Tentamen Endocrinologie
,1. Introduction and Recapitulation
1. What are the roles of the endocrine system and the central nervous system?
The endocrine system releases hormones that help control water balance,
metabolism, growth, physical adjustment to the environment, cardiovascular
systems, and reproduction.
The central nervous system also controls the functions of the body and aids in
communication between brain cells, process information, coordinate bodily
functions, metabolism, physical adjustment, and cardiovascular systems. It also
controls and stimulates endocrine systems.
2. Give 2 examples of cooperation between the nervous system and the endocrine
system.
First, the brain relies on hormones produced by the endocrine system to
transmit signals to other tissues regarding metabolism and growth.
Second, the pituitary gland sends messages to the autonomic nervous system,
thereby contributing to the control of blood pressure, heart rate, and breathing.
3. Give some characteristics that the endocrine system and the nervous system have in
common. How do they differ?
Similarities: both systems provide the body with methods to communicate
with internal and external environments in order to coordinate responses.
They both use chemicals to communicate with other cells. They are both
devoted to homeostasis. They are both regulated by negative feedback
mechanisms. There is a very thin line between hormones and
neurotransmitters. Some molecules can function as both (dopamine), and
some cells can secrete both.
Differences: Signal transmission through the nervous system is much faster
than that of the endocrine system.
4. Give an example of how the endocrine system can influence the immune
response.
Estrogen has been shown to regulate immune response by impairing
negative selection of high affinity auto-reactive B cells, modulating B cell
function and leading to Th2 response.
In addition to this, CRH can stimulate cytokine production and
glucocorticoids can block secretion of cytokines.
5. State 4 ways in which cells can communicate with each other. How are these
communication manners named in endocrinology?
- Endocrine function: communication between two cells that are not near each
other; hormone is produced in endocrine cell and is released in the blood; the
hormone leaves the blood to the target and the target cell reacts
, - Autocrine function: cell produces hormone, and that hormone regulates that
cell (the cell itself or similar cells in the same tissues)
- Paracrine function: paracrine cells secrete hormones to other cell types in the
same tissue à helps the cells in a tissue work together
- Neuro-endocrine: nerve cells receive information from other neurons and use
that information to secrete hormones.
- Pheromone function: animals of the same species communicate via scent à
hormones in the air (dogs smell dog pee)
- Allomone function: different species communicate with each other (bees and
flowers)
6. List the hormones secreted by hypothalamic neurons.
• Corticotrophin-releasing hormone (CRH).
• Gonadotrophin-releasing hormone (GnRH).
• Gonadotrophin-inhibiting hormone (GnIH)
• Somatostatin.
• Somatocrinin
• Prolactin-releasing peptide
• Prolactin-inhibiting factor (dopamine)
• Thyrotropin-releasing hormone (TRH).
7. List the hormones secreted by the pituitary gland.
• Adrenocorticotropic hormone (ACTH)
• Follicle-stimulating hormone (FSH)
• Growth hormone (GH)
• Luteinizing hormone (LH)
• Prolactin
• Thyroid-stimulating hormone (TSH)
• Vasopressin
• Oxytocin
8. Based on their molecular structure, 4 types of hormones can be distinguished. Name
these 4 types. Give an example of each type.
- Protein hormones: insulin
- Steroid hormones: cortisol, aldosteron, oestradiol, testosteron
o Derrivatives of cholesterol
- Amine hormones: melatonin, dopamine, adrenaline
- Eicosanoid hormones: prostaglandin, leukotrines, thromboxanes
9. Describe schematically the steps in the synthesis and release of a protein
hormone.
o DNA is transcription of DNA into mRNA
o mRNA is transferred to cytoplasm
o mRNA is translated by ribosomes to a preprohormone
o the preprohormone is moved into the endoplasmic reticulum
o the signal peptide is removed from the preprohormone, so it becomes a
prohormone
, o the prohormone moves to the golgi apparatus where it is packed in
secretory vesicles (granules)
o enzymes in the vesicles cleave peptide sequences from the prohormone so
it becomes the final hormone
§ can also cause glycosylation or phosphorylation
o after a stimulus, the vesicle moves to the edge of the cell and fuses with the
membrane to secrete the hormone (exocytosis)
10. What is the precursor molecule of the catecholamines and what is the precursor
molecule of the sex hormones?
