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Endocrine System II. First, Let’s Compare Some General Aspects of the Nervous and Endocrine Systems. Nervous vs. Endocrine Systems. Communication nervous - both electrical and chemical endocrine - only chemical Speed and persistence of response

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nervous vs endocrine systems
Nervousvs. Endocrine Systems
  • Communication
    • nervous - both electrical and chemical
    • endocrine - only chemical
  • Speed and persistence of response
    • nervous - reacts quickly (1 - 10 msec), stops quickly
    • endocrine - reacts slowly (hormone release in seconds or days), effect may continue for weeks
  • Adaptation to long-term stimuli
    • nervous - response declines (adapts quickly)
    • endocrine - response persists
  • Area of effect
    • nervous - targeted and specific (one organ)
    • endocrine - general, widespread effects (many organs)
what is an endocrine axis
What is an Endocrine Axis?

This is a Relationship between the hypothalamus, pituitary and a more remote gland…………. There are Three:

  • Hypothalamic-Pituitary-Gonadal Axis
  • Hypothalamic-Pituitary-Thyroid Axis
  • Hypothalamic-Pituitary-Adrenal Axis
the hpa axis
REMEMBER the Dry Lab data analysis using stressed mice.

There was a control group of mice with a complete HPA.

Subsequent groups had variations with missing pieces of this axis.

The HPG and HPT axis each work in a similar manner

The HPA Axis
you only need a small amount
You Only Need A Small Amount
  • A Small Amount of Hormone Goes A long Way:

---One molecule activates thousands of enzymes molecules through a process called enzyme amplification

hormones are cleared by the liver
Hormones are Cleared By The Liver
  • AND…. Different hormones vary in their rates of clearance.
  • The rate of hormone removal is called the metabolic removal clearance rate (MCR).
  • The length of time required to clear 50% of the hormone is from the blood is the half-life.
  • Each hormone have a specific Half-life which differs due to different molecule structure, weight , whether it is bound or unbound to a transport protein.
target cells modulation of sensitivity
Target Cells Modulation of Sensitivity
  • Target cells can modulate (adjust) their sensitivity to a hormone.
  • Upregulation- A Cell increases the number of hormone receptors and becomes MORE SENSITIVE to a hormone.
  • Downregulation- A cell reduces its receptor number and become less receptive to hormone.
modulation of target cell sensitivity
Modulation of Target Cell Sensitivity
  • Long-term use of high pharmacological doses
    • bind to receptor sites of related hormones
    • target cell may convert to different hormone
paradoxical effects
Paradoxical Effects
  • A target cell can convert one hormone such as testosterone to estrogen, during its pharmacological use. This may have paradoxically, feminization effects!
hormone transport
Hormone Transport
  • Monoamines and peptides are hydrophilic
    • mix easily with blood plasma
  • Steroids and thyroid hormone are hydrophobic
    • 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
mechanism of hormone action
Mechanism of Hormone Action
  • Overall: HORMONES influence TARGET CELLS.
  • They are “ligands” to receptors on cell membranes.
  • Once bound, hormones alter cell activity by 1. altering plasma membrane potential ( opening ion channels) 2. stimulates synthesis of proteins ..usually regulatory such as enzymes or 3. either activates or deactivates enzymes. 4. Stimulates mitosis.
some differences between classes
Some Differences Between Classes
  • Steroids Hormones- Transported by carriers, as they are hydrophobic, are known to bind to the chromatin (DNA) and initiates transcription.
  • Protein/Peptide Hormones- Cannot penetrate cell membrane- These use 2nd messenger systems. AND they usually Activate/deactivate enzyme system that are there rather than create more.
steroid hormone action
Steroid Hormone Action

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TO PLAY

STEROID HORMONE ANIMATION

Figure 9.1a

nonsteroid hormone action
Nonsteroid Hormone Action

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TO PLAY

NONSTEROID HORMONE ANIMATION

Figure 9.1b

hormone interactions
Hormone Interactions
  • Most cells sensitive to more than one hormone and exhibit interactive effects
  • Synergistic effects
  • Permissive effects
    • one hormone enhances response to a second hormone
  • Antagonistic effects
what do we mean by a second messenger what is the first messenger
What Do We Mean BY a Second Messenger? What is the First Messenger?
  • Hormones the activate 2nd messengers work through a G-Protein.
  • The hormone bind to a receptor on the membrane (as usual) THIS IS THE 1st messenger.
  • But the 1st receptor Activates a G-PROTEIN which, in turn, activates the 2nd messenger which is often cAMP
hydrophilic hormones mode of action camp as second messenger
Hydrophilic Hormones: Mode of ActioncAMP as Second Messenger

