Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endo/Repro Midterm > Hormone Signaling Pathways > Flashcards

Hormone Signaling Pathways Flashcards

1
Q

Hormones are messenger molecules synthesized and secreted by _______ cells. They are released into ______ or the blood stream and exert their influence by binding receptors on cells of remote target tissues

A

Endocrine

ECF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Hormones binding their receptors results in activation of signal ______ and/or alteration in ______ expression ultimately leading to cell type-specific response

Only a small amount is required to alter cell metabolism because the effect is greatly magnified via signal ________

A

Transduction; gene

Amplification

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Multistep process of hormone signaling

A 
Biosynthesis
Storage
Secretion
Transport to target tissue/cells
Recognition and binding to receptors
Activation of signal transduction pathway
Amplification and relay of signal
Cellular response
Degradation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

4 types of cell signaling

A

Endocrine
Paracrine
Autocrine
Juxtacrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

___________ signaling = signaling molecule released by a cell distant from target cell and transported via blood to target cell

A

Endocrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

___________ signaling = signaling molecule acts on same cell type as secreting cell itself (ex. IL-1)

A

Autocrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

___________ signaling = signaling molecule released by one cell type and diffuses to neighboring target cell of a different type

A

Paracrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

___________ signaling = signaling molecule stays attached to secreting cell and binds receptor on adjacent target cell via connexons (ex. Heparin-binding epidermal growth factor)

A

Juxtacrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

T/f: some signaling molecules participate in more than one type of signaling

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which of the following is typical of testosterone?

A. Endocrine signaling
B. Paracrine signaling
C. Autocrine signaling
D. Juxtacrine signaling

A

B. Paracrine signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which of the following is typical of epinephrine?

A. Endocrine signaling
B. Paracrine signaling
C. Autocrine signaling
D. Juxtacrine signaling

A

A. Endocrine signaling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Which of the following are hydrophilic hormones?

A. Epinephrine
B. Insulin
C. Steroid hormones
D. Glucagon
E. Thyroid hormone
F. Retinoids
A

A. Epinephrine
B. Insulin
D. Glucagon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which of the following are lipophilic hormones?

A. Epinephrine
B. Insulin
C. Steroid hormones
D. Glucagon
E. Thyroid hormone
F. Retinoids
A

C. Steroid hormones
E. Thyroid hormones
F. Retinoids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What types of receptors are involved in hydrophilic hormone signaling?

A

GPCRs

RTKs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Lipophilic hormones pass through the plasma membrane of the target cell and bind to either ______ receptors or ______ receptors, either way regulating the transcription of specific genes

A

Cytoplasmic

Nuclear

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe lipophilic hormone signaling via cytoplasmic receptors

A

They exist in an inactive complex with HSP90. Upon binding to signal, the HSP dissociates

The hormone receptor complex translocates to nucleus where it binds to a specific DNA sequence called the hormone response element (HRE) in the promoter region of specific genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe lipophilic hormone signaling via nuclear receptors

A

They are already present in the nucleus bound to DNA. The hormone signal activates the complex and allows for interactions with additional proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Epinephrine is a ______ signal that binds a _______ to cause cellular response

A

Hydrophilic; GPCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Insulin is a ______ signal that binds a _______ to cause cellular response

A

Hydrophilic; RTK

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the difference between lipophilic and hydrophilic medications?

A

Hydrophilic have SHORT half lives (e.g. epinephrine); given at time of need

Lipophilic have long half lives (e.g. oral contraceptives); taken daily

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

GPCR signaling occurs via trimeric G proteins containing 3 subunits (_____, _____, ____)

An inactive G protein has GDP bound to its _____ subunit, which is attached to the other 2 subunits.

To become active, the G protein must exchange its GDP for a GTP, this occurs via the action of _______

The active GTP-bound ____ subunit separates from the other 2 to potentiate activation signal

A

Alpha, beta, gamma

Alpha

GEF (guanine nucleotide exchange factor)

Alpha

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

For a GPCR to return to its inactive state, the intrinsic GTPase activity of the G protein hydrolyzes its bound GTP to GDP and Pi

This action is accelerated by a ______

A

GAP (GTPase-activating protein)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Describe 4 different GPCR signaling variations: Gs, Gt, Gi, Gq

A

Gs = stimulates adenylate cyclase, forms cAMP, activates PKA, phosphorylates targets

Gt = stimulates hydrolysis of cGMP by phosphodiesterase

Gi = inhibits adenylate cyclase

Gq = stimulates PLC —> DAG and IP3 —> PKC and calcium/calmodulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Epinephrine binds beta-adrenergic GPCR, activating _____ subunit

What is the physiologic response?

