the muscle membranes
Fat metabolism:
-It acts as a fat sparer. When there as a lack in insulin there is an increase in fat metabolism (ex of atkins diet)
Protein metabolism:
-insulin causes active transport of AA into cells (valiene, lieucine, tyrosene, phenyalanine)
-in the liver, insulin inhibits catabolism of protein allowing us to use it for tissue growth
Glucagon
- has the exact OPPOSITE effect
- INCREASE blood glucose
- BEST UNDERSTOOD cyclic AMP cascade
- released when blood glucose concentrations fall  INCREASE in blood glucose levels
Parathyroid Gland
behind inferior and superior lobes of thyroid
Synthesizes and secretes:
- Parathormone (PTH)
-causes an increase in calcium in the plasma via two ways:
1- causes osteolysis (breakdown of bone cells around the layer of bone releasing stored
calcium
and phosphorous)
- this breakdown occurs in a superficial layer just below the periosteum where
most of
the cells are NOT in the ossified state (in liquid format)
2- ACTIVATES osteoclasts (cells that facilitate the release of calcium and phosphorous from bone tissue)
- needed for conversion of hydroxycholcalciferol into dihydroxycholcalciferol
Dihydroxycholcalciferol
- essential for calcium absorption in the GI tract
Control of Parathormone Release
- based on ECF calcium concentration
If ECF calcium concentration falls, parathormone secretion INCREASES
Calcitonin
-s&s by the parafolicular cells of parathyroid
-anatagonistic of parathormone
- does the exact OPPOSITE of parathromone
-If ECF calcium concentration is high, calcitonin facilitates the storage of calcium by the skeletal system
and decreases the calcium concentrations in the plasma by decreasing osteoclast activity and by increasing
osteoblastic activity