Endocrine System – outline notes

I. Endocrine Axis
Endocrine Gland — Hormone — Blood — Target tissue — Effect

II. Hormones – chemical messengers
A. 3 classes
1. Amino acid derivatives
-catecholamines – from tyrosine
-epinephrine and norepinephrine
-thyroid hormones – from tyrosine
-melatonin – tryptophan


2. Peptide Hormones – chains of amino acids
-pituitary, hypothalamus, heart, thymus, GI tract, pancreas
*some anterior pituitary are glycoproteins (TSH, LH, FSH)
-also EPO and Inhibin
3. Lipid derivatives
–Steroids – from cholesterol
-sex hormones, adrenal cortex hormones, kidneys(calcitriol)
-Eicosanoids – from arachidonic acid
-paracrine factors – local effect on tissues
-ex) prostaglandins

B. Target tissues have specific receptors that bind hormones
C. After hormone binds receptor – cellular operations are altered
1. Alter protein synthesis
2. Alter existing protein

III. Receptors – two types
A.  Membrane receptors
B. Intracellular receptors

IV. Membrane receptors – on surface of cell membrane
-peptide hormones and catecholamines
-not lipid soluble
-can not diffuse across lipid bilayer
-bind to membrane receptors

 

-Need to produce Second Messenger 
ex) cAMP
-Hormone–receptor complex — activates G-protein —activates
adenylate cyclase —- converts ATP to cAMP —cAMP activates kinases which activate important cellular enzymes by phosphorylation —-EFFECTS CELL BEHAVIOR

V. Intracellular receptors
-Steroid hormones / thyroid hormone
-lipid soluble
-can diffuse across lipid bilayer
-bind to receptors in cytoplasm or nucleus
-steroid-receptor complex binds to DNA — hormone responsive elements
(HRE’s)
-activates or inactivates genes; alters rate of transcription
(protein synthesis)
ex) Testosterone increases protein synthesis in skeletal muscle

VI. Endocrine gland stimuli

1. Humoral – gland responds to changing levels of ions or nutrients
ex) glucose levels on pancreas

2. Neural – nerve fibers stimulate hormone release
ex) SNS stimulates adrenal medullae — catecholamines

3. Hormonal – hormone stimulates glands to release another hormone
ex) hypothalamus and anterior pituitary relationship

 

Major Endocrine Organs

VII. Pituitary (hypophysis)
-sella turcica in sphenoid bone
-hangs from the hypothalamus by infundibulum (stalk)
-Two parts
-Adenohypophysis (anterior pituitary)
-Neurohypophysis (posterior pituitary)

A. Anterior Pituitary
-connection with the hypothalamus
-hypophyseal portal system
–Vascular
   -blood vessels linking two capillary beds (one at a median
eminence in the hypothalamus and one at the anterior pituitary)
-hypothalamus controls ant. pit. hormone production and release
-Releasing hormones (RH) and Inhibiting hormones (IH)
-regulated by Negative Feedback

Endocrine Axis   
Example

-Hypothalamic-Testicular Axis
-hypothalamus
|
|  Releasing hormone (GnRH)
|
-hypophyseal portal system
|
|
-anterior pituitary
|
|
-synthesis and release of ant. pit.     hormones into blood
   | (Luteinizing H)
|
-target tissue (Testes)
|
|
-release of hormone (Testosterone)

