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Intercal - Advanced molecules, membranes and cells > Endocrine Signalling 1 > Flashcards

Endocrine Signalling 1 Flashcards

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Organic Chemistry 101 flashcards
1
Q

What do ligands do

A

Switch on nuclear receptors

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2
Q

What is similar in the structure of ligands

A

Have aromatic rings

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3
Q

What’s the purpose of these aromatic rings found in ligands

A

Lipid-soluble - so can enter the cell through the plasma membrane and act on site, might also need to go through the nucleus

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4
Q

What imaging is used to look at endocrine signalling

A

X-ray Crystallography

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5
Q

What are the three types of negative feedback loops

A

Long feedback
Short feedback
Ultra short

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6
Q

What happens with the hormone cascade regarding the amount of factor

A

The concentration of release gets larger -
Neurotransmitter to environmental change (nG)
Hypothalamus releasing hormone (nG)
anterior pituitary trophic hormones (microgram)
Hormone (milligram)
Effect

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7
Q

What is the structure on what steroid hormones are built

A

CCCP nucleus - cyclopentanoperhydrophenanthrene (sterane)

Also known as cholesterol

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8
Q

How are different steroid hormones structured?

A

All have CCCP but have extra groups added to make different hormones - oestrogen, progesterone, cortisol etc

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9
Q

How are steroid hormones formation triggered extracellularly

A

Ligand binds to its g-protein receptor which triggers -

Calcium is released from the endoplasmic reticulum to increase calcium levels in the cell
cAMP release

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10
Q

How are steroid hormones formed

A

The cell has a lipoprotein receptor that activates cholesterol ester droplets in the cell.
These cholesterol esters enter the mitochondria and start to be made into cortisol
StAR protein is needed to get the cholesterol ester into the mitochondria

Found mostly in mitochondria and endoplasmic reticulum

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11
Q

How are steroid hormones broken down

A

Difficult as no structure in the body is able to break down CCCP therefore it is made more water-soluble for renal excretion

Makes more water-soluble by adding hydroxy or keto groups

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12
Q

What generates thyroid hormones

A

Amino acids - tyrosine and iodine atoms attached (T3 and T4)

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13
Q

How do thyroid hormones trigger intracellular processes

A

Bind extracellularly to G protein-coupled receptor.

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14
Q

What is the essential enzyme for thyroid hormone formation

A

thyroperoxidase - takes iodide ion to form iodine and then attach them to tyrosine to make MIT or DIT

DIT X2 - T4
DIT +MIT - T3

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15
Q

What is important about thyroid hormones regarding their formation

A

The way round they’re joined (DIT/MIT) determines if they’re active or not

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16
Q

Where is tyrosine found

A

In thyroglobulin vesicles - strong oxidase reactions to get out of these vesicles

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17
Q

Give the underlying process for T3 and T4 formation

A

Strong oxidative reaction to getting tyrosine out of these vesicles.
This is the reason that this happens outside the thyroid cell then renters via endocytosis and cleaved by proteases to release T3 and T4 in the bloodstream. This is to

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18
Q

What is deiodination

A

Removal of iodine atoms.

Can activate (T4 –> T3) - T3 is more active than T4

Can deactivate - T2 or T1

19
Q

How do steroid hormones activate their specific nuclear receptors

A

Steroid enters cell from blood and gets through due to lipophilic.
In the cytoplasm, steroid hormone receptors are present waiting for the ligand to arrive.
They are held in place by shaperones and the ligand binds to receptor and activates it.
The receptor enters the nucleus and binds to DNA, acting as a transcription factor to promote transcription of mRNAs
These mRNAs are translated into protein at the ribosomes.

20
Q

How do non-steroid hormones activate their specific nuclear receptors

A

These hormone receptors are already in the nucleus, waiting for the non-steroid hormone to enter the cell followed by the nucleus

The receptor binds to DNA, acting as a transcription factor to promote transcription of mRNAs
These mRNAs are translated into protein at the ribosomes.

21
Q

What is the 3 important structures of nuclear receptors

A

Ligand binding domain

DNA binding domain

Unique N-terminal domain (NTD)

22
Q

What 3 processes do nuclear receptors do

A

Dimerization
Interaction with chaperones (getting in and out of nucleus)
Interaction with co-regulators (other proteins for transcription factor role)

These can be manipulated with phosphorylation or other groups

23
Q

What is the function of the ligand binding domain

A

Forms a ligand-binding pocket that restricts what can bind

24
Q

What is the function of the DNA binding domain

A

has 8 cysteine residues which form zinc fingers which are needed for binding the nuclear receptor to the DNA
It also has C-terminal extension which binds to DNA too

25
Q

What is the function of the Unique N-terminal domain (NTD

A
  • most variable section of many AA. Has an area called the activation function 1 (AF1). Vital for it to work as a transcription factor. The hinge region is a flexible region which is used to change the shape of the protein to expose previously unexposed amino acids and change their function.
    (e.g. bind the ligand)
26
Q

What facilitates the uptake of the steroid hormone into the nucleus once bound to its receptor in the cytoplasm

WIDER READING - Mahato et al (1999)

A

Nuclear localization sequence - amino acid sequence that tags a protein to allow it to be taken into the cell nucleus by nuclear transport.