A

Gs

Relaxation of bronchial and intestinal smooth muscle, contraction of heart muscle, increased breakdown of TAGs in adipose tissue, increased breakdown of glycogen in liver and muscle, increased glycolysis in muscle

[epinephrine is a non-selective agonist of all adrenergic receptors and results in multpile GPCR signaling pathways]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Histamine binds ______ GPCR, activating _____ subunit

What is the physiologic response?

A

Histamine H2; Gs

Bronchoconstriction and symptoms of allergic reaction (e.g. itchy, watery eyes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Epinephrine/Norepinephrine binds alpha-adrenergic GPCR, activating _____ subunit

What is the physiologic response?

A

Gi

Constriction of smooth muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Dopamine binds ______ GPCR, activating _____ subunit

What is the physiologic response?

A

Dopamine D2; Gi

Increased heart rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Acetylcholine binds ______ GPCR, activating _____ subunit

What is the physiologic response?

A

Muscarinic ACh M3; Gq

Bronchoconstriction and stimulation of salivary glands

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Light binds ______ GPCR, activating _____ subunit

What is the physiologic response?

A

Rhodopsin; Gt

Vision

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

RTKs have an extracellular domain that binds the ligand/signaling molecule, a single ________ transmembrane domain, and an intracellular domain with _____ activity

A

Alpha-helical; tyrosine-kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Typical ligands of RTKs are growth factors. What is the result of ligand binding to RTK extracellular domain?

A

Dimerization

The dimerized receptor then phosphorylates tyrosine residues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Dimerized RTKs phosphorylate tyrosine residues. What effect does this have on signaling process?

A

Phosphotyrosines are recognized by adaptor and docking proteins which activate downstream signaling pathways (RAS dependent and RAS independent) - both of which trigger phosphorylation of specific protein targets in cytoplasm/nucleus leading to alterations in gene transcription and protein activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Are MAPK pathway signals RAS-dependent or RAS-independent?

A

RAS-dependent

[RAS-independent include other kinases]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

How is RTK signaling terminated?

A

Multiple mechanisms: degradation of ligand by EC proteases, ligand-induced endocytosis of receptor and its degradation, RAS inactivation, dephosphorylation of protein targets by phosphatases

35
Q

Primary structure of insulin

A

2 peptide chains: A chain and B chain, linked together by 2 disulfide bridges, and an additional disulfide is formed within the A chain

36
Q

In most species the A chain of insulin consists of ____ amino acids and the B chain of ____ amino acids

A

21; 30

37
Q

The secondary and tertiary structure of insulin involves 6 insulin molecules assembled in a ______ with 3-fold symmetry with _____ in the center, connected to the polypeptide via ________

A

Hexamer; zinc; histidines

38
Q

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

A

Hexamer; monomer

39
Q

Insulin synthesis and secretion:

Glucose upregulates ______ mRNA, which is translated into ______ protein. This gets translocated into _____ lumen

A

Preproinsulin; preproinsulin; ER

40
Q

Describe insulin synthesis and secretion once the preproinsulin protein has been translocated to the ER lumen

A

It is cleaved by a protease to form proinsulin, folded and transported to golgi, packaged into clathrin coated granules, cleaved by proteases to form insulin and C peptide, forms mature granules containing hexameric crystallized insulin (3dimers), insulin + C peptide released together by beta cells of pancreas

41
Q

After glucose stimulation, insulin is released in what 2 distinct phases?