Hormones of the Adenohypophysis

Ant. pit. H Hypothalamic- Releasing Hormone Target Tissue Effects

Thyroid Stimulating H. (TSH) Thyrotropin-releasing H. (TRH) Thyroid Gland Release of Thyroid H.
Adrenocorticotropic H. (ACTH) Corticotropin-releasing H. (CRH) Adrenal Cortex Release of glucocorticoids
Follicle Stimulating H. (FSH) Gonadotropin-releasing H. Testes/Ovaries Sperm development/Ovarian follicle maturation
Luteinizing H. (LH) or (ICSH) Gonadotropin-releasing H. Testes/Ovaries Testosterone production/E2 and P4, ovulation
Prolactin (PRL) Prolactin-releasing factor (PRF) and Prolactin-inhibiting factor (PIH, Dopamine) Mammary glands Increase secretory tissue in breast, promote lactation
Growth H. (GH) or Somatotropin GHRH (somatocrinin)
Growth Hormone –
-released episodically at 2-hour intervals
-release stimulated by sleep, arginine, protein meal, exercise, stress
– 2 mechanisms of action
1) Indirect – GH causes the liver to release somatomedins  or IGF’s
-IGFs stimulate skeletal muscle, cartilage, and other cells to uptake
amino acids and increases protein synthesis
-IGF’s stimulate GHIH and inhibit GHRH
2) Direct –
-stimulates epithelial and CT stem cell division
-stimulate lipolysis in adipocytes;  many tissues in the body then
stop using glucose and start using circulating fatty acids
** Glucose Sparing Effect
-this causes blood glucose to rise ** Diabetogenic Effect

 

B. Posterior Pituitary
-connection with the hypothalamus
-hypothalamic-hypophyseal tract
-neural (axons)
-The hypothalamus produces 2 hormones; they are sent to the posterior pit. by
hypothalamic-hypophyseal tract
-post. pit. stores and releases hormones

Two Hormones
1.  Antidiuretic Hormone (ADH or vasopressin)
-released stimulated by a drop in BP, BV, increased blood osmolarity,
angiotensin II
-Function – conserve water at the kidneys, vasoconstriction

2.  Oxytocin (OT)
 -promotes labor contractions
-“milk let-down” – milk ejection

VIII. Thyroid gland – anterior neck
Thyroid Hormones
-thyroid follicles –surrounded by follicular cells(simple cuboidal epithelium)
-colloid – proteins and thyroglobulin(contains tyrosine)
-Steps of thyroid hormone synthesis
1. Iodide ions enter follicular cells under TSH
2. Iodide ions attach to the tyrosine of thyroglobulin
3. Thyroid hormones are formed with thyroglobulin and released
under TSH

-Two hormones
-Thyroxine – T4
-90% released in this form, but converted to T3 in tissues
-Triiodothyronine – T3
-the most active form

-Action
-T3 binds to cytoplasmic, nuclear, and mitochondrion receptors
-increases metabolism, increases ATP production

Calcitonin
-parafollicular cells – between follicles
-Released when calcium levels are high
-Lowers blood Calcium levels
-inhibits osteoclasts
-enhances kidney excretion of calcium
IX. Parathyroid Glands
-2 pairs in the posterior thyroid gland
-Parathyroid Hormone – released when calcium levels are low
-Elevates blood Calcium levels
-stimulates osteoclasts
-inhibits osteoblasts
-inhibits kidney excretion of calcium
-enhances secretion of calcitriol in the kidney (Ca2+ absorption at GI)

X. Thymus
-posterior to sternum (mediastinum)
-maximum size at puberty, then atrophies and becomes fibrous (involution)
-Thymosin
-immune function;  T-lymphocytes

XI. Adrenal Glands
A. Pyramid shaped with fibrous attachment to the superior border of each kidney
B. Two parts
1. Adrenal cortex – outer region
2. Adrenal medulla – inner region
C. Adrenal Cortex
1. Produces steroids (corticosteroids)
2. Divided into 3 zones
a. Zona glomerulosa – outermost layer
b. Zona fasciculata – middle layer
c. Zona Retcularis – the deepest layer
3. Zona glomerulosa
a. Mineralocorticoid production
b. Aldosterone – major mineralocorticoid
1) Function
a) Conserve Na+ / eliminate K+
2) Release stimulated by
a) High K+, renin-angiotensin mechanism, low Na+
3) Renin-angiotensin mechanism
a) Low blood pressure/volume stimulates kidneys to
release renin
b) Renin converts angiotensinogen (plasma protein)       to angiotensin I
c) Angiotensin-converting enzyme (ACE) modifies
angiotensin I to angiotensin II
d) Angiotensin II
1) Release of aldosterone
2) Release of ADH
3) Stimulate thirst
4) Vasoconstriction
4. Zona fasciculata
a. Glucocorticoid production
b. Cortisol – major glucocorticoid
1) Function
a) Increase blood glucose, amino acids, and fatty      acids
b) Anti-inflammatory effects
2) Release stimulated by
a) Adrenocorticotropic hormone (ACTH)
3) Any stress/trauma results in the release of corticotropin-releasing hormone (CRH) from the hypothalamus which      stimulates the release of ACTH from the anterior pituitary
5. Zona reticularis
a. Produces small amounts of androgens