Different nuclear receptors can share the same NLS.

27
Q

What binds to hormone receptors while no hormone is present

WIDER READING - Walter S, Buchner J (April 2002)

A

Heat shock proteins

28
Q

What are the two main forms of nuclear receptor protein

WIDER READING - Novac N, Heinzel T (Dec 2004).

A

Type 1 - HSP binds and found in cytoplasm
Type 2 - no HSP and found in the nucleus

29
Q

What are the non-genomic effects of steroid hormone binding and give an example

WIDER READING - Luconi 2004

A

Showed changes in human sperm as a result of oestrogen and progesterone which were too quick to be genetic transcirption and translation -

Changes seen - calcium influx, tyrosine phosphorylation, cAMP increase, hyperactive motilty.

Done western blot analysis to identify mPR and mER on sperm which are allowing progesterone and oestrogen to bind and cause these rapid effects.

30
Q

How many nuclear receptors do humans have

WIDER READING - Zhang et al 2004

A

48, 24 of which are transcription dependent factors.

31
Q

Give some examples of type 1 receptors

WIDER READING - Linja 2004

A

Glucocorticoid receptor
Progesterone receptor
Androgen receptor
Estrogen receptor

32
Q

What is the difference about the receptor type 1 and 2 structure

WIDER READING - Amoutzias et al 2007

A

Type 1 - homodimers
Type 2 Hetrodimers

33
Q

Give some examples of type II nuclear receptors

Wider reading - Klinge 1997

A

Retinoic acid receptor
Retinoid X receptor Thyroid hormone

34
Q

What do coactivators contain and how do they work

WIDER READING - sterner 2000

A

Agonist ligands bind causing a conformational change in the receptor to form coactivator proteins - contains an intrinsic histone acetyltransferase which weakens histone-DNA associated which promotes gene transcription

35
Q

What do corepressors contain and how do they work

Wider reading - seo-hee you 2013

A

An antagonist ligand binds which causes a conformational change in the receptor which makes it more likely that corepressor proteins will bind. When they bind, these proteins recruit histone deacetalyases which strengthen DNA-histone association which stops gene trasncription.

36
Q

Name two important enzymes for steroid formation
WIDER READING
- Schiffer 2019

A

Two major enzymes involved are cytochrome P450 and hydroxysteroid dehydrogenase.

37
Q

What is the free hormone hypothesis

WIDER READING - Mendel 1989

A

Hormone is only biologically active if unbound from a protein in the plasma.

38
Q

How are steroid hormones believed to take in sex hormones
WIDER READING - Hammes 2005

A

Steroid binds to megalin (membrane receptor) and enters the cell via endocytosis where this complex goes to the lysosome and is degraded to leave the steroid to go into the cytoplasm and bind to its target receptor.

39
Q

How are peptide hormones synthesized

WIDER READING - Bowen 2019

A

Via the endoplasmic reticulum where they are transferred to the golgi apparatus and put into secretory vesicles for exocytosis. From this they can be excreted by 1 of these pathways -

Regulated secretion
Constitutive secretion

40
Q

What is regulated secretion

WIDER READING - Bowen 2019

A

Peptide hormone released in burst from vesicles when stimulated. Most common.

41
Q

What is constitutive secretion

WIDER READING - Bowen 2019

A

Continually secreted as it is synthesized

42
Q

What is the rate limiting step of all steroid hormones

WIDER READING - Bowen 2019

A

Cholesterol to pregnenolone (formed in mitochondria)

43
Q

What is the only nuclear receptor and ligand structure that has been structurally solved

WIDER READING - Helsen 2012

A

Retinoid receptor

44
Q

What did this study show regarding the structure of the androgen receptor

WIDER READING - Helsen 2012

A

Mutations occurred in the ligand binding domain and DNA binding domain separately, they had effects on each others binding capabilities but not their own, showing that the areas of mutation are key for communication between each of the two binding domains. These mutations were associated with androgen insensitivity therefore may represent some of the genetic background for this syndrome.

Intercal - Advanced molecules, membranes and cells (31 decks)

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