Tyrosine, an amino acid, is the precursor molecule of the catecholamines.
Cholesterol is the precursor for estrogen, testosterone, and progesterone.
Cholesterol à pregnenolone à progesterone à cortisol / aldosterone
/ testosterone
11. What are the three steps involved in a cell's response to a hormonal
stimulus?
The hormone binds to a receptor in or on the cell. Signal transduction
is activated, other molecules are released because of the binding of
the hormone to the receptor. The final messenger can modulate gene
transcription or another process in the cell.
Protein hormones have to bind to a receptor and activate second
messengers. Steroid hormones can diffuse through the lipid bilayer
and act on receptors within the cell à often leads to increased or
decreased transcription.
12. What does the term “half-life” mean? Is the half-life of peptide hormones and
catecholamines a few seconds/minutes or a few hours? Explain.
Half-life means the time it takes for the substance to lose 50% of its activity.
Peptide hormones and catecholamines have a relatively short half-life of a few
seconds to minutes. Since these hormones are not taken up by the targeted
cells, they could keep going around the body and activating cells while this
stimulation is no longer needed. Therefore, they are broken down relatively
quickly, so the response is controlled.
13. What is the relationship between the binding of a hormone to proteins in the plasma
and the half-life of that hormone.
In general, when a hormone is bound to a plasma protein, the half-life is
increased. Binding to a plasma protein protects the hormone from being broken
down by enzymes in the liver.
14. Make a diagram of the three best known transduction pathways:
,a. cAMP formation
Ligand
Adenyl
cyclase
Receptor
ATP cAMP
Inactive Active
PKA PKA
Cellular
Response
b. activation of Phospolipase-C
Ligand
Phospholipase C
DAG
Receptor
PIP2 Protein
kinase C
ER IP3
Calcium
channel Cellular
Response
Ca2+
Ca2+ binding
proteins
c. activation of receptor tyrosine kinases
, Ligand
Tyrosine kinase
domain
Phosphorylated
tyrosine
Receptor
tyrosine kinase
Substrates
15. Name the autocrine/paracrine hormones derived from arachidonic acid. Give some
examples of their biological action.
Prostaglandins, thromboxanes, leukotrienes, and lipoxins. They play a role in
mounting or inhibiting inflammation, allergy, fever. Regulate the abortion of
pregnancy, regulate cell growth, control blood pressure.
16. Which products are produced upon activation of phospholipase D? And upon
activation of phospholipase A2? Why has the pharmaceutical industry such a big
interest in the development of phospolipase A2 antagonists?
The activation of phospholipase D produces soluble choline and phosphatidic
acid. Phospholipase A2 produces lysolecithin and a fatty acid. Both products
serve as precursors for inflammatory mediators. Excessive production of these
mediators is involved in the pathophysiology of numerous diseases including
inflammation, allergy, brain injury, cancer development, and cardiovascular
disorders. Therefore, it might be useful to inhibit phospholipase A2 as a
treatment for these diseases.
17. Name at least 3 factors that determine the outcome of the interaction of a
hormone with its target cell.
The concentration of the hormone, the amount of receptors on the target
cell, and the affinity of the hormone to the receptor, duration of exposure,
and interval between exposure.
,18. What is a transcription factor? How are transcription factors linked to
hormonal actions?
Transcription factors are proteins that are involved in the process of transcribing
DNA into RNA. Steroid hormones can interact with intracellular receptors. These
receptors can then bind to the HREs (hormone responsive elements) in chromatin.
The receptors then interact with other transcription factors. This all leads to
induction or repression of transcription.
19. How does a nuclear receptor function upon stimulation by its hormone ligand?
When nuclear receptors are stimulated by their hormone ligan, most function as a
transcription factor. They have an N terminal transactivation domain, a DNA binding
domain, and a C terminal ligand binding domain. When the ligand binds to the
nuclear receptor, the receptor is directed to the DNA transcription regulation sites.
Then they bind to the DNA and lead to up or down regulation of gene expression.
20. How can hormones be divided into functional groups according to their chemical
structure. How is this classification reflected in their mechanism of action at the
cellular/molecular level?
