SYSTEMS BIOLOGY EXAM 4
QUESTIONS WITH COMPLETE
SOLUTIONS
Steroid Receptors - ANSWER-highly conserved, composed of amino-acid terminal
domain, DNA-binding domain, hinge region, and carboxy-terminal ligand binding
domain
Hormone response elements (HRE) - ANSWER-present in promoter region and
makes gene responsive to a particular hormone. Enhancers and nuclear receptors
that bind to them serve as transcription factors, each receptor has specific hexameric
motif to which it binds. most nuclear receptors bind as dimers so hexameric motif is
repeated twice to form HRE
Coregulators - ANSWER-modulate transcriptional effects of steroid receptors,
different in different cells types allowing for different hormone responses
Claude Bernard - ANSWER-A french physiologist 1813-1878 that investigated the
glycogenic function of the liver and postulated that many organs have the ability
"internal secretion" not only endocrine, which would be required through
homeostasis
Understanding of Endocrine system today: - ANSWER-hormonal function is a
general biological function of many cells independent of development and primary
role
What characteristics define an endocrine gland or hormone - ANSWER-traditionally
defined as an organ whose primary purpose is to secrete hormones, which almost
every cell in the body can do, and some neurotransmitters can be considered
hormones
neurohormones - ANSWER-oxytocin, vasopresin
"New" endocrine glands - ANSWER-pineal gland (melatonin), heart, kidney, adipose
tissue, digestive tract
"Untraditional" Hormones - ANSWER-Skin-Vitamin D3
Liver-Calcitriol, IGF-1, angiotensinogen
Kidneys-calcitriol, erythropoietin
Stomach and small intestine-enteric hormones
Placenta-estrogen, progesterone, etc
Classic endocrine paradigms also challenged - ANSWER-1. many hormones can act
as autocrine, paracrine, or endocrine stimulation
2. Intra vs extracellular receptors-GCPRs can be intracellular
3. Parallel signaling pathways-ion channels direct activated or second messengers
4. Gene transcription can be activated by receptor or after GPCR activation
,Evidence for acute estrogenic effects - ANSWER-estrogen binds to a cell surface
receptor, introducing the possibility that estrogenic signaling may involve non-
transcriptional mechanism or indirect actions that influence gene expression.
Dependence of estradiol on GTP-binding has been demonstrated in endothelial
smooth muscle, neural, and cancer cells suggesting that estrogen can signal via
non-steroid receptor
Within minutes, sublingual estradiol decreases peripheral resistance in menopausal
women
In vessels, estradiol induces vasorelaxation in less than 5 minutes
Where is the GPCR estrogen receptor>? - ANSWER-may be on the plasma
membrane, shown by fluorescence GPCR found by RNA breast cancer, orphan
proteins, high ER negative or endoplasmic reticulum or the nucleus
Crosstalk between different signaling pathways - ANSWER-steroid hormone can
bind to nucleus and plasma receptors
both of which can lead to changes in gene expression and biological responses
Nuclear receptors response-hours to days
Plasma membrane receptor response- seconds or minutes
Local Estrogen Synthesis - ANSWER-1. most circulating estrogen is produced in
ovaries, but other tissues express the necessary components
2. while the relative amount produced locally is much lower because it is contained
with in a compartment tissue concentration can reach physiologically relevant levels
3. In postmenopausal women and men, where circulating estrogens are very low,
local production may play a more significant role
4. Likely paracrine or intracrine
Local estrogen synthesis problems in diseases - ANSWER-gynecomastia: may be
related to aromatase overexpression in breast cancer
Post-menopausal breast cancer-E2 in breast tumor is 20X the circulating estrogen
Selective Estrogen Receptor Modulators (SERMs) - ANSWER-some drugs that
block the action of estrogen in certain tissues mimic the action of estrogen in other
tissues, these differences allow estrogen-like drugs to interact in different ways with
the estrogen receptors in different tissues
i.e. blocking estrogen from cell proliferation
An example of SERM selectivity - ANSWER-Tamoxifen acts as an antagonist in
breast and an agonist in the uterus
