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BC3004: Cell Signalling > Intracellular Signalling Mechanisms of Steroids, Thyroxine & Retinoic Acid > Flashcards

Intracellular Signalling Mechanisms of Steroids, Thyroxine & Retinoic Acid Flashcards

1
Q

What type of molecules are Steroids and Thyroxines (thyroid hormone) and what type of receptor do they bind?

A
  • Hydrophobic
  • Bind intracellular receptors
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2
Q

What precursor are Steroids synthesised from?

A

Cholesterol

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3
Q

How is Thyroxine synthesised?

A
  • Iodination and coupling of two tyrosine molecules
  • Involves thyroglobulin
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4
Q

What is the general structure of a steroid?

A
  • based on sterol structure
  • four fused rings - three hexane rings (6 carbons) and one pentane ring (5 carbons)
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5
Q

TRUE OR FALSE:
The core structure of steroids is almost planar and is relatively rigid, and the fused rings do not allow rotation about the C-C bonds

A

True

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6
Q

How many naturally occurring steroids are there?

A

More than 200

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7
Q

How are steroids transported to target cells?

A

In the blood by carrier proteins such as albumin and globulin

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8
Q

TRUE OR FALSE:
Active hormones are stored for later use

A

False.
Little or no storage of active hormones

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9
Q

What type of regulation does synthesis of steroids and thyroxine undergo?

A

Negative feedback

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10
Q

What is the mechanism of action for steroids acting on their target cell?

A
  1. Released by carrier protein and crosses the plasma membrane
  2. Interact with receptor proteins to form a complex
  3. Complexes bind DNA sequences called response elements
  4. Steroid hormone / receptor complex functions as a transcriptional regulator up- or down-regulating gene transcription
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11
Q

Do steroids have a long or short duration of action?

A

Long duration of action
* effective from hours to days

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12
Q

Which drug is a potent synthetic analogue of the steroid Cortisol?

A

Dexamethasone

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13
Q

Which amino acid is Thyroxine based on?

A

Tyrosine

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14
Q

What are the TWO thyroid hormones?

A
  1. Thyroxine (T4)
  2. Tri-iodothyronine (T3)
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15
Q

Which hormone does the Thyroid mostly secrete?

A

T4

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16
Q

How is Thyroxine (T4) produced?

A
  • Endocytosis and intracellular proteolysis involving lysosomes
  • Involves proteolytic cleavage of the very large (2800 AA) precursor called thyroglobulin
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17
Q

TRUE OR FALSE:
Thyroxines are actively transported across the plasma membrane

A

True

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18
Q

What happens to Thyroxine (T4) when it is taken up by cells in the body?

A
  • Converted to more biologically active ‘de-iodinated’ T3 form
  • Binds the Thyroid hormone receptor and regulates transcription
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19
Q

Is reverse T3 (rT3) biologically active or inactive?

A

Biologically inactive

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20
Q

What is the blood plasma lifespan of thyroid hormones?

A

Several days
* effects last hours to days

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21
Q

What controls the production of the Thyroid hormones?

A

Under hierarchiacal control of the brain

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22
Q

What tripeptide is secreted by the hypothalamus in the production of Thyroid hormones?

A

Thyroid Releasing Hormone (TRH)

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23
Q

What is the mechanism of action of TRH?

A
  • TRH acts on the anterior pituitary causing it to produce a large glycoprotein called Thyroid Stimulating Hormone (TSH
  • TSH stimulates the thyroid gland to produce the thyroid hormones
24
Q

How is production of TSH regulated?

