Hormone Synthesis and Action Flashcards Preview

Physiology 1 - SGUL (Sem 2) > Hormone Synthesis and Action > Flashcards

Flashcards in Hormone Synthesis and Action Deck (16)
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1
Q

What is the difference between protein hormones /peptide and steroid/iodinated tyrosine hormones?

A

PEPTIDES AND PROTEINS:

  • water-soluble
  • made from large precursor molecules - prohormones

STEROIDS AND IODINATED TYROSINES:

  • lipid-soluble
  • made from low molecular weight precursors
2
Q

As a recap (from FLC), describe the generalised scheme for the synthesis of protein/peptide hormones.

A

1) TRANSCRIPTION: of the DNA to RNA
2) POST-TRANSCRIPTIONAL PROCESSING: conversion of RNA to mature RNA with the excision of introns and modifications of the 3’ and 5’ ends
3) TRANSLATION: of mature RNA into protein using tRNA to transfer amino acids
4) POST-TRANSLATIONAL PROCESSING: cleavage of large-prehormone, folding of proteins, an addition of sugars (glycosylation)

3
Q

What is the difference in structure between preprohormones and prohormones?

A

The preprohormone contains the HORMONE, in addition to a SIGNAL SEQUENCE that allows the protein to be processed within secretory granules, and a REDUNDANT SEQUENCE, both of which will later be cleaved off.
The prohormone only contains the HORMONE and the REDUNDANT SEQUENCE.

4
Q

Describe the hormonal control of steroid synthesis from cholesterol.

A

A trophic hormone will activate a G-coupled protein receptor, which will activate a secondary messenger pathway (in this case, cAMP) which increases the amount of Protein Kinase A.
In this case, Protein Kinase A does two things. First, it increases the cholesterol ester hydrolase activity, which releases cholesterol from its cytoplasmic store. The second thing it does is that it increases the synthesis of a protein called StAR (Steroidogenic Acute Regulatory protein). This protein is responsible for transporting cholesterol from the cytoplasm to the inner mitochondrial membrane (this is a rate limiting step).

There, cholesterol is cleaved into an important molecule called Pregnenolone by the side chain cleaving enzyme, P450scc (this is also a rate limiting step). Pregnenolone is a precursor to alot of of other steroids hormones.

Between the mitochondria and the smooth endoplasmic reticulum, the steroids are synthesised by hydrolase enzymes.

5
Q

Describe the synthesis of thyroid hormones.

A

1) Upon the stimulation of the thyroid stimulating hormone (TSH), there is the active uptake of iodide into the follicular cell.
2) The iodide moves through the apical membrane via a transporter called pendrin, where it is oxidised to an iodinated intermediate by thyroid peroxidase (TPO), an enzyme activated by H2O2.
3) All together, all these components iodinate a thyroglobulin molecule (on the tyrosine residues, either mono or di). We can view thyroglobulin as the molecules that provide the tyrosine residues.
4) There is then the coupling (combining) of the iodinated residues to make T3 or T4.
5) The T3 /T4 are then stored in the colloid.
6) When stimulated by TSH (for example), there is the release and secretion of T3 and T4 into the blood circulation.

6
Q

Describe the diseases where you have an overactive thyroid gland, and where you have faulty receptors.

A

Goitre is when there is the overactivity of the thyroid gland, where the thyroid gland swells up.

Grave’s Disease is when you have a faulty, overactive receptor. Antibodies to the TSH receptor act on the thyroid gland, stimulating excess hormones. This can also cause eye disease.

7
Q

What are the differences between the cell signalling receptors for protein/peptide hormones and steroid hormones?

A

PEPTIDE/ PROTEIN HORMONES:
They are water-soluble, so they act on cell-surface receptors. This activates second messengers and/or enzymes; these have cytoplasmic and nuclear effects.

STEROID HORMONES:
They are lipophilic, so they act on intracellular receptors in the cytoplasm or nucleus. The receptors are transcription factors.

8
Q

What are the two types of cell receptors for protein/peptide hormones?

A
  • G-protein coupled receptors

- receptors with/ associated with tyrosine kinase domains

9
Q

What are the (5) different types of cell signalling pathways for protein/peptide hormones?

A
  • adenylyl cyclase and cAMP signalling pathway (GPCR)
  • phosphoinositide (PIP3) signalling pathway (GPCR)
  • Raf/MEK/ERk1/2 signalling pathway (TYROSINE)
  • phosphatidylinositol kinase/AKT signalling pathway (TYROSINE/ GPCR)
  • JAK/STAT signalling pathway (TYROSINE)
10
Q

Describe the Raf/MEK/ERK1/2 signalling pathway.

A
  • ligand binds to the tyrosine kinase receptor, receptor dimerises, receptor gets phosphorylated
  • in a series of events (via Grb2 and Sos), Ras GTP is activated, which activates Raf
  • activated Raf activates MEK, which activates ERK1/2
  • activated ERK1/2 enters the nucleus and initiates transcription
11
Q

Describe the phosphatidylinositol kinase/AKT signalling pathway.

A
  • ligand binds, dimerisation of the receptor
  • PI3-kinase activates PIP2 and PIP3
  • PIP3 activates Akt (Protein Kinase B)
  • Akt activates mTOR (mammalian target of rapamycin)
  • mTOR promotes ribosome production, stimulating protein synthesis
  • it also inhibits protein degradation and stimulates nutrient uptake and metabolism
12
Q

Why is it important to know about receptors and their signalling pathways?

A

It’s important to understand endocrine disorders and to provide targets for the development of new drugs.

13
Q

List some endocrine disorders that are associated with mutations in the receptor or associated G-protein.

A

DEFECTIVE G-PROTEIN COUPLED RECEPTOR:

  • Thyroid Adenoma - TSH receptor (activating mutation)
  • Precocious Puberty - LH receptor (activating mutation)

DEFECTIVE G-PROTEINS:
- McCune Albright Syndrome, in which Adenylate Cyclase is always “on” (activating syndrome) (can involve excess hormone secretions, fibrous dysplasia of bone and cafe au lait skin pigmentation)

14
Q

Describe steroid hormone (nuclear) receptors.

A

Steroid hormone receptors are a family of transcription factors. Different functional regions of the receptor are defined as domains (A-F):

  • the A/B domain is the N-terminal domain
  • the C domain is the DNA binding region and is highly conserved
  • the D domain is the hinge region
  • the E domain is the ligand binding domain
  • the F domain is the C-terminal domain

Both the A/B and E/F domains have transcriptional activity (AF-1/AF-2).
Different steroid receptors are continually being discovered.

15
Q

What is a steroid hormone’s C domain made up of?

A

The DNA binding region is made up of two zinc fingers which can slot into the helix of the DNA.

16
Q

How does a steroid hormone act on its cytoplasmic receptor?

A

1) Since its a steroid hormone (lipophilic), it can pass through the cell membrane.
2) The hormone will make the heat shock protein (HSP) (that is sitting in the steroid receptors (SR’s) place) dissociate and will take its place, causing dimerisation to occur.
3) The dimerised SRs will translocate to the nucleus, where they bind to the steroid response element (SRE) on the DNA.
4) Along with other transcription factors, transcription is initiated.

(some receptors are located within the nucleus, not the cytoplasm)

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