According to chemical structure, hormones can be divided into three groups: lipid
derived hormones, amino acid derived hormones, and peptide hormones. Steroid
hormones are insoluble in water and are transported by transport proteins in the
blood. They can pass through the phospholipid barrier of the cell and thus bind to a
receptor inside the cell. Amino acid derived hormones are soluble in water and bid
to receptors outside the cell, initiating a signaling cascade within the cell. Peptide
hormones are bigger amino acid hormones but have the same characteristics.
21. How is the structure of the pituitary gland associated with its functions? How is the
pituitary divided into functional terms? Are these division preserved in non-mammal
species? Where is the melanocyte-stimulating hormone produced in adult humans?
In humans, the pituitary gland can be divided into two parts. The anterior lobe
contains cells that secrete various hormones. The secretion of these hormones is
regulated by the hypothalamus, which is closely connected with the lobe through
neurons. The posterior lobe consists of axons from nerve cell bodies in the
hypothalamus. This part secretes and stores two hormones; ADH and ocytocin,
these are produced by the hypothalamus.
All non-human vertebrate species have three lobes of the pituitary. Humans do not
have the intermediate lobe. Instead, MSH is produced in cells dispersed within the
anterior lobe.
22. Name 4 characteristics of the non-classical hormones.
Synthesized at multiple sites
Act locally
Exert opposite activities
Overlapping biological activities
Large repertoire of effects
, 23. Which are the five main groups of hormone receptor proteins?
Nuclear receptors
G-protein coupled receptors
Enzyme linked receptors
Ion channel receptors
Cytokine receptors
24. What does the The Receptor Hypothesis of hormone action state?
Hormone specificity lies in the tissue distribution of the receptor
Introductory concepts
Endocrinology is the study of hormones
Hormones are chemical substances produced by specialized tissues (glands) and secreted
into the blood, where they are carried to a target organ
- However, many substances we call hormones do not fit into this traditional
definition;
o They are involved in other paracrine or autocrine mechanisms that do not
need hormones to be secreted into the blood
o They do not have to be produced by specialized tissues
o They can have more than one target organ
Better definition: A hormone is a chemical, non-nutrient, intercellular messenger that is
effective at micromolar concentrations or less, and carries information between two or
more cells
Major endocrine structures
- Hypothalamus: control of hormone secretions
- Pineal gland: reproductive maturation and body rhythm
- Pituitary gland: induction of hormone secretion; water and salt balance
- Thyroid: growth and development; metabolism
- Adrenal gland: inflammation, salt and carboxylate metabolism, emotional arousal
- Pancreas: sugar metabolism
- Gut: digestion and appetite
- Gonads (testes/ovaries): body development, maintenance of reproductive organs
Types of feedback loops
- Autocrine feedback: the hormone secreted by the endocrine cell leads to negative
feedback to that endocrine cell
- Target cell feedback: the target cell of the hormone produces a molecule that leads
to negative feedback of the endocrine cell
- Brain regulation: the target cell produces a molecule that has an effect on the
hypothalamus which then has an effect on the endocrine cell
,- Brain and pituitary regulation: the hormone secreted by the endocrine cell has an
effect on the hypothalamus and anterior pituitary
, 2. Neuroanatomy of the Hypothalamus and Pituitary Gland
Anatomy of the hypothalamus
Hormoontypen
- Peptiden
o Eiwit structuur
o Grootste en meest diverse groep
o Bind met receptoren op het celmembraan (vaak GPCRs)
o Snelle en tijdelijke respons
- Steroïden
o Derivaten van cholesterol
o Vooral geproduceerd in bijnier en gonaden (geslachtsorgaan)
o Cortisol, aldosteron, testosteron
o Vier ringstructuren
o In vet oplosbaar
o Breed, langzaam, en langdurig bereik
o Gaat naar cytoplasma en bind daar een receptor die vervolgens de nucleus in gaat
- Amines
o Gemodificeerde amino zuren
o Dopamine, catecholamines (noradrenaline & adrenaline)
o Schildklierhormonen (thyroxine, triiodothyronine)
o Bind met receptoren op het celmembraan (vaak GPCRs)
o Snelle en tijdelijke respons
- Eicosanoiden (niet klassieke hormonen)
o Derivaten van vetzuren
o Voornamelijk een lokale functie
o Prostaglandins, leukotrines, thromboxanes
,1. Introduction and Recapitulation
1. What are the roles of the endocrine system and the central nervous system?
The endocrine system releases hormones that help control water balance,
metabolism, growth, physical adjustment to the environment, cardiovascular
systems, and reproduction.