A

Feedback control by circulating unbound thyroid hormones

25
What can abnormal release of thyroxine by the thyroid gland affect?
Metabolism and lead to behavioural defects
26
How is OVERACTIVITY (Hyperthyroidism) of the tyroid characterised?
* Increased metabolism * Weight loss * Nervous and irritable personality
27
How is UNDERACTIVITY (Hypothyroidism) of the tyroid characterised?
* Decreased metabolism * Cold intolerance * Tiredness
28
What is Goitre?
Enlarged thyroid gland
29
How is Goitre treated?
Drugs such as **heparin & aspirin** can **increase free T4** blood concentrations
30
What is the function of Thyroxine?
Regulates body metabolism
31
What are Retinoids?
Hormone-like substances derived from retinoic acid (Vit. A metabolite)
32
What is the function of the steroid family of hormone receptors?
Act as **transcription factors** that regulate gene transcription
33
What THREE domains do steroid hormone receptors consist of?
1. N-terminal domain 2. DNA binding domain 3. Hormone binding domain
34
What are the characteristics of the N-Terminal Domain on steroid hormone receptors?
* Variable length * Low sequence homology between different receptors
35
What are the characteristics of the DNA Binding Domain on steroid hormone receptors?
* ~68 AA residues * Highly conserved * Binds to hormone response elements (HREs) near target gene
36
What are the characteristics of the Hormone Binding Domain on steroid hormone receptors?
* Intermediate sequence conservation (~225-285 AAs) * AAs which determine steroid binding may be over 100 residues apart
37
TRUE OR FALSE: Hormone binding is dependent on receptor secondary structure
False. It is dependent on TERTIARY structure
38
What is the mechanism of action of the Steroid Hormone Receptor?
* Steroid hormone receptor is either in the **cytoplasm** or **loosely associated with the nucleus** * Receptor is bound by molecular chaperone proteins like heat shock protein (HSP) that hold the receptor in the right conformation * HSPs dissociate and leave the receptor-hormone complex free to enter the nucleus and bind HREs in DNA to activate or repress gene transcription
39
Where are receptors for Thyroxine, Retinoids, and Vit. D3 located in the cell?
In the nucleus
40
What do receptors for Thyroxine, Retinoids, and Vit. D3 bind to in the nucleus?
HREs even in the ABSENCE of ligand (hormone) * act as transcription repressors
41
What does the binding of Thyroxine, Retinoids, and Vit. D3 to the receptor cause?
**Change in conformation** to allow them to **bind the transcription apparatus** * gene activation
42
How many binding sites does the receptor for glucocorticoid (GR) steroid hormone have?
4 - 6 binding sites (HREs) on DNA
43
What is the Glucocorticoid Response Element (GRE) and Estrogen Response Element (ERE) comprised of?
A pair of SIX nucleotide **palindromic** repeats, separated by any three bases
44
What do the DNA binding sites (HRE) for the estrogen, vit. D3, thryroid, and retinoic acid receptors consist of?
A pair of SIX nucleotide **direct** repeats, separated by any 3-6 nucleotides
45
How many C4 Zinc Finger Motifs do DNA binding domains contain?
Two
46
Which amino acids do Zinc Finger Motifs on the DNA binding domain contain?
2x Cys 2x His
47
What parts of the Zinc Finger Motif are often potent transcriptional regulators?
* Leucine Zipper * Basic Helix-Loop-Helix (bHLH)
48
What kind of Zinc Finger protein is the Glucocorticoid receptor?
Homodimeric C4 zinc finger protein
49
TRUE OR FALSE: Receptor expression is often under the control of other hormones
True. E.g. estrogens can induce the expression of the progesterone receptor
50
How are different subtypes of steroid hormone receptors generated?
From one gene by processes such as **alternate mRNA splicing**
51
How do Heterodimeric receptors increase diversity?
By the pairing of different monomers * allows receptor to have different activity to repress or activate a different gene
52
How is gene expression enhanced in steroid hormone regulation?
The presence of multiple HREs in the vicinity of the target gene
53
How do DNA binding proteins affect the action of hormone-receptor complexes?
They INHIBIT their action, particularly if they are bound close to the HRE
54
What are Accessory Proteins in the hormone-receptor complex?
Proteins which bind steroid hormone-type receptors can inhibit (co-repressors) or stimulate (co-activators) the action of transcription factors
55
What happens when transcription factors are targeted by protein kinases?
They are phosphorylated

BC3004: Cell Signalling (18 decks)

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