-the coactivator 1 is higher in uterus than breast, and therefore the drug is more
agonistic in uterus
, Raloxifene behaves an an antagonist in both tissues due to strongly recruiting co-
repressor proteins
Renin-Angiotensin System - ANSWER-
Nuclear renin-angiotensin system - ANSWER-nuclear AT1 receptors are functional,
and can espress other RAS components. Renal RAS is located on the nuclear
membrane
RAAS function - ANSWER-protects against blood loss and can cause hypertension
Endocrine hormones - ANSWER-distributed in blood and binds to target cells
Paracrine hormones - ANSWER-acts locally on cells close to the secretion point
Autocrine hormones - ANSWER-local hormones that are secreted and bind to the
same cell
Binding Globulins - ANSWER-proteins in the plasma that bind hormones
Why are binding globulins important? - ANSWER-When hormones are bound to
these binding globulins, they are not able to diffuse across the plasma membrane
Higher levels of binding globulin indicates less free hormone and dampened
hormone signaling
endocrine feedback system - ANSWER-Secretory activity of glands not under the
direct control of the hypothalamic-pituitary axis is controlled by feedback signals of
regulatory variable they control
Classes of hormones - ANSWER-Protein and peptide hormones, steroid hormones,
and tyrosine derivatives
Peptide and Protein Hormones - ANSWER-largest class of hormones
hydrophilic molecules that bind to cell surface receptors, travel easier in blood, and
have to bind to cell surface receptors
Peptide Hormone synthesis - ANSWER-synthesized as pre-prohormones in the
ribosomes and process to prohormones in the ER, packaged for secretory vesicles,
released in response to influx of Ca, hormone and products of post-translational
processing are released into extracellular space
Ex: insulin, growth hormones, angiotensin, glucagon
Steroid Hormones - ANSWER-derived from cholesterol and are synthesized in
adrenal cortex, gonads, and placenta
QUESTIONS WITH COMPLETE
SOLUTIONS
Steroid Receptors - ANSWER-highly conserved, composed of amino-acid terminal
domain, DNA-binding domain, hinge region, and carboxy-terminal ligand binding
domain
Hormone response elements (HRE) - ANSWER-present in promoter region and
makes gene responsive to a particular hormone. Enhancers and nuclear receptors
that bind to them serve as transcription factors, each receptor has specific hexameric
motif to which it binds. most nuclear receptors bind as dimers so hexameric motif is
repeated twice to form HRE
Coregulators - ANSWER-modulate transcriptional effects of steroid receptors,
different in different cells types allowing for different hormone responses
Claude Bernard - ANSWER-A french physiologist 1813-1878 that investigated the
glycogenic function of the liver and postulated that many organs have the ability
"internal secretion" not only endocrine, which would be required through
homeostasis
Understanding of Endocrine system today: - ANSWER-hormonal function is a
general biological function of many cells independent of development and primary
role
What characteristics define an endocrine gland or hormone - ANSWER-traditionally
defined as an organ whose primary purpose is to secrete hormones, which almost
every cell in the body can do, and some neurotransmitters can be considered
hormones
neurohormones - ANSWER-oxytocin, vasopresin
"New" endocrine glands - ANSWER-pineal gland (melatonin), heart, kidney, adipose
tissue, digestive tract
"Untraditional" Hormones - ANSWER-Skin-Vitamin D3
Liver-Calcitriol, IGF-1, angiotensinogen
Kidneys-calcitriol, erythropoietin
Stomach and small intestine-enteric hormones
Placenta-estrogen, progesterone, etc
Classic endocrine paradigms also challenged - ANSWER-1. many hormones can act
as autocrine, paracrine, or endocrine stimulation
2. Intra vs extracellular receptors-GCPRs can be intracellular
3. Parallel signaling pathways-ion channels direct activated or second messengers
4. Gene transcription can be activated by receptor or after GPCR activation
,Evidence for acute estrogenic effects - ANSWER-estrogen binds to a cell surface
receptor, introducing the possibility that estrogenic signaling may involve non-
transcriptional mechanism or indirect actions that influence gene expression.