D. Adrenal Medulla
1. Produces epinephrine and norepinephrine
2. Enhance the sympathetic nervous system (SNS) / “fight-flight”
a. Increased heart rate, general vasoconstriction, increased BP
b. Increase metabolism, increase blood glucose

Thinking about the Adrenal Glands:
1.  Why is the adrenal cortex essential for life and not the adrenal medulla?
2. Why is an overactive hypothalamic-adrenal axis often associated with immune compromise, increased susceptibility to disease, and overall health risk?  In other words, why can severe, chronic stress be extremely damaging to your body?  Although stress cannot be completely eliminated from our lives, what sort of things can you do to help decrease it?
3. What would you expect to see with cortisol and ACTH levels in a stressed-out animal?
4. With an adrenalectomy, what would you expect to find with levels of cortisol and ACTH?  Why?
5.  How does a stressful situation increase your blood pressure?
6. Why are ACE-inhibiting drugs used to control blood pressure?
7. What is the purpose of cortisol’s function in increasing blood glucose levels?
8. What would you expect a complete lesion to the hypophyseal portal system would do to cortisol levels?  Why?
9. Why would you expect to find high levels of stored cholesterol in the adrenal cortex?
10. Why would a severe laceration to your leg result in the release of renin, aldosterone, epinephrine, ADH, and cortisol?  What role would each of these play? Why might you also feel thirsty?

XII. Pancreas
A. Wraps posteriorly around the stomach
B. Exocrine pancreas – release substance into the duct
1. 99% of the volume
2. Pancreatic acini – clusters of gland cells
3. Produce digestive juices
C. Endocrine pancreas – release hormones into the blood
1. Islets of Langerhans – balls of hormone-producing cells
a. Alpha cells
1) Release glucagon when glucose levels drop
2) Glucagon targets liver
a) Glycogenolysis
b) Gluconeogenesis
c) Release of glucose into the blood
3) Elevates blood glucose
4) Glucagon is a hyperglycemic (increases glucose in the blood)     agent
b. Beta cells
1) Release insulin when glucose levels (70-110mg/dl) are      elevated
2) Effects of insulin
a) Allows glucose to enter target cells — this lowers
blood glucose levels (hypoglycemic effect)
** Most cells are insulin dependent; brain and
kidney cells are examples of cells that do not need insulin for glucose uptake
b)  Stimulates glycogen and triglyceride formation in liver
and fat cells, respectively

Thinking about the Pancreas
1. Based on the chemical structure of insulin, would you expect it to target membrane or intracellular receptors?
2. Would you expect glucagon to use a second messenger system?
3. What would you expect to see if a person’s pancreatic beta cells were destroyed?  What disease would this result in?
4. If insulin receptors were not functioning properly, what would you expect to see?
5.  See the diabetes mellitus handout

XIII. Pineal Gland
A. Posterior roof of III ventricle
B. Pinealocytes – produce melatonin
C. Melatonin production is affected by light
1) Lowest during the daylight, highest at night
D. Functions of melatonin
1) Sexual maturation
a. Pineal gland tumors that eliminate melatonin production cause
premature puberty
2) Circadian rhythms – day-night cycles

Thinking about the Pineal Gland
1. Seasonal affective disorder (SAD) has been associated with high melatonin levels.  Would you expect this disorder to be more frequently seen in individuals who get a lot of sunlight or very little sunlight?  Why might intensive light exposure be a treatment for this disorder?
2. Would you expect melatonin levels to be relatively high or low around puberty?