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 2 nd and 3 rd messengers
Hydrophilic Hormones: Mode of ActionOther 2nd and 3rd Messengers

Hormones may use different second messengers in different tissues.

ii overview of the endocrine system
II. Overview of the Endocrine System
  • Organs and their hormones
  • Anatomy and Physiology of Selected Glands
  • Clinical Implications of Endocrine Malfunctions of Selected Glands
do other tissues besides the endocrine glands secrete hormones
Do Other Tissues, Besides the Endocrine glands, Secrete Hormones?
  • Adipose Tissue ( fat) , Stomach , the placenta and there are others secrete hormones but they are not exclusively endocrine glands
other organs not considered endocrine organs that secrete hormones
Other Organs Not Considered Endocrine Organs, That Secrete Hormones:

For Example : Kidneys are not endocrine glands but they produce erthropoietin, a hormone very important in blood formation. They also produce calcitriol ( a form of vitamin D) and renin.

going back a chapter 1 neural stimuli of endocrine glands
Going Back a Chapter…..1. Neural Stimuli of Endocrine Glands
  • Nerve impulses stimulate hormone release
  • Most are under control of the sympathetic nervous system (Remember the adrenal medulla takes the place of a postganglianic neuron)

Figure 9.2c

2 control of hormone release by negative feed back rarely pos feedback
2. Control of Hormone Release by Negative Feed back (Rarely Pos.Feedback)
  • Hormone levels in the blood are maintained by negative feedback
  • A stimulus or low hormone levels in the blood triggers the release of more hormone
  • Hormone release stops once an appropriate level in the blood is reached
3 hormonal stimuli of endocrine glands tropic stimuli
3. Hormonal Stimuli of Endocrine Glands ( Tropic Stimuli)
  • Endocrine glands are activated by other hormones

Figure 9.2a

4 humoral stimuli of endocrine glands see below
4. Humoral Stimuli of Endocrine Glands (See Below)
  • Changing blood levels of certain ions stimulate hormone release

Figure 9.2b

the hypothalamus
Part of the brain and connected to the pituitary gland. The hypothalamus maintains heart rate, body temperature, and water balance as well as regulating the activity of the pituitary gland which, in turn, affects the release of hormones.

It secretes oxytocin , ADH and releasing factors (regulates the hypophysis)

Without this gland the pituitary cannot function properly as it stimulate it.

The Hypothalamus
parathyroids
Yellow-brown glands, posterior to thyroid

Usually 4 of these

Arranged in thick, branching cords containing Oxyphils cells and Chief Cells

Oxyphils Cells- larger than chief cells , no hormone produced. No known function.

Chief Cells-PTH (Parathyroid Hormone) – This is the single most important hormone controlling the calcium; Stimulates osteoclasts digest some of the bony matrix to release calcium and phosphate into the blood.

Parathyroids
thyroid gland 3 hormones t3 t4 calcitonin
Follicular Cells

Thyroid Hormone (Thyroxin-T4) and Triidothyronine-T3) T-4 has 4 iodines bound, T3 has 3 iodine bound

The main function of T3 and T4 : INCREASING METABOLIC RATE

TH also plays a role in providing adrenergic receptors

Additionally : is a regulator of growth and development

Parafollicular Cell (C-Cells)

Calcitonin- This is a polypeptide hormone . Important in lowering blood Calcium and phosphate levels. Most important during childhood when skeleton is growing.

Acts on bone, kidney and other cells.

Calcitonin controlled via negative feedback with blood concentration.

Thyroid Gland(3 Hormones:T3,T4 ,Calcitonin)
if you have a thyroid hormone deficiency
Goiter- A swollen mass of thyroid tissue/gland resulting from its overstimulation WITHOUT production of viable thyroid hormone.If you have a Thyroid Hormone Deficiency
grave s disease
This time the Thyroid gland is OVERACTIVE and produces too much TH.

Person has an elevated metabolic rate, can be nervous, sweaty and losses weight despite great appetite.

Often a protrusion of eyes “Betty Davis Eyes”. More common in woman.

Treatment: Surgery; Radioactive I destroys some of thyroid cells.

