WEEK9 - module 3. Endocrinology

Learning objectives

 

Define hormones. What type of cells respond to hormones?

Chemical substances that secreted from glands and travels into interstitual flood to blood vessels ,and bind to target cell receptor. The receptor here only responds to specific hormone. 

 

Describe the different types of stimuli that cause hormone release.

Humoral, Hormonal, and Neural

-Humoral stimulus trigger hormone release in response to changing blood levels of certain critical ions or nutrients. (parathyroid hormone->Ca2+)

-Hormonal situmulus hormones are released by other hormones. (hypothalamus-> thyroid, adrenal cortex, gonads..)

-Neural stimulus trigger hormone release in response to neural input. (sympathetic nerves->adrenal gland)

 

Define autocrines, paracrines. ligands, agonists and antagonists.

-Autocrine

-Paracrine 

-Ligands : anything that can bind to receptors. 

-Agonists : binds to receptors and activates the cell

 

Distinguish between amino-acid and steroid hormones. What are eicosanoids?

Amino acids : water-soluble -> cannot pass through the cell membrane

Steroids (<-cholestrol) : lipid-soluble  -> pass through the cell membrane

Eicosanoids : lipid-soluble

 

When considering the interaction of hormones what do the terms permissiveness, antagonism and synergism mean?

(Interaction between hormones)

-permisiveness : allow other hormone to activated

-antagonism : the hormones that work in opposite way (insulin and glucagon)

-synergism : combination effect is greater than the sum of individual effect

(increasing blood sugar level - cortisol, insulin,epinephrine)

 

Describe how water-soluble and lipid soluble hormones exert their action on target cells.

-water soluble uses 2nd messengers 

1. binds to the transmembrane protein. it causes G protein to be active. 2. G protein activates enzyme(adenyl cylase)to produce cAMP (2nd messenger) 3. cAMP acts 

-lipid-soluble passes the membrane directly and make receptor-hormone complex in cytoplasm.

They move into nucleus and bind to DNA.

 

Describe how hormone actions are terminated.

-endocytosis of receptor-hormone complex

-acetylcholine estrase degrade hormone

 

Describe how vascular tone is controlled.

-vascular tone: flexibility of smooth muscle in blood vessels

-Noradrenaline-a receptors-constriction/ Adrenaline-b receptors-vasodilation

 

Understand the role of α and β receptors in the cardiovascular system, including the effects of β blockers

-a1) receptors-vasoconstriction

-b2) smooth muscles of blood vessels relaxation, bronchioles dilation

-b1) heart smooth muscle constriction

-b blockers work by blocking the effects of the hormone adrenaline, B blockers also help widen veins and arteries to improve blood flows

 

-selective b receptors needed to asthma patient

(Non-selective b receptor blocker can make hypertension of heart, high blood pressure (b1)

BUT it can also constrict bronchioles (b2))

 

Describe how bronchoconstriction and bronchodilation are controlled. 

-Noradre,Adre (Sympathetic)

bind to b2 receptors -> bronchiole dilation

-Noradre, Adre removed in parasympathetic taken away from b2 receptors

bronchiole constriction

 

 

 

 

 

PPT

 

 

 

 

Communication system

https://www.youtube.com/watch?v=Ry5fTZfZHIs 

 

Difference between nervous system and endocrine system 

IS

Nervous system uses electrochemical signals, which is Action potential and neurotransmitters. Nervous system is operated rapidly(ms). They are used in contracting muscles or stimulating glands with neurons. 

Endocrine system uses chemical substance, which is Hormone to send signals to body parts, and they are slow but last longer than electrical signal (min~). They control water balance, body temperature, stress, growth, reproduction, and so on.

 

 

 

 

 

 

 

Endocrinology

* Even if the gland is not connected to the nerves, the glands were secreting hormone into the blood

 

 

 

 

 

 

 

Major glands

*Thyroid gland : T3,T4, calcitonin

*Parathyroid gland : parathyroid hormone

*Adrenal glands : cortex-metalocorticoids(aldosterone), glucocorticoids(cortisol), gonadocorticoids(androgens)

                              medulla- adrenaline, noradrenaline

*Pancreas : glucagon(a cell), insulin(b cell), somatostatin (GHIH)(delta cell), pancreatic peptides(F cell) 

 

 

Hormones are secreted by ...

1. Humoral stimulus - the cell detect the concentration of ion (or the configuration of the blood) in the blood and secretes hormone

2. Neural stimulus - cell recieve action potential from the neuron and secretes hormone

3. Hormonal stimulus - One hormone stimulates another gland to secrete another hormone

 

 

 

 

 

 

 

Hormones defined

-Paracrine : locally sending the chemical signals

-Autocrine : secretes chemical signals and exerts on itself

-Endocrine : secretes hormone/chemical signals into the blood or lymph to bind to specific receptors in target cells

 

Autocrine and Paracrine are effecting cell locally. For autocrine, same cell release chemical signals and exert on it self. Releasing and receiving the signal happen on the same cell. Paracrine secretes chemicals in short distance, which is known as local diffusion. Endocrine is effecting cell in long distance. They secrete chemicals which travel in the blood and lymph to bind to specific receptors throughout the body.

