W2L2 Endocrine regulations Flashcards by Aurora H

I. Basics
1. What are the 2 symptoms that could be associated with endocrine diseases?

Goiter - enlargement of the thyroid gland
Exoptalmos (the bulging of the eyeball anteriorly from the orbit)

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I. Basics - scientific approaches
2. Describe the experiment of Berthold in 1849

Removed testes from young male chicken
-> combs failed to grow
-> did not crow
-> didn’t try to mate with females
Preimplantation of testis to the abdominal cavity
-> the above changes are prevented/ reserved
=> Conclusion: the testis somehow “conditions” blood

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I. Basics - scientific approaches
3. Describe the experiment of Minkowski and Mering in 1889

Removed the pancreas from dog
Result: diabetes mellitus
=> There must be something that affect glucose

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I. Basics - Modern endocrinology
4. Describe the experiment of Starling and Bayliss

HCl to denervated jejunum
Intravenous administration of jejunal mucosa extract
=> These 2 things lead to pancreas secretion
=> Thus, Palov is not entirely right. Pancreatic secretion is not exclusively regulated by the nervous system => “chemical reflex”

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II. Hormone definition
1. What is the definition of hormone?

A chemical substance of low concentration, which is secreted to the blood by an endocrine gland and exerts its effect on distant target tissues

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II. Hormone definition
2. How is endocrine gland related to hormone?

Within endocrine glands, there will be…
- Maybe scattered cells (e.g, S cells -> secretin
- Neurocrine secretion (from neuronal axon terminals)
- Other cell types (e.g, atrial myocyte -> ANP)

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II. Hormone definition
3. How is BLOOD related to hormone?

Hormones are secreted to the blood
(e.g, testosterone secretion to blood and testicular ducts)

*** Hormones can be secreted to other places (NOT only Blood)

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II. Hormone definition
3. How is low concentration related to hormone?

In general, 10^-6 to 10^-12 mol/L (µM, nM, pM)
- High affinity detection -> hormone receptors
- Only cells with specific receptors can respond

Specificity, but:
+ 1 hormone -> several receptor types

+ More than 1 hormone -> 1 receptor type
+) due to similar chemical structure, concentration, etc.

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II. Hormone definition
4. Hormones can not undergo exocytosis.
-> T/F? Why?

False! They can be!
- Hormones are secreted (released)
- E.g, steroid hormones: NO EXOCYTOSIS

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II. Hormone definition
5. How is distant target tissue related to hormone definition?

Maybe another endocrine gland
In addition: paracrine, autocrine, intracrine effects
Many hormones (e.g, peptide, protein, biogenic amin) are also neurotransmitters in the CNS

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III. Function of hormones
1. What is the main function of hormones

Regulation of
- Homeostasis (stability of the internal environment
- Metabolism
- Growth/development (proliferation/ differentiation)
- reproduction

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III. Function of hormones - Theoretical background of endocrine regulations
2. What is the role negative feedback with hormone?

The hormone production stabilizes the function of the target organ (and hormone level)
- Low [hormone] -> increasing [hormone]
- High [hormone] -> decreasing [hormone]

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III. Function of hormones - Theoretical background of endocrine regulations
3. Negative feedback means that the “product” inhibits hormone synthesis
-> T/F? Why?

False! This is not always the case
Explain:
- The “product” also stimulates the gland (*target organ is constitutively active in the absence of the hormone)

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III. Function of hormones - Theoretical background of endocrine regulations
4. What is “sign-reversal”?

Odd number of the inhibitory interactions in the negative feedback loop

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III. Function of hormones - Negative feedback
5A. Give an example of negative feedback related to hormone in kidney?

Due to burn injury or eating bananas
-> Cells in adrenal cortex and zona glomerulosa stimulates aldosterone production
-> K+ excretion in kidney increases
-> Then, the amount of potassium decreases to normalize the balance
-> This will again stimulates cells in adrenal cortex and zona glomerulosa to produce aldosterone

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III. Function of hormones - Negative feedback
5B. Give an example of negative feedback related to hormone in pancreas beta-cells?

