Hormone Signalling Pathways

Question 1

What are the two types of Nuclear Receptors?

Answer 1

1) Classic Nuclear Receptors: Bind lipophillic hormones
2) Orphan Receptors: Ligand Unknown (Know receptors are called “Adopted” Receptors

Question 2

Where are nuclear receptors located?

Answer 2

They are located in either the nucleus or the cytosol

Question 3

What are the three major domains for nuclear receptors (NRs)?

Answer 3

1) AF1 (Activation Function 1 Domain)
2) DNA Binding Domain (DBD)
3) Ligand Binding Domain (LBD)

{ADL: Always Down Low}

Question 4

What is the function of AF1 in nuclear receptors?

Answer 4

1) AF1 (Activation Function 1 Domain) –> Independent of ligand binding, and can modify the conformation of the entire receptor

Question 5

What is the function of DBDs in nuclear receptors

Answer 5

1) DNA Binding Domains (DBDs) –> Bind to regulatory sequences on DNA; called hormone response elements (HREs)

Question 6

What is the function of LBDs in nuclear receptors?

Answer 6

1) LBDs (Ligand Binding Domains)

–> They bind to various molecules (agonist or antagonist) which regulates ligand-dependent activation of a receptor.

–> Upon ligand binding a region within the LBD will undergo conformational change allowing the recruitment and binding of coactivators or corepressors that regulate transcription

Question 7

Describe the basic process of a receptor & steroid hormone complex inducing the production of gene transcription and protein product formation

Answer 7

1) Steroid Hormone & Receptor –> activate primary response genes –> produce primary response proteins
2) Primary reponse proteins –> Inhibit primary reponse gene activaition

2B) Primary response proteins activate secondary response genes –> produce secondary response proteins

Question 8

What are the two forms of Estrogen receptors expressed in breast cancer?

What is the primary form responsible for growth regulation?

Answer 8

1) ER(Alpha) & ER(Beta)
2) ErA: responsible for growth

Question 9

ERA (Estrogen Receptor Alpha); Is mostly expressed where in the body?

Answer 9

Along the female reproductive tract; Uterus, Vagina, & Ovaries (UVO*)

Also found in the mammary gland, Hypothalamus, Endothelial cells, and Vascular smooth muscle

Question 10

ERB (Estrogen Receptor Beta) is mostly found where in the body?

Answer 10

ALong the prostate and ovaries

Lower expression in the lung, brain, bone, and vasculature

Question 11

What is the cellular mechanism of action of Estrogen when it binds to its’ receptor?

Answer 11

1) Estogen binds –> Activates HAT (Histone Acetyltransferase) –> Makes chromatin less compact –> Increases transcription of genes
2) Also, recruits proteins that comprise the GTA (General transcription apparatus)

Question 12

What is the cellular mechanism of action of Tamoxifen when it binds to its receptor?

Include what Tamoxifen is broken down into and via what enzyme this process occurs

Answer 12

1) Tamoxifen is an antagonist of Estrogen; –> recruits NcoR (Nuclear hormone co repressor) –> recruits HDAC1 (Histone Deacetylase 1) to keep chromatin compact and inhibit transcription {prevents interaction with the GTA}
2) Tamoxifen is broken down via Cytrochrome P450 –> 4-hydroxy-tamoxifen

Question 13

Where is the Estrogen Receptor located and what occurs with the binding of Estrogen to the receptor?

Answer 13

1) Estrogen Receptor is located in the Cytosol
2) Binding of Estrogen to the receptor causes it to translocated to the Nucleus

Question 14

When was the crystal structure of insulin solved?

Also, inactive insulin is stored in the body in what form; (include the center metal ion & connection to polypeptides)

Answer 14

1) 1926
2) Insulin is stored in the inactive form via a hexamer; surrounding Zinc, and connected to polypeptides via histidines

Question 15

What are the two forms of Lipophillic Hormone Signalling Receptors?

Answer 15

1) Cytoplasmic receptors
2) Nuclear Receptors

Question 16

Describe the basic process upon binding of a steroid hormone to a cytoplasmic receptor

Answer 16

1) Hormone binds to the cytoplasmic receptor (which is usually in an inactive form complexed w/ HSP 90)
2) Upon binding; the complex translocates to the nucleus to bind to a specific DNA sequence, called the hormone response element (HRE)

Question 17

Catechomalines fall under what classification of hormones (lipophillic or hydrophillic)?

Answer 17

1) Hydrophillic

Question 18

What is the basic process involving the Gs pathway?

Answer 18

Gs –> Adenylate Cyclase –> cAMP –> PKA –> PHosphorylates targets

Question 19

What is the basic process involving the Gt pathway?

Answer 19

Gt –> hydrolysis of cGMP via phosphodiesterase