The central nervous system also controls the functions of the body and aids in
communication between brain cells, process information, coordinate bodily
functions, metabolism, physical adjustment, and cardiovascular systems. It also
controls and stimulates endocrine systems.
2. Give 2 examples of cooperation between the nervous system and the endocrine
system.
First, the brain relies on hormones produced by the endocrine system to
transmit signals to other tissues regarding metabolism and growth.
Second, the pituitary gland sends messages to the autonomic nervous system,
thereby contributing to the control of blood pressure, heart rate, and breathing.
3. Give some characteristics that the endocrine system and the nervous system have in
common. How do they differ?
Similarities: both systems provide the body with methods to communicate
with internal and external environments in order to coordinate responses.
They both use chemicals to communicate with other cells. They are both
devoted to homeostasis. They are both regulated by negative feedback
mechanisms. There is a very thin line between hormones and
neurotransmitters. Some molecules can function as both (dopamine), and
some cells can secrete both.
Differences: Signal transmission through the nervous system is much faster
than that of the endocrine system.
4. Give an example of how the endocrine system can influence the immune
response.
Estrogen has been shown to regulate immune response by impairing
negative selection of high affinity auto-reactive B cells, modulating B cell
function and leading to Th2 response.
In addition to this, CRH can stimulate cytokine production and
glucocorticoids can block secretion of cytokines.
5. State 4 ways in which cells can communicate with each other. How are these
communication manners named in endocrinology?
- Endocrine function: communication between two cells that are not near each
other; hormone is produced in endocrine cell and is released in the blood; the
hormone leaves the blood to the target and the target cell reacts
, - Autocrine function: cell produces hormone, and that hormone regulates that
cell (the cell itself or similar cells in the same tissues)
- Paracrine function: paracrine cells secrete hormones to other cell types in the
same tissue à helps the cells in a tissue work together
- Neuro-endocrine: nerve cells receive information from other neurons and use
that information to secrete hormones.
- Pheromone function: animals of the same species communicate via scent à
hormones in the air (dogs smell dog pee)
- Allomone function: different species communicate with each other (bees and
flowers)
6. List the hormones secreted by hypothalamic neurons.
• Corticotrophin-releasing hormone (CRH).
• Gonadotrophin-releasing hormone (GnRH).
• Gonadotrophin-inhibiting hormone (GnIH)
• Somatostatin.
• Somatocrinin
• Prolactin-releasing peptide
• Prolactin-inhibiting factor (dopamine)
• Thyrotropin-releasing hormone (TRH).
7. List the hormones secreted by the pituitary gland.
• Adrenocorticotropic hormone (ACTH)
• Follicle-stimulating hormone (FSH)
• Growth hormone (GH)
• Luteinizing hormone (LH)
• Prolactin
• Thyroid-stimulating hormone (TSH)
• Vasopressin
• Oxytocin
8. Based on their molecular structure, 4 types of hormones can be distinguished. Name
these 4 types. Give an example of each type.
- Protein hormones: insulin
- Steroid hormones: cortisol, aldosteron, oestradiol, testosteron
o Derrivatives of cholesterol
- Amine hormones: melatonin, dopamine, adrenaline
- Eicosanoid hormones: prostaglandin, leukotrines, thromboxanes
9. Describe schematically the steps in the synthesis and release of a protein
hormone.
o DNA is transcription of DNA into mRNA
o mRNA is transferred to cytoplasm
o mRNA is translated by ribosomes to a preprohormone
o the preprohormone is moved into the endoplasmic reticulum
o the signal peptide is removed from the preprohormone, so it becomes a
prohormone
, o the prohormone moves to the golgi apparatus where it is packed in
secretory vesicles (granules)
o enzymes in the vesicles cleave peptide sequences from the prohormone so
it becomes the final hormone
§ can also cause glycosylation or phosphorylation
o after a stimulus, the vesicle moves to the edge of the cell and fuses with the
membrane to secrete the hormone (exocytosis)
10. What is the precursor molecule of the catecholamines and what is the precursor
molecule of the sex hormones?