 

 

 

 

 

 

 

 

 

 

 

 

 

Hormone action

Water soluble molecules cannot diffuse into the cell membrane which is hydrophobic. So the water soluble hormones need to bind receptors in the cell surface. Then it activates G protein in the cytoplasm and G protein in turn activates enzyme called adenylate cyclase. The enzyme activates 2nd messenger which can be cAMP or PIP. Then the 2nd messenger helps protein kinases. 

However, lipid soluble hormones can diffuse in the plasma membrane. They don't need any 2nd messenger. They bind to receptor protein directly in the cytoplasm and become hormone-receptor complex. Then they enter to the nucleus. By binding with the DNA, they initiate transcription and produce mRNA, which direct protein synthesis.

 

* How many different physiological responses can you list that might occur as a result of hormones binding to a target cell? 

-> They maintain water balance by controling electrolyte balance, manage sleep cycle, metabolism, growth and development of body tissues, human reproduction, and many other body functions. By altering membrane permeability and metabolic pathways, stimulating synthesis of proteins and enzymes, and activating hormone release.

 

Hormones may also be removed from the bloodstream by enzymatic activities present in the liver, or through excretion by the kidneys. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

How can 1 hormone can have multiple effects

 

*Which part of the nervous system is activated during a fight/ flight response? What are the other names for adrenalin and nor-adrenalin and where are they secreted from?

-> Sympathetic nervous system is activated. 

noradrenaline is secreted by the adrenal medulla and postganglionic axons of sympathetic nervous system. adrenaline is exclusively secreted by adrenal medulla.

 

<Cardiovascular responses in fight and flight>

*Will we need to increase or decrease blood pressure? 

We need to send blood rapidly to body parts to use energy in exciting, emergency, and embarrassing situations. So blood pressure will increase (the blood flow increase-> blood pressure increases)

 

*Will heart rate increase or decrease?

Heart rate will increase because it needs more contraction to increase blood rate and this in turn increases blood pressure.

 

*Will blood vessels in non-essential tissues/ organs, need to constrict or dilate?

Blood vessels in non essential parts will constrict. Because the blood needs to reach more essential body parts.

 

*Will vessels supplying the heart muscle itself and active skeletal muscle need to constrict or dilate?

Vessels supplying the heart muscle and the active skeletal muscle should be dialted. 

Heart needs to send more bloods to the body parts so their blood vessels should be dilated to increase the blood flow. The activated skeletal muscle need to recieve more blood from the dilated blood vessels so that they can source more oxygen and dipose waste products from the blood. 

 

*Will airways dilate or constrict?

The sympathetic nervous system stimulates bronchodilation, so the airways dilate.

 

*Blood vessels in the heart are therefore likely to have a preponderance of ?

beta1 receptors (heart muscle contraction)

 

*those in many of the rest of the non-essential tissues/organs ? receptors?

alpa receptors (a receptor bring about vasoconstriction) because they don't need much blood supply

 

*If airways dilation was desired, which sort of selective agonist/antagonist would be best? 

b1 receptors arise bronchodilation. b1 selective agonist would be best

 

*What effect could a non-selective agonist used to treat asthma have on heart function?

If non-selective b agonist is used in the treatment, it will act well in bronchodilation by the b1 receptors' activation, however, it also stimulates the b2 receptors so the heart constriction arise and the heart rate and blood pressure will increase. 

 

Which beta blocker would be best suited to treat asthmatics?

b1 blocker, heart should be not constracted, it should dilated to send more blood to the body parts to deliver oxygen.

b2 receptors function as bronchodilation so it doesn't need to be blocked.

(It was concluded that, in patients with asthma who require beta blockade, atenolol is the preferred agent, co-prescribed with a beta2 stimulant.)

 

 

 

Self paced quiz

 

1. Hormone is the chemical substances which are secreted by glands or specialised cells, and they travel into blood in order to bind to specific receptors to drive particular response. 

(Those specific response includes controlling permeability of membrane, stimulate 2nd messengers to alter activity, and protein synthesis)

 

2. Compare Neural and endocrine signals

Neural signals are transmitted in a form of action potential, which is an electrical signal. They are rapid and last for short. They send localised signals with neurons. 

Endocrine signals are transmitted by hormones, which are chemical signals. They are slow but last longer.  They send signals by secreting hormones with glands through blood plasma and 

Both neural and endocrine signals are used for communicating function between body parts. 

 

3. Compare Paracrine, endocrine and autocrine

Paracrine refers to localised diffusion of the hormone secreted by the cell affecting to the nearby cell. It is localised and rapid.

Endocrine is when the cell secretes the hormone into the blood cell and it travels to bind by the receptor of the target cell in the long distance.

Autocrine secretes the hormone and receives the hormone that it secreted by itself.