XIV. Kidneys
A. Calcitriol
1. Steroid hormone released by the presence of parathyroid hormone
2. Stimulates calcium and phosphate ion absorption in intestines
3. Review cholecalciferol to calcitriol pathway
B. Erythropoietin (EPO)
1. Released in response to low oxygen levels
2. Stimulates the production of red blood cells
3. Increased number of RBCs allows for greater oxygen-carrying
C. Renin
1. Enzyme released in response to decreased blood flow/pressure to kidney or
sympathetic nervous system stimulation
2. Review Renin-Angiotensin-Aldosterone Mechanism

Thinking about the Kidney in a role other than in urine formation
1. How do you expect calcitriol would affect parathyroid hormone secretion?  What kind of regulation would this be?
2. How would low calcium levels affect calcitriol secretion?
3. How could lack of dietary vitamin D and lack of sunlight lead to bone disorders?
4. Why might an athlete inject doses of EPO?  What advantage may they gain from this?

XV. Heart
A. Atrial natriuretic peptide (ANP) – a hormone released when chambers of the heart are excessively stretched by high blood volume
1. Promotes sodium and water excretion at the kidney
2. Opposes effects of angiotensin II
3. Results in decreased blood volume/pressure

Thinking about the Heart in a role other than pumping blood
1. What are the differences between angiotensin II and atrial natriuretic peptide?  Under what circumstances might each be released?
2. How might ANP affect thirst?  Why?
3. Would hemorrhaging stimulate or inhibit the release of ANP?

XVI. Adipose tissue
A. Leptin – a hormone secreted by adipocytes during triglyceride synthesis
1) Leptin binds to hypothalamic neurons resulting in satiation
2) Leptin also must be present for gonadotropin synthesis

Thinking about Fat
1. What would you expect to see if a person had defective leptin receptors?
2. What would you expect if a person had a defective leptin gene?  How might you treat this person?  Would this treatment also be effective in question 1? Why or why not?

XVII. Stress Response (General Adaptation Syndrome, GAS)
A. Stress – anything that threatens homeostasis
B. 3 phases of GAS
1. Alarm phase
2. Resistance phase
3. Exhaustion phase
C. Alarm phase
1. Immediate response to stress
2. Sympathetic nervous system (SNS)
  a. Fight-flight
b. Adrenal medulla hormones
D. Resistance phase
1. Stresses that last longer than several hours
a. Starvation, severe anxiety, acute illness
2. Need for glucose by neural tissue (coordinated effort by following
events)
a. Hypothalamus produces CRH and GHRH
1) Release of GH and glucocorticoids
a) Fatty acids released by adipose (lipid reserves)
b) Glucose-sparing effect by other tissues
2) Glucocorticoids
b) Amino acids released by skeletal muscle
b. Gluconeogenesis by liver cells
1) Stimulated by glucagon and glucocorticoids
3. ADH and aldosterone maintain blood volume
a. Na+ and water conserved, K+ and H+ lost
4. Problems with the long-term resistance phase
a. Lipid reserves are exhausted (if starvation is the stress)
b. Side effects of resistance phase hormones
1) Compromised immune system due to long-term glucocorticoid involvement
2) Continued effects of ADH and aldosterone
a) Elevated blood volume/ pressure stresses
cardiovascular system
3) Inability to maintain glucocorticoid levels results in inability
to maintain glucose levels

E. Exhaustion phase
1. End of resistance phase and homeostasis breaks down (organ failure)
Thinking about GAS
1. Under what type of stress would ADH and aldosterone be an invaluable part of the resistance phase?
2. Although much of this system evolved to keep animals alive, under what kind of stresses in today’s society could this system actually be working against you?