TLC - L2 - Cell signalling 2 Flashcards
1
Q
Where in the body are steroids synthesized?
A
- Adrenal Cortex.
- Testis.
- Ovaries.
- Placenta.
2
Q
In what organel does steroid synthesis take place?
A
Mitochondria.
3
Q
What kind of molecules are steroids?
A
Lipids.
4
Q
Describe the structure of cholesterol?
A
- 3 six membered ring.
- 1 five membered ring.
5
Q
What are the 4 main classes of steroids?
A
- Corticosteroids.
- Progestagens.
- Androgens.
6
Q
What is the most active class of steroid?
A
Androgens.
7
Q
What is SF-1?
A
Transcription factor.
8
Q
What does stAR stand for?
A
Steroidogenic acute regulatory protein.
9
Q
What is stAR?
A
A Transport protein.
10
Q
What does stAR do?
A
Transports cholesterol into the mitochondria.
11
Q
What is CYP19?
A
Gene that codes for the aromatase cytochrome P450 enzyme.
12
Q
What is the rate-limiting step in the production of steroid hormones?
A
stAR.
13
Q
What is CREB?
A
Transcription factor.
14
Q
What does CREB do?
A
Increasing or decreases transcription.
15
Q
What does CREB stand for?
A
cAMP response element binding.
16
Q
What steroids are produced in thecal cells?
A
Estradiol precursors.
17
Q
Where are the steroids produced in thecal cells transported?
A
Granulosa cells.
18
Q
Which oestrogen biosynthesis pathway takes place in both males and females?
A
1
19
Q
What is GnRH?
A
Gonadotropin-releasing hormone.
20
Q
What is gonadatropin?
A
Peptide hormones secreted by gonadotrope cells.
21
Q
What are the 2 main types of gonadatropin?
A
- Luteinizing hormone (LH).
- Follicle stimulating hormone (FSH).
22
Q
What kind of effect does oestrogen have on GnRH?
A
Increased secretion.
23
Q
What kind of action is oestrogen driving an increase in GnRH?
A
Endocrine signalling.
24
Q
Can steroids pass through the cell membrane?
A
Yes - they are hydrophobic lipids.
25
Where are the **steroid receptors** found?
Cytoplasm or nucleus.
26
What is the function of a **chaperone** protein?
**Prevent** synthesised polypeptide chains and assembled subunits from **aggregating.**
27
Where in the cell are **oestrogen** **receptors** found?
Within the **nucleus.**
28
What kind of **receptor** is the **ER**?
**Ligand-activated** transcription factor.
29
What happens when the **ER** forms a **dimer**?
It binds **response elements** in target **gene promoters**.
30
What does the **ER regulate**?
* Protein levels - through **translation**.
* Position within the cell - through **translocation**.
31
Is **estradiol** found in men or women?
Both.
32
What is the **ER**?
Estrogen receptor.
33
What is **E2**?
Symbol for **oestradiol**.
34
What is **estradiol** (E2) ?
A major **estrogen** produced in the **ovaries** or via **aromatase pathway.**
35
What are the **6 biological roles** of **E2**?
* Fertility.
* **Lordosis** behaviour - sexual responsiveness.
* Neurogenesis - maintaining brain function.
* Cardiovascular.
* Bone strengthening.
* Reduces incidence of some tumours.
36
What effects does **E2** have in **bone**?
* **Stimulates growth hormone** secretion - this regulates bone growth.
* Promotes bone **formation** (rather than resorption) - by reducing osteoblast and osteoclast production.
37
What effects does **E2** have on the **cardiovascular** system?
* Regulates **nitric oxide.**
* Increases coronary flow.
* Increases cardiac output.
* Reduces fats in the blood.
38
What is **cardiac output**?
The **amount** of blood the heart pumps through the circulatory system in a **minute.**
39
What is **coronary flow**?
Movement of blood through the **vessels** of the heart, specifically from the ascending **aorta**.