A

First phase = rapid but transient; comes from limited pool of granules referred to as readily releasable pool (RRP) - <5%

Second phase = sustained; comes from larger pool referred to as reserve pool. Granules in this pool must undergo mobilization before they can gain release competence - >95%

42
Q

Regulation of insulin synthesis and secretion:

Glucose binds ______ receptor, resulting in _______ enzyme forming G1P

Insulin granules are released by opening of ______ channels in cell membrane, as well as closing of ATP-sensitive _____ channels when energy in cell increases

A

GLUT2; glucokinase

Ca++; K+

43
Q

Describe Ras-dependent insulin signaling

A

Insulin binds to RTK which exists as preformed dimer, causing autophosphorylation of tyrosine residues

Phosphotyrosine residues are recognized and bound by IRS-1, which is phosphorylated on its tyrosine by insulin receptor

Phosphorylated IRS-1 is recognized and bound by adaptor protein GRB-2, initiating activation of Ras and Map kinase pathway

Results in phosphorylation of nuclear proteins that increase transcription of glucokinase

Glucokinase phosphorylates glucose in the first step of glycolysis and glycogen synthesis

44
Q

Describe Ras-independent insulin signaling

A

Insulin binds RTK which exists as a preformed dimer, causing autophosphorylation of the tyrosin residues

Phosphotyrosine residues recognized and bound by IRS-1

IRS-1 phosphorylated on its tyrosin by insulin receptor

Phosphorylated IRS-1 recruits PI3kinase, which phosphorylates phosphoinositides to form PIP3

PIP3 act as second messengers, stimulating recruitment of PKB to the membrane and its activation by phosphorylation

Active PKB (serine threonine kinase aka Akt) phosphorylates and alters IC proteins to stimulate glucose uptake and storage (upregulates GLUT4, inhibits glycogen synthase kinase via phosphorylation)

45
Q

What quantifiable lab parameter is measured as the amount of glucose cleared from the blood in response to a fixed dose of insulin?

A

Insulin resistance

46
Q

What types of conditions might lead to insulin resistance?

A

Defects in insulin signaling (receptor activation to translocation of GLUT4)

Mutations in insulin receptor

Increased phosphorylation of serine (via ser/thr kinase) instead of tyrosine in IR and IRS - inhibits activation and signaling

47
Q

Insulin resistance may result d/t increased phosphorylation of serine via ser/thr kinase instead of tyrosine in the IR and IRS - which inhibits activation and signaling

Phosphorylation of IRS is needed for recruitment of PI3 kinase but ser/thr phosphorylation appears to inactivate the IRS 1 and 2, leading to degradation

What activates the Ser/Thr kinase to cause this effect?

A 
Cytokines
Free fatty acids
DAG
Ceramide
Inflammatory molecules
48
Q

What hormone is released from the pancreas under conditions of hunger

A

Glucagon

49
Q

How does glucagon increase blood sugar

A

Promoting breakdown of glycogen in liver and inhibiting glycogen synthesis

50
Q

How does epinephrine affect glycogen breakdown

A

Stimulates it by promoting glucagon secretion

51
Q

Upon depletion of glycogen stores, the steroid hormone _____ stimulates gluconeogenesis by inducing transcription of enzymes involved in this path

A

Cortisol

52
Q

Nuclear receptors are a large family of receptors classified based on ligands they bind. What are the 3 general classifications?

A

Classic NRs - ligands are lipophilic hormones like glucocorticoids, mineralocorticoids, estrogen, progesterone, androgens

Orphan NRs - other group of receptors discovered by DNA sequencing (ligands unknown)

Adopted NRs - orphan NRs whose ligands have been discovered like retinoids, thyroid hormones, vitamin D, xenobiotics, androstane, etc.

53
Q

NRs may be localized in what 2 locations

A

Nucleus

Cytosol

54
Q

What are some diseases involving abberrations in NR signaling?

A 
Reproductive disorders
Cancer
Diabetes
Inflammation
Cardiovascular disorders
Obesity
55
Q

NRs share the same architecture

What are the 3 major domains?

A

Activation 1 domain (AF1)

DNA binding domain (DBD)

Ligand binding domain (LBD)

56
Q

Describe the activation function 1 domain (AF1) of NRs

A

Independent of ligand binding, can modify the conformation of entire receptor

57
Q

Describe the DND binding domain (DBD) of NRs

A

Highly conserved; binds regulatory sequences on DNA called hormone response element (HRE), upstream of target gene

58
Q

Describe Ligand Binding domain (LBD) of NRs

A

Binds various molecules (agonist or antagonist) which regulates ligand-dependent activation of the receptor

Upon ligand binding within LBD, conformational changes occur allowing recruitment and binding of coactivators or corepressors that regulate transcription

59
Q

T/F: NRs exist as homo or heterodimers

A

True

60
Q

2 major types of estrogen receptor

A

ER-alpha

ER-beta

61
Q

The 2 major types of estrogen receptors, ER-alpha and beta, are products of 2 separate genes located on different chromosomes

Their structure is the almost the same with some differences. Both are estrogen-dependent ________ ________

A

Transcription factors

62
Q

ER-alpha was the first estrogen receptor discovered. Where is it most abundantly expressed?

