2-1-16-Hormone Signaling Pathways (Zaidi)

Question 1

What type of receptors are involved in hydrophilic hormone signaling?

Answer 1

GPCRs

RTKs

Question 2

Regarding cytoplasmic receptors, the hormone-receptor complex translocates to the nucleus where it binds to specific DNA sequence called the ___ in the promoter region of specific genes

Answer 2

Hormone Response ELement

Question 3

Steroid hormones are ___ molecules

Epinephrine and insulin are ___ molecules

Use either hydrophobic or hydrophilic

Answer 3

Hydrophobic

Hydrophilic

Question 4

___ medications have short 1/2 lives, i.e., epinephrine is contained in autoinjectors used to treat severe acute allergic rxns that may lead to anaphylactic shock. Given at time of need

___ meds have long 1/2 lives, i.e., oral contraceptives contain ethinyl estradiol, a derivative of estradiol. Need to take daily

Answer 4

Hydrophilic

Lipophilic

Question 5

An inactive G protein has GDP bound to its alpha subunit, which is attached to the beta and gamma subunits. To become active, the G protein must exchange its GDP for GTP which occurs via the action of a ____

Answer 5

Guanine nucleotide exchange factor (GEF)

Question 6

To return active GTP to its inactive GDP, the intrinsic GTPase activity of the protein hydrolyzes its bound GTP to GDP and Pi and is accelerated by ____

Answer 6

GTPase-activating protein (GAP)

Question 7

___ stimulates AC

___ inhibits AC

___ stimulates hydrolysis of cGMP

Answer 7

Gs

Gi

Gt

Question 8

GPCR signaling via Gq leads to downstream activation of:

Answer 8

GTP-alpha activating PLC –> PIP 2 —> IP3 and DAG –> IP3 binds Ca channels and releases sequestered ER/SR Ca which then can bind with calmodulin and activate Ca-calmodulin dependent proteins or activate PKC which phosphorylates target proteins to alter their activities –> DAG can activate PKC directly

Question 9

What are the effects of Epi binding to Gs protein and B-adrenergic receptor?

Answer 9

Relaxation of bronchial and intestinal smooth m., contraction of heart muscle, increased breakdown of TAGs in adipose, increase breakdwon of glycogen in liver and muscle, increased glycolysis in muscle.

Epi is a non-selective agonist of all adrenergic receptors and undergoes multipled GPCR signaling pathways

Question 10

What are the effects of histamine binding to a Gs histamine H2 receptor?

Answer 10

Bronchoconstriction and symptoms of allergic rxns

Question 11

What are effects of epi/norepi binding to a Gi alpha-adrenergic receptor?

Answer 11

constriction of smooth m.

Question 12

Inactive insulin is stored in the body as a ___, while the active form is the ___

Insulin has a 3-fold symmetry with ___ in the center connected to the polypeptide via histidines

Answer 12

Hexamer

Monomer

Zinc

Question 13

Insulin signaling occurs through ___

Answer 13

Ras-dependent and indepent Receptor Tyrosine Kinase

Question 14

Describe insulin signaling through Ras-dependent pathway

Answer 14

Insulin bind insulin RTK –> IRS-1 binds GRB-2 –> Ras –> Phosphorylated protein –> Alteration in gene transcription, e.g., increased transcription of glucokinase –> increase glucose uptake and/or glycogen synthesis

Question 15

Describe insulin signaling through RAS-independent pathway:

Answer 15

Insulin binds insulin RTK –> IRS-1 binds PI-3 kinase –> PKB –> Phosphorylated protein –> alterations in protein and enzyme activity e.g., increased GLUT4 movement to plasma membrane; activation of glycogen synthase –> increase glucose uptake and/or glycogen synthesis

Question 16

Under ___ conditions, insulin lowers blood glucose by promoting glycogen synthesis, stimulating glycolysis, and inhibiting the activity and synthesis of enzymes for gluconeogenesis

Answer 16

Fed

Question 17

List classic steroid nuclear receptors:

Answer 17

The ligands are lipophilic hormones

Glucocorticoids (GR)
Mineralocorticoids (MR)
Estrogen (ER)
Progesterone (PR)
Androgens (AR)

Question 18

List orphan receptors/their ligands:

Answer 18

Retinoids
Thyroid
Vitamin D
Xenobiotics
Androstane

Question 19

What are the 3 major domains of nuclear receptors?

Answer 19

AF1
DBD
LBD

Question 20

___ domain is independent of ligand binding, can modify the conformation of the entire receptor

Answer 20

AF1 (Activation Function 1 domain)

Question 21

___ domain is highly conserved, binds to regulatory sequences on DNA called HRE, upstream of target gene

Answer 21

DBD (DNA binding domain)

Question 22

___ domain binds to various molecules (agonist or antagonist) which regulates ligand-dependent activation of receptor. Upon ligand binding a region within this domain, it undergoes conformational changes allowing recruitment and binding of coactivators or corepressors that regulate transcription

Answer 22

LBD (ligand binding domain)

Question 23

___ is expressed most abundantly in the female reproductive tract (especially in the uterus, vagina, and ovaries). Also in the mammary gland, hypothalamus, endothelial cells, and vascular smooth m.

Answer 23

ER-alpha

Question 24

___ is expressed most abundantly in the prostate and ovaries, with lower expression in lung, brain, bone, and vasculature

Answer 24

ER-beta

Question 25

Both ERalpha and beta are expressed in ___, although ERalpha is believed to be the predominant form responsible for growth regulation

Answer 25

Breast cancers

Question 26

One of the critical aspects of insulin resistance leading to diabetes is a loss of insulin stimulation of glucose uptake by ___ in adipose and skeletal muscle.

Answer 26

GLUT4

Question 27

When glucose deficiency occurs (starved), the pancreas releases the peptide hormone ____. Similarly, ___ stimulates the breakdown of glycogen by promoting glucagon secretion. If the glycogen stores have been depleted, then the steroid hormone ___ stimulates gluconeogenesis by inducing transcription of enzymes involved in glucose-producing pathway.

Answer 27

Glucagon

Epinephrine

Cortisol

Question 28

List examples of hydrophilic hormones:

Answer 28

Epi, insulin, glucagon

Question 29

____ is an drug that acts as an antagonist to estrogen and binds to Estrogen receptor but produces a different receptor conformation

Answer 29

Tamoxifen –> different set of proteins called co-repressors, such as NcoR, are recruited to the complex. NcoR further recruits proteins such as HDAC1 that act on histone proteins to stabilize the nucleosome structure and prevent interaction with the GTA