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Gateway > TLC - L2 - Cell signalling 2 > Flashcards

TLC - L2 - Cell signalling 2 Flashcards

1
Q

Where in the body are steroids synthesized?

A
  • Adrenal Cortex.
  • Testis.
  • Ovaries.
  • Placenta.
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2
Q

In what organel does steroid synthesis take place?

A

Mitochondria.

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3
Q

What kind of molecules are steroids?

A

Lipids.

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4
Q

Describe the structure of cholesterol?

A
  • 3 six membered ring.
  • 1 five membered ring.
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5
Q

What are the 4 main classes of steroids?

A
  • Corticosteroids.
  • Progestagens.
  • Androgens.
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6
Q

What is the most active class of steroid?

A

Androgens.

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7
Q

What is SF-1?

A

Transcription factor.

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8
Q

What does stAR stand for?

A

Steroidogenic acute regulatory protein.

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9
Q

What is stAR?

A

A Transport protein.

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10
Q

What does stAR do?

A

Transports cholesterol into the mitochondria.

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11
Q

What is CYP19?

A

Gene that codes for the aromatase cytochrome P450 enzyme.

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12
Q

What is the rate-limiting step in the production of steroid hormones?

A

stAR.

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13
Q

What is CREB?

A

Transcription factor.

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14
Q

What does CREB do?

A

Increasing or decreases transcription.

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15
Q

What does CREB stand for?

A

cAMP response element binding.

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16
Q

What steroids are produced in thecal cells?

A

Estradiol precursors.

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17
Q

Where are the steroids produced in thecal cells transported?

A

Granulosa cells.

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18
Q

Which oestrogen biosynthesis pathway takes place in both males and females?

A

1

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19
Q

What is GnRH?

A

Gonadotropin-releasing hormone.

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20
Q

What is gonadatropin?

A

Peptide hormones secreted by gonadotrope cells.

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21
Q

What are the 2 main types of gonadatropin?

A
  • Luteinizing hormone (LH).
  • Follicle stimulating hormone (FSH).
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22
Q

What kind of effect does oestrogen have on GnRH?

A

Increased secretion.

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23
Q

What kind of action is oestrogen driving an increase in GnRH?

A

Endocrine signalling.

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24
Q

Can steroids pass through the cell membrane?

A

Yes - they are hydrophobic lipids.

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25
Q

Where are the steroid receptors found?

A

Cytoplasm or nucleus.

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26
Q

What is the function of a chaperone protein?

A

Prevent synthesised polypeptide chains and assembled subunits from aggregating.

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27
Q

Where in the cell are oestrogen receptors found?

A

Within the nucleus.

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28
Q

What kind of receptor is the ER?

A

Ligand-activated transcription factor.

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29
Q

What happens when the ER forms a dimer?

A

It binds response elements in target gene promoters.

30
Q

What does the ER regulate?

A
  • Protein levels - through translation.
  • Position within the cell - through translocation.
31
Q

Is estradiol found in men or women?

A

Both.

32
Q

What is the ER?

A

Estrogen receptor.

33
Q

What is E2?

A

Symbol for oestradiol.

34
Q

What is estradiol (E2) ?

A

A major estrogen produced in the ovaries or via aromatase pathway.

35
Q

What are the 6 biological roles of E2?

A
  • Fertility.
  • Lordosis behaviour - sexual responsiveness.
  • Neurogenesis - maintaining brain function.
  • Cardiovascular.
  • Bone strengthening.
  • Reduces incidence of some tumours.
36
Q

What effects does E2 have in bone?

A
  • Stimulates growth hormone secretion - this regulates bone growth.
  • Promotes bone formation (rather than resorption) - by reducing osteoblast and osteoclast production.
37
Q

What effects does E2 have on the cardiovascular system?

A
  • Regulates nitric oxide.
  • Increases coronary flow.
  • Increases cardiac output.
  • Reduces fats in the blood.
38
Q

What is cardiac output?

A

The amount of blood the heart pumps through the circulatory system in a minute.