 

4. What is cytokines?

Cytokines are a broad and loose category of small proteins (~5–25 kDa[1]) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.

Cytokines include chemokines, interferons, interleukins, lymphokines, and tumour necrosis factors, but generally not hormones or growth factors (despite some overlap in the terminology). Cytokines are produced by a broad range of cells, including immune cells like macrophages, B lymphocytes, T lymphocytes and mast cells, as well as endothelial cells, fibroblasts, and various stromal cells; a given cytokine may be produced by more than one type of cell.[2][3] They act through cell surface receptors and are especially important in the immune system; cytokines modulate the balance between humoral and cell-based immune responses, and they regulate the maturation, growth, and responsiveness of particular cell populations. Some cytokines enhance or inhibit the action of other cytokines in complex ways. They are different from hormones, which are also important cell signaling molecules. Hormones circulate in higher concentrations, and tend to be made by specific kinds of cells. Cytokines are important in health and disease, specifically in host immune responses to infection, inflammation, trauma, sepsis, cancer, and reproduction.

 

 

5,6 How Water soluble molecule and Lipid soluble molecule elicit intercellular changes in target cells

 

As water soluble molecule cannot diffuse into the cell (they are polar and charged but the membrane is lipid soluble and non polar), 

Water soluble molecule hormone (1st messenger) binds to the transmembrane receptor outside of the cell.

The receptor activates G protein and it in turn activates adenylate cyclase (enzyme) to convert ATP into cAMP (cyclic adenosine diphosphate). cAMP is the 2nd messenger which send signals within the cell. 2nd messenger  activates protein kinase.

(glucagon, epinephrine,tsh,acth,calcitonin...)

 

Lipid soluble hormone acts on more direct way. It doesn’t need 2nd messenger. They can cross the plasma membrane and binds to receptor and complete receptor+hormone complex in the cytoplasm. Then, it enters the nucleus and bind to DNA HRE (hormone response elements), and start transcription. mRNA is produced by the transcription and it synthesise protein.

 

 

7. Compare agonist, antagonist, permissiveness, and synergistic effects

 

Agonist is the molecule that arise the physiological response to the receptor by binding on them.

Antagonist is the opposite with the agonist. They inhibit the receptor’s response by binding on them.

Permissiveness is the chemical that allow other molecules(hormones) to have physiological effect.

Synergistic effect means when the individual hormones work on same effect and make even greater effect than the sum of them working individually.

 

 

8. Vascular tone ? How is it achieved and functional importance?

 

Vascular tone refers the state of smooth muscle of blood vessels, whether they are dilated or contricted. They are important in controlling blood pressure and blood flow or rate. 

 

 

9. Noradrenalin, some blood vessels will contrict and others will dilate. Explain these phenomena in terms of receptors

 

Noradrenaline can effect different way depends on the receptors they bind with.

Alpa receptors, which are in most of the smooth muscle, control the constriction of the blood vessels when they bind with the noradrenaline. Contraction of a blood vessel means less blood flow. 

When they bind to the beta 2 receptors on coronary arteries and the skeletal muscle blood vessels, they dilate the blood vessels which allows more blood flows.

 

-Under normal, resting conditions do we need wide open airways? 

 

In resting condition, when it is parasympathetic situation, our airway usually narrow down than widely open. Our body doesn’t need that much of oxygen to function. However, when it is sympathetic situation, our body needs much energy to cope with that excited situation. So it needs wide open airways to receive oxygen to deliver to body tissues.

 

- What is the resting condition?

 

Digest, Defaecation, Diuresis !

In our resting condition, our body converts into rest and digest mode. It conserve energy uses. Heart rate slows down, blood pressure goes down, and bronchioles constrict. Our pupils are constricted and gastrointestinal motility increases.

 

 

-During an asthma attack bronchial constriction occurs and needs to be ameliorated. Sufferers might be treated with a,b agonist. Understand why

 

1. If asthma sufferers were provided with a non-selective b agonist, what would happen to their airways and what would happen to their heart rate?

 

Asthma surfferers need to breathe in more air  and need a better blood circulation to deliver oxygen to the body part. When the non-selective b agonist is provided, it binds on b1 receptor and arise bronchiodilation, which is good for them as it induce more breathe intake. However b2 receptors in the heart muscle are also activated which constrict the heat muscle. It slows down the blood flow which is not good for them as it becomes harder to deliver oxygen to body tissue.

 

 

2. Would be preferable to treat asthma sufferers with, a selective b 1 agonist, or a selective b2 agonist, and why?

 

Selective b1 agonist would be the best choice. (Along with the b2 antagonist) B1 receptor stimulate bronchiole dilation. b2 receptor stimulates heart constriction, so that it makes heart hypertension and heart beat and blood pressure can increase. 

 

 

 

a most blood vessel/ constrict

b1 heart muscle/ constrict

b2 bronchiole/ dilate

b2 coronary skeletal lung arteries/ dilate

 

 

Summary