40
How can **cardiac** risk (heart disease) due to menopause be treated?
Hormone replacement therapy.
41
What is **P450 aromatase**?
**Enzyme** required for the **biosynthesis of estrogen**.
42
What is **cytochrome P450**?
A **group of enzymes** required for **steroidogenesi**s.
43
How can breast cancers be **treated**?
**Inhibiting** P450 aromatase expression - inhibits the production of estrogens.
44
What is **VEGF**?
**Signal protein** that stimulates vasculogenesis and angiogenesis.
45
What does **VEGF** stand for?
Vascular endothelial growth factor.
46
What is **angiogenesis**?
Developing new blood vessels.
47
What are the different kinds of **angiogenesis**?
* Sprouting.
* Intussusceptive/splitting.
48
When does **angiogenesis** occur?
* Wound-healing.
* Monthly cycle (females).
* Building of the placenta.
49
What **differences** can be observed between the **VEGF isoforms**?
Different **isoelectric** points - acidic ranges.
50
What is a **homodimer**?
A molecule composed of paired **identical** proteins.
51
How is **VEGF** made biologically **active**?
**Proteolytic** cleavage by proteases.
52
Why do tumours **generate** **proteases**?
So that they **activate more VEGF** and so that more **angiogenesis** takes place.
53
What factors **increase VEGF** expression?
* **Hypoxia** (low O2).
* Myocardial **ischaemia**.
* **Cytokines** and **growth factors**.
* Cell **differentiation**.
* **Tumour** induction.
* **Oncogenes**.
54
What **oncogenes** mediate **VEGF expression**?
**ras** and **raf**.
55
What **hormone** leads to more expression of **VEGF** in **granulosa cells**?
**Luteinising** hormone.
56
What kind of **receptors** does **VEGF** bind to?
Receptor tyrosine kinase.
57
What is an **SH2 domain**?
Src homology 2 - **sequence-specific phosphotyrosine-binding module** present in many signaling molecules allow **autophosphorylation**.
58
Outline signalling initiation of **receptor tyrozine kinases**?
1. **Ligands bind** to the receptor - **stable dimers** are formed.
2. Receptor **activation** occurs - **autophosphorylatio**n is stimulated.
3. **Signalling complex formed** - intracellular proteins containing SH2 regions bind to phosphotyrosin.
59
What is **autophosphorylation**?
Process in which a **phosphate is added** to a protein kinase.
60
What kind of **molecules** have **SH2 domains**?
Intracellular proteins.
61
Even though **SH2 domains** may bind the **same receptor** tyrozine kinase, can they **activate different pathways**?
Yes.
62
What happens to mice **heterozygous** for **VEGF**?
die in utero.
63
What effect does **removing VEGF** have?
Increased **mortality** and **stunted** body growth.
64
What effect does **VEGF** have on **hepatic cells**?
Protects them from apoptosis and causes **proliferation**.
65
What is **vasculogenesis**?
Formation of the vascular (blood) network in the **embryo**.
66
What effect does **VEGF** have on the **kidney**?
It regulates the **function in the glomerulus** - removal results in renal disease.
67
What effect does **VEGF** have on **bone formation**?
Promotes **longitudinal bone growth.**
68
What role does **VEGF** play in **endocrin glands**?
Regulates **follicular development** and **corpus luteum** generation.
69
What type of **cancers** secrete a lot of **VEGF**?
**Carcinomas** - malignant cancers.
70
What **other conditions** (not cancer) show an increase in **VEGF** expression?
* Eye disorder.
* Inflammatory disorders.
* Endometriosis + PCOS.
71
What **treatments** are applied to patients with disorders associated with high **VEGF**?
* Anti-VEGF monoclonal antibodies.
* Co-treatment with chemotherapy.
72
What does low levels of **VEGF** in **spinal cord neurons** lead to?
Sclerosis.