Tyrosine, an amino acid, is the precursor molecule of the catecholamines.
Cholesterol is the precursor for estrogen, testosterone, and progesterone.
Cholesterol à pregnenolone à progesterone à cortisol / aldosterone
/ testosterone
11. What are the three steps involved in a cell's response to a hormonal
stimulus?
The hormone binds to a receptor in or on the cell. Signal transduction
is activated, other molecules are released because of the binding of
the hormone to the receptor. The final messenger can modulate gene
transcription or another process in the cell.
Protein hormones have to bind to a receptor and activate second
messengers. Steroid hormones can diffuse through the lipid bilayer
and act on receptors within the cell à often leads to increased or
decreased transcription.
12. What does the term “half-life” mean? Is the half-life of peptide hormones and
catecholamines a few seconds/minutes or a few hours? Explain.
Half-life means the time it takes for the substance to lose 50% of its activity.
Peptide hormones and catecholamines have a relatively short half-life of a few
seconds to minutes. Since these hormones are not taken up by the targeted
cells, they could keep going around the body and activating cells while this
stimulation is no longer needed. Therefore, they are broken down relatively
quickly, so the response is controlled.
13. What is the relationship between the binding of a hormone to proteins in the plasma
and the half-life of that hormone.
In general, when a hormone is bound to a plasma protein, the half-life is
increased. Binding to a plasma protein protects the hormone from being broken
down by enzymes in the liver.
14. Make a diagram of the three best known transduction pathways:
,a. cAMP formation
Ligand
Adenyl
cyclase
Receptor
ATP cAMP
Inactive Active
PKA PKA
Cellular
Response
b. activation of Phospolipase-C
Ligand
Phospholipase C
DAG
Receptor
PIP2 Protein
kinase C
ER IP3
Calcium
channel Cellular
Response
Ca2+
Ca2+ binding
proteins
c. activation of receptor tyrosine kinases
, Ligand
Tyrosine kinase
domain
Phosphorylated
tyrosine
Receptor
tyrosine kinase
Substrates
15. Name the autocrine/paracrine hormones derived from arachidonic acid. Give some
examples of their biological action.
Prostaglandins, thromboxanes, leukotrienes, and lipoxins. They play a role in
mounting or inhibiting inflammation, allergy, fever. Regulate the abortion of
pregnancy, regulate cell growth, control blood pressure.
16. Which products are produced upon activation of phospholipase D? And upon
activation of phospholipase A2? Why has the pharmaceutical industry such a big
interest in the development of phospolipase A2 antagonists?
The activation of phospholipase D produces soluble choline and phosphatidic
acid. Phospholipase A2 produces lysolecithin and a fatty acid. Both products
serve as precursors for inflammatory mediators. Excessive production of these
mediators is involved in the pathophysiology of numerous diseases including
inflammation, allergy, brain injury, cancer development, and cardiovascular
disorders. Therefore, it might be useful to inhibit phospholipase A2 as a
treatment for these diseases.
17. Name at least 3 factors that determine the outcome of the interaction of a
hormone with its target cell.
The concentration of the hormone, the amount of receptors on the target
cell, and the affinity of the hormone to the receptor, duration of exposure,
and interval between exposure.
,18. What is a transcription factor? How are transcription factors linked to
hormonal actions?
Transcription factors are proteins that are involved in the process of transcribing
DNA into RNA. Steroid hormones can interact with intracellular receptors. These
receptors can then bind to the HREs (hormone responsive elements) in chromatin.
The receptors then interact with other transcription factors. This all leads to
induction or repression of transcription.
19. How does a nuclear receptor function upon stimulation by its hormone ligand?
When nuclear receptors are stimulated by their hormone ligan, most function as a
transcription factor. They have an N terminal transactivation domain, a DNA binding
domain, and a C terminal ligand binding domain. When the ligand binds to the
nuclear receptor, the receptor is directed to the DNA transcription regulation sites.
Then they bind to the DNA and lead to up or down regulation of gene expression.
20. How can hormones be divided into functional groups according to their chemical
structure. How is this classification reflected in their mechanism of action at the
cellular/molecular level?