Eating chocolate
-> Cause an increase in [glucose]
-> increasing insulin production
-> increasing glucose uptake of tissues
-> effect: decreasing [glucose]

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≈ - Negative feedback
6. This is a technical model of the negative feedback
-> what does this tell us more than the classical model?

There is input signal. Input signal may change
There is amplification: the basis of precise regulation
- Small error signal -> large hormone response
- E.g, plasma [K+]: a few tenth of mM
[Ca2+]: a few hundredth of mM => precision of regulation

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III. Function of hormones
7A. What happen in the case of constant input signal and the perturbing effect?

A perturbing effect throws the regulated parameter off balance
The feedback signal deviates from the constant input signal
The increased error signal changes hormone release
The hormone restores the regulated parameter

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III. Function of hormones
7B. Make a schematic diagram in the case of the constant input signal and the pertubing effect

III. Function of hormones
8. What is the fate of the input signal?

The input signal is modified by the effects/regulation targeting the endocrine cell independent of the given negative feedback

III. Function of hormones
9A. What is the example that demonstrate the case “the input signal is modified by the effects/regulations targeting the endocrine cell independent of the given negative feedback?

Depending in vagus activity and composition of the gastric content, this feedback loop stabilizes acid production at different levels
THUS: normal function of the negative feedback does not mean in general that the regulated parameter is constant
There are also other “external” effects/regulations in addition to those acting on the G cell in the above negative feedback loop
(vagus, histamine -> parietal cell
vagus, gastric content -> D cell
Gastric content -> luminal pH, etc.)
Negative feedback loops may co-assemble (2 loops have 1 or more common components)

III. Function of hormones
9B. Examples of other “external” effects/regulations in addition to those acting on the G cell in the above negative feedback loop

Vagus, histamine -> parietal cell
Vagus, gastric content -> D cell
Gastric content -> luminal pH, etc.

III. Function of hormones
9C. Negative feedback loops may co-assemble
-> T/F?

True!
- Two loops have 1 or more common components

III. Function of hormones
10A. What are the characteristics patterns of negative feedback circuit integration, hormonal regulation at the organism level?

One hormone -> many functions (pleiotropic effects)
+) e.g, insulin -> skeletal muscle: glucose uptake
+) adipose tissue: lipogenesis, etc.
One function <- many hormones
+) e.g, blood [glucose] <- insulin, glucacon, GH

III. Function of hormones 10B. What is the "hierarchical" arrangement of of negative feedback circuit integration, hormonal regulation at the organism level?

III. Function of hormones 11A. What is positive feedback?

- A feedback that is much less frequent than the negative feedback - In general it works: +) in a given concentration range +) for a given time period - No "sign change"

III. Function of hormones 11B. What is are examples of positive feedback?

1/ Estradiol (E2) +) low concentration -> negative feedback (decreasing [LH]) +) high concentration -> transient positive feedback (increasing [LH]) 2/ increasing [oxytocin] -> increasing uterine contraction -> increasing cervix stretch -> increasing [oxytocin]

III. Function of hormones 12A. How do negative feedback and feed forward work together?

- In the case of the negative feedback, the perturbing effect is the cause of the regulation - If the regulation is slow compared to the perturbing effect then the regulated parameter fluctuates - In the case of the feed forward, the perturbing effect is not the direct cause of the regulation - "Wise foresight" is required that the pertubing effect is imminent - The fluctuation can be minimized by the appropriate timing of the regulation

III. Function of hormones 12B. Give an example of feed forward

Incretins

IV. General concepts of hormonal regulation 1. How does regulation of hormone production and secretion work?

1. Synchronized regulation of synthesis and secretion (at a "long" timescale production = secretion) 2. For some hormone, there is no storage/secretion 3. In many cases (protein and peptide hormones): prohormone is synthesized - Prohormone -> protease (or peptidase) converts it to active hormone - From one hormone -> distinct biological activity products - In different tissues -> different peptidases -> different products - a way of intracellular decomposition -> inactivation

