Mech of Hormone 174

Question 1

What are common features of ligands for nuclear receptors?

Answer 1

small

lipophilic

synthesized by enzymes from precursors or sourced exogenously (i.e. not encoded by genome)

Question 2

How are nuclear receptors classified?

Answer 2

classified by ligand type

i.e. hormones, vitamins, metabolites

Question 3

What is the hormone response element of nuclear receptors?

Answer 3

a region of DNA that is specific to a particular receptor

often close to the promotor of genes regulated by the particular receptor

Question 4

How are nuclear receptors regulated?

Answer 4

can be regulated on the ligand level (availability, synthesis, secretion, activation, clearance) or on the receptor level (whether or not a cell expresses a receptor)

also related to coactivators and corepressors

Question 5

What are the consequences of nuclear receptor activation?

Answer 5

regulates gene transcription

can either upregulate it or downregulate it

Question 6

What type of receptor is dysfunctional in the following diseases: THRB resistance, complete androgen insensitivity syndrome, hereditary vitamin D resistance.

Answer 6

nuclear receptor disorders

thyroid hormone, androgens, and vitamin D all signal to nuclear receptors

Question 7

What are the six major classes of membrane receptors?

Question 8

What are the components (3) of receptor tyrosine kinases?

Answer 8

1) extracellular ligand binding domain
2) single transmembrane domain
3) intracellular tyrosine kinase catalytic domain

Question 9

What structural changes occur to receptor tyrosine kinases after ligand binding?

Answer 9

they dimerize

sometimes they also autophosphorylate (ex. insulin)

Question 10

What is the function of receptor serine/threonine kinases?

Answer 10

a dimerizing membrane receptor that phosphorylates serine and threonine

Question 11

What is the general pathway of cytokine activated receptors?

Answer 11

a membrane receptor that is activated by cytokines and acts on associated tyrosine kinases (JAK/STAT pathway)

Question 12

What are major cytokine activated receptors?

Answer 12

growth hormone (needed for growth)

prolactin (needed for reproduction/lactation)

leptin (suppresses appetite, regulates metabolism)

Question 13

What is the structure of GPCRs?

Answer 13

7 transmembrane-spanning helices with associated G-protiens (alpha, beta, and gamma subunits)

Question 14

What is the classical pathway of G proteins?

Answer 14

Gs and Gi stimulate and inhibit (respectively) cAMP production by adenylate cyclase

Question 15

What is the non-classical pathway of G proteins?

Answer 15

Gq protein induces phospholipase C mediated cleavage of PIP2 to IP3 and DAG, which both contribute to downstream signaling

Question 16

How can GPCR signaling be fine-tuned?

Answer 16

they can be endocytosed to remove them from the membrane or phosphorylated to desensitize them

Question 17

What type of membrane receptor is disordered in nephrogenic diabetes insipidus?

Answer 17

GPCR malfunction

failure to incorporate aquaporin GPCRs into the membrane to concentrate urine

Question 18

What is the general pathogenesis of Graves disease?

Answer 18

activating antibodies bind to the TSH receptor (a GPCR), leading to hyperthyroidism

Question 19

Graves’ thyroid disease is a result of one of the following:

a) nuclear receptor gain of function mutations
b) activating antibodies to thyroid hormone receptors
c) stimulating antibodies to the TSH receptor
d) a somatic activating mutation to the TSH receptor

Answer 19

c) stimulating antibodies to the TSH receptor

a gain of function mutation to a GPCR

Question 20

Nuclear receptors are activated by ligands that:

a) are peptides and large proteins
b) are small molecules derived from the human genome
c) water soluble ligands derived from amino acids
d) lipophilic compounds molecules that are not directly derived from the genomic sequence

Answer 20

d) lipophilic compounds molecules that are not directly derived from the genomic sequence

Question 21

To what class of receptors does the insulin receptor belong?

a) nuclear receptor
b) tyrosine kinase
c) GPCR

Answer 21

b) tyrosine kinase