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Endocrinology > Hormone Synthesis & Action > Flashcards

Hormone Synthesis & Action Flashcards

1
Q

Describe the features of protein/peptide hormones

A

Water soluble, made from large precursor molecules – prohormones

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2
Q

Outline the features of steroid hormones

A

Steroids + iodinated tyrosines

Lipid soluble, made from low molecular weight precursors

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3
Q

How are protein/peptide hormones synthesised?

A

Transcription of DNA to RNA

Post transcriptional processing RNA 🡪mature RNA – excision of introns, modifications of 3’ and 5’ ends

Translation of mature RNA into protein using tRNA to transfer amino acids

Post translational processing cleavage of large pre-hormone, folding of proteins, addition of sugars (glycosylation)

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4
Q

What does a preprohormone consist of?

A

signal sequence + prohormone

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5
Q

What does a prohormone consist of?

A

active hormone + redundant sequence (inactive form of hormone)

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6
Q

What is teh role of the hormones signal sequence?

A

Enables hormone to know where to translocate to

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7
Q

Outline the synthesis of Insulin

A
  1. Transcription to mRNA
  2. Excision of introns to messenger RNA
  3. Removal of signal sequence and formation of disulphide
    bonds in RER
  4. Preproinsulin 🡪 proinsulin
  5. Transfer to Golgi apparatus, excision of C peptide and
    packaging into secretory granules
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8
Q

How is the hormone synthesis from cholesterol initiated?

A

Trophic hormone activates a membrane bound receptor
Initiates conversion of ATP → cAMP → PKA
CEH forms cholesterol

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9
Q

Where does hormone formation from cholesterol occur?

A

Cholesterol bound to sterol carrier protein - transported to mitochondria

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10
Q

What is a star protein?

A

StAR = steroidogenic acute regulatory protein

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11
Q

What is the role of the star protein?

A

transports cholesterol to inner mitochondrial membrane

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12
Q

Outline how the prohomrone is formed from cholesterol once in the mitochondria?

A

Cholesterol to pregnenolone by side chain cleavage enzyme, P450scc
Hydroxylase enzymes synthesise steroids between mitochondria and smooth endoplasmic reticulum

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13
Q

Which hormones does pregnenolone convert into?

A

Progesterone –> Aldosterone
17aOH Progesterone –> cortisol
–> Androgens –> oestrogens
via aromatase

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14
Q

What is the consequence of aromatase deficiency?

A

Unable to synthesise oestrogens from androgens 🡪 no epiphyseal closure 🡪 long stature

  • Virilisation of XX fetuses
  • Clitoromegaly
  • Ambiguous genitalia

Girls develop male-type characteristics and boys show early sexual development due to excess androgens

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15
Q

Outline the process of thyroid hormone synthesis

A
  1. Active uptake of iodide into follicular cell
  2. Oxidation of I- to Iodine by thyroid peroxidase
    (TPO)
  3. Iodination of tyrosine residues of thyroglobulin and
    apical-colloid interface
  4. Storage in colloid
  5. Uptake of thyroglobulin droplets into follicle cell
  6. Release and secretion of T3 and T4 stimulated by TSH
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16
Q

What is Goitre?

A

Enlargement of thyroid gland

17
Q

What is the consequence of goitre?

A

Antibodies to the TSH receptor act on the thyroid gland, stimulate excess thyroid hormones and can cause eye disease – Graves’ disease

18
Q

Which type of receptors do protein/peptide hormones bind to?

A

Protein and peptide hormones are water soluble (can’t pass through membrane) and bind to cell surface receptors:

  • GPCRs
  • Tyrosine Kinase domain associated receptors
19
Q

What is the effect produced by the binding of protein/peptide hormones to their cell surface receptors?

A

Activate second messengers/enzymes to cause cytoplasmic and nuclear effects

20
Q

Which receptors do steroid hormones bind to?

A

Steroid hormones are lipophilic (pass through membrane) requiring intracellular receptors in cytoplasm / nucleus
Their receptors are Transcription Factors (TF)

21
Q

What are the 2 major cell signalling pathways of tyrosine kinase receptors?

A
  1. Raf/MEK ERK1 pathway

cAMP → PKA → translocation to nucleus and transcription etc.
- mutations in this pathway can lead to cancer as the signalling molecules can act as oncogenes

  1. PI3 Kinase/AKT pathway

PIP2 → PIP3 leading to Ca2+ release

activated by growth factors (AKT aka PKB) - can also lead to cancer (nTOR is common target for cancer drugs)

22
Q

Summarise the JAKSTAT pathway

A

JAK stimulates STAT which is a TF that is translocated to nucleus to increase transcription

23
Q

Describe the adenyl cyclase secondary messenger pathway of GPCRs

A

AC -> cAMP -> PKA

24
Q

What is the effect of protein kinases in signalling pathways?

A

Kinases activate enzymes or can activate transcription factors

25
Q

Outline the Phospholipase C signalling pathway of GPCRs

A

Phospholipase C -> Kinase C -> DAG -> PKB

Phospholipase C -> IP3 -> Ca2+

26
Q

What are the signalling pathways of tyrosine kinase activity receptors?

A

Raf/MEK ERK pathway

PI-3 kinase/Akt pathway

JAK STAT pathway

27
Q

What effect does a defective GPCR have on endocrine functions?

A

Thyroid adenoma –TSH receptor (activating mutation)

Precocious puberty – LH receptor (activating mutation)

28
Q

What is the effect of a defective G protein?

A

McCune Albright syndrome (activating mutations of the G-protein)
Can involve excess hormone secretions
Fibrous dysplasia of bone
Cafe au lait skin pigmentation

29
Q

What is hyperthyroidism?

A

Activating mutation of the TSH receptor - a G-protein coupled receptor
Hyperfunctioning of thyroid

30
Q

What are steroid hormone receptors?

A

A family of transcription factors (either in cytoplasm / nucleus)

31
Q

What are domains?

A

Different functional regions of the receptor are defined as domains - A-F

32
Q

What is the C domain of steroid hormone receptors?

A

The C domain is the DNA binding region and is highly conserved

33
Q

Where does transcriptional activity occur on the steroid hormone receptor?

A

Both the A/B domains and E/F domains have transcriptional activity (AF-1/AF-2)

34
Q

Describe the structure of the steroid hormone receptor’s C domain

A

The DNA binding region is made up of 2 zinc fingers which can slot into the helix of the DNA

35
Q

Explain the outcome of steroid hormone receptor activation

A

Hormone crosses cell membrane
Heat shock protein dissociates from receptor

Hormone binds to receptor ; dimerization occurs
Dimerized receptors translocate to nucleus
Binds to hormone response element on DNA

Along with other TFs transcription is initiated
Some receptors located within nucleus not cytoplasm

36
Q

What is AIS?

A

Androgen Insensitivity Syndrome (AIS); when you can’t respond to steroid hormones
XY genotype, XX phenotype

Endocrinology (12 decks)

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