Grave’s Disease
last time we define a second messenger system
Last time We Define A Second Messenger System:

Q: Which hormones use second

messenger systems?

Q: What do we mean by a second

messenger system?

Q: Which molecule do we ALWAYS find associated with this system? (It facilitates and can be thought of as a “messenger”?

Q; What is the first messenger?

Q: Can you think of examples of 2nd messengers?

hydrophilic hormones mode of action other 2 nd and 3 rd messengers1
Hydrophilic Hormones: Mode of ActionOther 2nd and 3rd Messengers

Hormones may use different second messengers in different tissues.

adrenal gland cortex
Adrenal Gland: Cortex
  • Cortex- OuterPortion, forms the bulk of the gland..
  • Arranged in 3 layers: zona glomerulosa, zonafasiculata; and zona retcularis
  • Produces corticosteroids, synthesized from cholesterol; Subclasses:1. Mineralcorticoids, 2. Glucocorticoids and 3. Gonadocorticoids
mineral corticoids
Mineral Corticoids
  • Mineralcorticoids-( mainly ALDOSTERONE)

Function: controls sodium retention in kidney tubules; Controls potassium loss in kidney tubules

  • Control: Angiotensin II , blood concentration controls aldosterone levels.
glucocorticoids
Glucocorticoids
  • Include: cortisol (hydrocortisol), cortisone, and corticosterone.
  • Functions:
  • 1. Influence energy metabolism by keeping blood sugar levels fairly constant hence the name “gluco’-corticord”. Increases Gluconeogenesis This is when non-carb.s are used to make glucose. Example: amino acids, fats are converted to sugars.
  • 2. Affect metabolism of all nutrients.
  • (Next Slide)
glucocorticoids zona fasiculata
Glucocorticoids ( Zona fasiculata)

4. Effects on Inflammation and Immune Function

Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they administered at pharmacologic doses, but also is important in normal immune responses. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases. A long-term consequence of glucocorticoids is that they suppress the immune system.

5.Decrease effect of stress( By helping to adapt to stress --including both physical and psychological)

6. Affect ACTH secretion

Control: Corticotropin Releasing Factor (CRF) from hypothalamus. ACTH from adenohypophysis.

addison s disease
Addison's disease is an endocrine or hormonal disorder that occurs in all age groups and afflicts men and women equally.

The disease is characterized by weight loss, muscle weakness, fatigue, low blood pressure, and sometimes darkening of the skin in both exposed and nonexposed parts of the body.( pigment changes result from overstimulation of melanocytes from ACTH )

Addison's disease occurs when the adrenal glands do not produce enough of the hormone cortisol

ADDISON’S DISEASE
cushing s disease
Cushing’s Disease
  • This is a HYPERSECRETION Of cortisol.
  • Usually caused by a tumor on the anterior pituitary gland.
  • Symptoms: Resemble those of an exaggerated response to stress;
  • Glucose metabolism is suppressed, whereas lipid reserves are mobilized. The neck and checks use fat reserves, take on a MOONFACE appearance.
  • Muscle weakness; lack of endurance. Stressed out feeling.
  • Treatment: remove tumor
adrenal medulla
Where:The middle tissue of adrenal gland is composed of chromaffin cells.

More Specifically: Chromaffin cells are interwieved with neurons that produce the catechoamines epinephrine

Functions: 1.increases heart rate and blood pressure 2. regulates the diameter of blood pressure 3. stimulates the contraction of smooth muscle 4. Increases blood glucose concentration

Control: sympathetic nervous system

Adrenal Medulla
adrenal medulla1
Adrenal Medulla
  • Hormone: Norepinephrine
  • Function: Constricts arterioles
  • Increases metabolic rate
  • Control Metabolic Rate
gonadocorticords zona reticularis
Gonadocorticords: Zona Reticularis
  • Little strip close to medulla that produces ANDROGENS, under control by ACTH.
  • Once in bloodstream, SOME of these androgens are converted to ESTROGEN
  • Adrenal ANDROGENS stimulate the development of pubic hair in boys and girls before puberty.
  • NOT IMPORTANT FOR MEN…BUT FOR WOMEN…..THESE androgens…build muscles, blood cell formation and support the libido!!
pancreas
Pancreas

In the Islets of Langerhans: There are Alpha , Beta Cells and Delta Cells.