Dependence of estradiol on GTP-binding has been demonstrated in endothelial
smooth muscle, neural, and cancer cells suggesting that estrogen can signal via
non-steroid receptor
Within minutes, sublingual estradiol decreases peripheral resistance in menopausal
women
In vessels, estradiol induces vasorelaxation in less than 5 minutes
Where is the GPCR estrogen receptor>? - ANSWER-may be on the plasma
membrane, shown by fluorescence GPCR found by RNA breast cancer, orphan
proteins, high ER negative or endoplasmic reticulum or the nucleus
Crosstalk between different signaling pathways - ANSWER-steroid hormone can
bind to nucleus and plasma receptors
both of which can lead to changes in gene expression and biological responses
Nuclear receptors response-hours to days
Plasma membrane receptor response- seconds or minutes
Local Estrogen Synthesis - ANSWER-1. most circulating estrogen is produced in
ovaries, but other tissues express the necessary components
2. while the relative amount produced locally is much lower because it is contained
with in a compartment tissue concentration can reach physiologically relevant levels
3. In postmenopausal women and men, where circulating estrogens are very low,
local production may play a more significant role
4. Likely paracrine or intracrine
Local estrogen synthesis problems in diseases - ANSWER-gynecomastia: may be
related to aromatase overexpression in breast cancer
Post-menopausal breast cancer-E2 in breast tumor is 20X the circulating estrogen
Selective Estrogen Receptor Modulators (SERMs) - ANSWER-some drugs that
block the action of estrogen in certain tissues mimic the action of estrogen in other
tissues, these differences allow estrogen-like drugs to interact in different ways with
the estrogen receptors in different tissues
i.e. blocking estrogen from cell proliferation
An example of SERM selectivity - ANSWER-Tamoxifen acts as an antagonist in
breast and an agonist in the uterus
-the coactivator 1 is higher in uterus than breast, and therefore the drug is more
agonistic in uterus
, Raloxifene behaves an an antagonist in both tissues due to strongly recruiting co-
repressor proteins
Renin-Angiotensin System - ANSWER-
Nuclear renin-angiotensin system - ANSWER-nuclear AT1 receptors are functional,
and can espress other RAS components. Renal RAS is located on the nuclear
membrane
RAAS function - ANSWER-protects against blood loss and can cause hypertension
Endocrine hormones - ANSWER-distributed in blood and binds to target cells
Paracrine hormones - ANSWER-acts locally on cells close to the secretion point
Autocrine hormones - ANSWER-local hormones that are secreted and bind to the
same cell
Binding Globulins - ANSWER-proteins in the plasma that bind hormones
Why are binding globulins important? - ANSWER-When hormones are bound to
these binding globulins, they are not able to diffuse across the plasma membrane
Higher levels of binding globulin indicates less free hormone and dampened
hormone signaling
endocrine feedback system - ANSWER-Secretory activity of glands not under the
direct control of the hypothalamic-pituitary axis is controlled by feedback signals of
regulatory variable they control
Classes of hormones - ANSWER-Protein and peptide hormones, steroid hormones,
and tyrosine derivatives
Peptide and Protein Hormones - ANSWER-largest class of hormones
hydrophilic molecules that bind to cell surface receptors, travel easier in blood, and
have to bind to cell surface receptors
Peptide Hormone synthesis - ANSWER-synthesized as pre-prohormones in the
ribosomes and process to prohormones in the ER, packaged for secretory vesicles,
released in response to influx of Ca, hormone and products of post-translational
processing are released into extracellular space
Ex: insulin, growth hormones, angiotensin, glucagon
Steroid Hormones - ANSWER-derived from cholesterol and are synthesized in
adrenal cortex, gonads, and placenta