According to chemical structure, hormones can be divided into three groups: lipid
derived hormones, amino acid derived hormones, and peptide hormones. Steroid
hormones are insoluble in water and are transported by transport proteins in the
blood. They can pass through the phospholipid barrier of the cell and thus bind to a
receptor inside the cell. Amino acid derived hormones are soluble in water and bid
to receptors outside the cell, initiating a signaling cascade within the cell. Peptide
hormones are bigger amino acid hormones but have the same characteristics.
21. How is the structure of the pituitary gland associated with its functions? How is the
pituitary divided into functional terms? Are these division preserved in non-mammal
species? Where is the melanocyte-stimulating hormone produced in adult humans?
In humans, the pituitary gland can be divided into two parts. The anterior lobe
contains cells that secrete various hormones. The secretion of these hormones is
regulated by the hypothalamus, which is closely connected with the lobe through
neurons. The posterior lobe consists of axons from nerve cell bodies in the
hypothalamus. This part secretes and stores two hormones; ADH and ocytocin,
these are produced by the hypothalamus.
All non-human vertebrate species have three lobes of the pituitary. Humans do not
have the intermediate lobe. Instead, MSH is produced in cells dispersed within the
anterior lobe.
22. Name 4 characteristics of the non-classical hormones.
Synthesized at multiple sites
Act locally
Exert opposite activities
Overlapping biological activities
Large repertoire of effects
, 23. Which are the five main groups of hormone receptor proteins?
Nuclear receptors
G-protein coupled receptors
Enzyme linked receptors
Ion channel receptors
Cytokine receptors
24. What does the The Receptor Hypothesis of hormone action state?
Hormone specificity lies in the tissue distribution of the receptor
Introductory concepts
Endocrinology is the study of hormones
Hormones are chemical substances produced by specialized tissues (glands) and secreted
into the blood, where they are carried to a target organ
- However, many substances we call hormones do not fit into this traditional
definition;
o They are involved in other paracrine or autocrine mechanisms that do not
need hormones to be secreted into the blood
o They do not have to be produced by specialized tissues
o They can have more than one target organ
Better definition: A hormone is a chemical, non-nutrient, intercellular messenger that is
effective at micromolar concentrations or less, and carries information between two or
more cells
Major endocrine structures
- Hypothalamus: control of hormone secretions
- Pineal gland: reproductive maturation and body rhythm
- Pituitary gland: induction of hormone secretion; water and salt balance
- Thyroid: growth and development; metabolism
- Adrenal gland: inflammation, salt and carboxylate metabolism, emotional arousal
- Pancreas: sugar metabolism
- Gut: digestion and appetite
- Gonads (testes/ovaries): body development, maintenance of reproductive organs
Types of feedback loops
- Autocrine feedback: the hormone secreted by the endocrine cell leads to negative
feedback to that endocrine cell
- Target cell feedback: the target cell of the hormone produces a molecule that leads
to negative feedback of the endocrine cell
- Brain regulation: the target cell produces a molecule that has an effect on the
hypothalamus which then has an effect on the endocrine cell
,- Brain and pituitary regulation: the hormone secreted by the endocrine cell has an
effect on the hypothalamus and anterior pituitary
, 2. Neuroanatomy of the Hypothalamus and Pituitary Gland
Anatomy of the hypothalamus
Hormoontypen
- Peptiden
o Eiwit structuur
o Grootste en meest diverse groep
o Bind met receptoren op het celmembraan (vaak GPCRs)
o Snelle en tijdelijke respons
- Steroïden
o Derivaten van cholesterol
o Vooral geproduceerd in bijnier en gonaden (geslachtsorgaan)
o Cortisol, aldosteron, testosteron
o Vier ringstructuren
o In vet oplosbaar
o Breed, langzaam, en langdurig bereik
o Gaat naar cytoplasma en bind daar een receptor die vervolgens de nucleus in gaat
- Amines
o Gemodificeerde amino zuren
o Dopamine, catecholamines (noradrenaline & adrenaline)
o Schildklierhormonen (thyroxine, triiodothyronine)
o Bind met receptoren op het celmembraan (vaak GPCRs)
o Snelle en tijdelijke respons
- Eicosanoiden (niet klassieke hormonen)
o Derivaten van vetzuren
o Voornamelijk een lokale functie
o Prostaglandins, leukotrines, thromboxanes