39
Q

What is coronary flow?

A

Movement of blood through the vessels of the heart, specifically from the ascending aorta.

40
Q

How can cardiac risk (heart disease) due to menopause be treated?

A

Hormone replacement therapy.

41
Q

What is P450 aromatase?

A

Enzyme required for the biosynthesis of estrogen.

42
Q

What is cytochrome P450?

A

A group of enzymes required for steroidogenesis.

43
Q

How can breast cancers be treated?

A

Inhibiting P450 aromatase expression - inhibits the production of estrogens.

44
Q

What is VEGF?

A

Signal protein that stimulates vasculogenesis and angiogenesis.

45
Q

What does VEGF stand for?

A

Vascular endothelial growth factor.

46
Q

What is angiogenesis?

A

Developing new blood vessels.

47
Q

What are the different kinds of angiogenesis?

A
  • Sprouting.
  • Intussusceptive/splitting.
48
Q

When does angiogenesis occur?

A
  • Wound-healing.
  • Monthly cycle (females).
  • Building of the placenta.
49
Q

What differences can be observed between the VEGF isoforms?

A

Different isoelectric points - acidic ranges.

50
Q

What is a homodimer?

A

A molecule composed of paired identical proteins.

51
Q

How is VEGF made biologically active?

A

Proteolytic cleavage by proteases.

52
Q

Why do tumours generate proteases?

A

So that they activate more VEGF and so that more angiogenesis takes place.

53
Q

What factors increase VEGF expression?

A
  • Hypoxia (low O2).
  • Myocardial ischaemia.
  • Cytokines and growth factors.
  • Cell differentiation.
  • Tumour induction.
  • Oncogenes.
54
Q

What oncogenes mediate VEGF expression?

A

ras and raf.

55
Q

What hormone leads to more expression of VEGF in granulosa cells?

A

Luteinising hormone.

56
Q

What kind of receptors does VEGF bind to?

A

Receptor tyrosine kinase.

57
Q

What is an SH2 domain?

A

Src homology 2 - sequence-specific phosphotyrosine-binding module present in many signaling molecules allow autophosphorylation.

58
Q

Outline signalling initiation of receptor tyrozine kinases?

A
  1. Ligands bind to the receptor - stable dimers are formed.
  2. Receptor activation occurs - autophosphorylation is stimulated.
  3. Signalling complex formed - intracellular proteins containing SH2 regions bind to phosphotyrosin.
59
Q

What is autophosphorylation?

A

Process in which a phosphate is added to a protein kinase.

60
Q

What kind of molecules have SH2 domains?

A

Intracellular proteins.

61
Q

Even though SH2 domains may bind the same receptor tyrozine kinase, can they activate different pathways?

A

Yes.

62
Q

What happens to mice heterozygous for VEGF?

A

die in utero.

63
Q

What effect does removing VEGF have?

A

Increased mortality and stunted body growth.

64
Q

What effect does VEGF have on hepatic cells?

A

Protects them from apoptosis and causes proliferation.

65
Q

What is vasculogenesis?

A

Formation of the vascular (blood) network in the embryo.

66
Q

What effect does VEGF have on the kidney?

A

It regulates the function in the glomerulus - removal results in renal disease.

67
Q

What effect does VEGF have on bone formation?

A

Promotes longitudinal bone growth.

68
Q

What role does VEGF play in endocrin glands?

A

Regulates follicular development and corpus luteum generation.

69
Q

What type of cancers secrete a lot of VEGF?

A

Carcinomas - malignant cancers.

70
Q

What other conditions (not cancer) show an increase in VEGF expression?

A
  • Eye disorder.
  • Inflammatory disorders.
  • Endometriosis + PCOS.
71
Q

What treatments are applied to patients with disorders associated with high VEGF?

A
  • Anti-VEGF monoclonal antibodies.
  • Co-treatment with chemotherapy.
72
Q

What does low levels of VEGF in spinal cord neurons lead to?

A

Sclerosis.

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