Beta Cells-Produce INSULIN

Function: facilitates glucose across the glucose transport on plasma membrane to lower blood glucose level.

Control: blood glucose conc.

Alpha Cells: Produce Glucagon

Function: Increase Blood Glucose Level

Control: Blood Glucose Conc.

Delta Cells: Produce Somatostatin

Function: When glucose AND amino acids rise after a meal. (A High protein meal SLOWS DIGESTION) This is the hormone. Inhibits various digestive activities, but also functions to inhibit BOTH alpha and beta secretions; It is a panacrine secrecrine secretion. Less is known about this hormone’s overall function, however.

during low blood sugar
During, Glucagon is released by Low Blood Sugar . This Hormone is transported from the pancreas to the liver, where is works. This hormone converts stored glycogen into glucose and raises blood sugar. When you eat blood sugar will “turn on” insulin and “turn off” glucagon. During Low Blood Sugar
during high blood sugar after a meal
Pancreas is stimulated to release insulin which stimulates the cells to uptake glucose from blood.

Insulin also converts Excess glucose to glycogen(a polymer of glucose and thus a storage form) in the liver.

During High Blood Sugar (after a meal)
what is diabetes type i
What is Diabetes Type I
  • The Islets of Langerhans are destroyed and no longer produce Insulin: Usually during childhood teaching.
  • Insulin needs to be taken usually by injection
diabetes type ii
Diabetes Type II
  • This is called Insulin Resistance
  • Islets cells still produce Insulin but cells resist its effects
  • Epidemic rates today; thought to be caused by excess weight gain.
diabetes mellitus if not controlled properly
Diabetes Mellitus (if Not controlled Properly)

Cause kidneys to dilute the urine more….lose more water ; one becomes dehydrated. If one’s sugar rises too sharply…blurred vision, disorientation, muscle weakness.

IN THE LONG TERM:

Organs are ENERGY DEPLETED and start to ATROPHY; The eyes, kidney, heart

what is insulin resistance
What is Insulin Resistance?
  • Your cells resists the effects of insulin thereby requiring more of this hormone than normal. Diabetes type II results.
  • Effects of Diabetes if not treated: Blindness, kidney failure. Diabetes is also a risk factor which leads to arteriolosclerosis which can lead to strokes and/or heart attacks.
diabetes insipidus
Diabetes Insipidus
  • A disorder which develops when the posterior lobe of the pituitary gland no longer releases adequate amounts of ADH, or when the kidneys can no longer respond to ADH.
ovaries
Secrete : Estrogen

Develop Sex Organs and female Characteristics

Initiates Dev of follicles

Control : FSH

Ovaries
slide68

Follicle Stimulating Hormone (FSH)

  • ….Female:
  • Function:
    • Stimulates growth of ovarian follicle
    • Stimulates ovulation
  • Control:
    • Gonadotropin releasing hormone (GnRH)
slide69

Leutinizing Hormone (LH) …..Males:

    • Stimulates secretion of testosterone
    • Stimulates development of interstitial tissue of testes
  • Control:
    • Gonadotropin Releasing Hormone (GnRH)
slide70

Follicle Stimulating Hormone (FSH)

  • ….Female:
  • Function:
    • Stimulates growth of ovarian follicle
    • Stimulates ovulation
  • Control:
    • Gonadotropin releasing hormone (GnRH)
testes
Testes
  • Hormone: Androgens: TESTOSTERONE and Inhibin
  • Function: Dev of Sex Organs and Male Char. Aids Sperm Production
  • Control : LH
leptin
Leptin, a hormone secreted by the body’s fat cells.

Around 5-10% of overweight humans are probably deficient in leptin (Proc. Nat. Acad. Sci. 95: 11846, 1998).

LEPTIN
adipocytes and leptin
Adipocytes and Leptin

Leptin, via the hypothalamus, makes you feel full, satisfied. You stop eating.

ghrelin beware of what lines your tummy
Ghrelin: Beware of what lines your Tummy!
  • This is a hormone secreted by the lining of the stomach.
  • Ghrelin functions to increase hunger though its action on hypothalamic feeding centers. .
  • In experiments , humans injected with ghrelin reported sensations of intense hunger. Ghrelin also appears to suppress fat utilization in adipose tissue, SO…Too much Ghrelin is as true obesity culprit!.
thymus
Thymus
  • READ ABOUT IT
pineal gland
Pineal Gland
  • READ ABOUT IT