IV. General concepts of hormonal regulation 2. What are characteristics of regulation of hormone storage?

1. Storage compensates for the transient inequality of production and release - Stores maybe substantial for some hormones - Significance + Emergency situation -> stored amount to circulation + Synthesis may depend on environmental factors +) e.g, thyroid hormones (T3, T4) - changing iodine intake +) D vitamin - intake or sunlight for production 2. For some hormones, there is no storage/ secretion

IV. General concepts of hormonal regulation 3A. What does the "biorhythm" of hormone secretion include?

- may depend on age - seasonal - monthly cycle - daily cycle - ultradian rhythm (hours, minutes)

IV. General concepts of hormonal regulation 3B. The "biorhythm" of hormone secretion may depend on age -> Give examples

- Sexual steroids (child, adolescence, adult, elderly) - Growth hormone (high in children, smaller in adults)

IV. General concepts of hormonal regulation 3C. Examples of seasonal cycle of "biorhythm" of hormone secretion?

Thyroid hormones (increase in the winter) - Less pronounced in humans (eskimo) - clearly in the reindeer

IV. General concepts of hormonal regulation 3D. Examples of monthly (e.g,) cycle of "biorhythm" of hormone secretion?

- Estradiol - Progesterone - LH - FSH => PERIODIC CHANGES

IV. General concepts of hormonal regulation 3E. Examples of daily (circadian) of "biorhythm" of hormone secretion?

E.g, 1. [cortisol] - high before waking up - minimum at midnight 2. [GH] - high after the beginning of sleep

IV. General concepts of hormonal regulation 3F. Examples of ultradian rhythm (hrs, mins) of "biorhythm" of hormone secretion?

Pulsatile/ episodic secretion

IV. General concepts of hormonal regulation 4A. What are characteristics of pulsatile secretion?

1. Important in the maintenance of sensitivity/ prevents desensitization 2. For some hormones - only the amplitude changes - both amplitude and frequency change

IV. General concepts of hormonal regulation 4B. Give an example of pulsatile secretion?

Pituitary hormones (oscillation depends on neural (CNS) mechanisms)

IV. General concepts of hormonal regulation 5. Give an example of the mechanism of the regulation of hormone release

IV. General concepts of hormonal regulation 6A. What are the 4 factors of the regulation of hormone sensitivity?

1. Changes of the receptor number 2. Changes of the receptor sensitivity (homolog and heterolog desensitization) 3. Changes of IC signaling pathway 4. Number of responsive cells, cell size, differentiation (in the target tissue)

IV. General concepts of hormonal regulation 6B. How do Changes of the receptor number affect the regulation of hormone sensitivity?

IV. General concepts of hormonal regulation 6C. How does number of responsive cells, cell size and differentiation (in the target tissue) affect the regulation of hormone sensitivity?

Typically - hormone -> trophic effects - lack of hormone -> atrophy - a special situation: changes of the endocrine gland in response to the exogenous administration of its hormone and to the abrupt withdrawal of the treatment (e.g, steroids)

IV. General concepts of hormonal regulation 7A. What does the permissive effect mean? What are its characteristics?

1. The effect is NOT proportional to the hormone concentration, but the hormone is indispensable for the effect 2. The permissive effect often relies on nuclear receptors of the hormone, which modify gene expression

IV. General concepts of hormonal regulation 7B. Give an example of permissive effect?

Beta-1 adrenergic recepor expression is permitted

IV. General concepts of hormonal regulation 8A. How does binding protein/hormone metabolism work?

IV. General concepts of hormonal regulation 8B. The role of binding protein

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W2L2 Endocrine regulations Flashcards

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