A

Female reproductive tract (uterus, vagina, ovaries)

Mammary gland, hypothalamus, endothelial cells, vascular smooth muscle

63
Q

Where is ER-beta most abundantly expressed?

A

Prostate and ovaries

Lower expression in lung, brain, bone, vasculature

64
Q

T/F:

Many cells express both ER-alpha and beta

They dimerize to form either homo or heterodimers, and the final biological effect is mediated by the ratio of the 2 forms

A

True

65
Q

Both ER-alpha and beta are expressed in breast cancers, although _____ is believed to be the predominant form responsible for growth regulation

A

ER-alpha

66
Q

Estrogen acts as an _______ at the ER, upregulating ______activity and ______ transcription

A

Agonist
HAT
Activating

67
Q

Tamoxifen acts as an _______ at the ER. It is first converted to 4-hydroxy-tamoxifen via _______ metabolism, which then upregulates _____ activity and ______ transcription

A

Antagonist
CytP450
HDAC
Inhibist

68
Q

Molecular MOA of nuclear estrogen receptor:

ER exists as a _____ within the nucleus

The ligand binds the receptor, causing conformational change facilitating _________ with specific estrogen response element sequences in DNA

The ER-DNA complex recruits _______ that modify chromatin structure and SRC-1, which further alters chromatin structure by virtue of its _______ activity

Chromatin remodeling facilitates binding of other coactivators to promoter of target genes and recruit proteins that comprise the general _______ apparatus, leading to enhanced transcription to form mRNA

A

Monomer

Dimerization

Co-activators; HAT

Transcription

69
Q

T/F; Although it is thought that ER exists as a monomer within the nucleus, some evidence suggests it can be located in the cytosol and estrogen binding causes dimerization and translocation to the nucleus

A

True

70
Q

Antagonists like tamoxifen recruit HDACs which act on histone proteins to stabilize nucleosome structure; how do things like tamoxifen prevent transcription?

A

By stabilizing the nucleosome structure, they prevent interaction with the general transcription apparatus and prevent transcription

71
Q

Some ERs are considered non-genomic, where are their receptors located and what type of receptors are they?

A

Some in PM

Some in caveolae (cholesterol enriched domains in PM)

There are GPCR and RTK type non-genomic ERs

72
Q

How are non-genomic ER effects mediated?

A

Through metabolic changes as well as changes in gene expression

73
Q

Production of gonadal hormones testosterone and estrogen are under the control of the ______ and _______

A

Hypothalamus; anterior pituitary

74
Q

Cortisol, aldosterone, and androgens are steroid hormones synthesized in the ________

A

Adrenal cortex

75
Q

Estrogens and progesterone are steroid hormones synthesized in _____

A

Ovaries

76
Q

What steroid hormone is synthesized in the placenta?

A

Progesterone

77
Q

Is histamine lipophilic or hydrophilic? What type of receptor does it bind?

A

Hydrophilic

Binds GPCR

78
Q

Differentiate type I vs. type II nuclear receptors

A

Type I - reside in cytoplasm with ligand-mediated translocation to the nucleus

Type II - reside in nucleus to mediate active repression of gene expression until hormone binding comes in to change the response

79
Q

Estrogen receptors bind to core inverted repeat DNA sequences using 2 _________ that are ________

A

Zinc-fingers; palindromes

80
Q

What happens to the co-activators or co-repressors when a hormone comes along to change the gene expression?

A

They are degraded in proteosome after being ubiquitinated

81
Q

4 types of reversible post translational modifications on nuclear receptors

A

Phosphorylation
Acetylation
Ubiquitination
Sumoylation

82
Q

Ubiquitination, sumoylation, and acetylation typically compete for ______ residues on NRs

A

Lysine (K)

83
Q

Phosphorylation is a PTM that typically occurs at _____ residues on NRs

A

S/T

Endo/Repro Midterm (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions