ENDOCRINOLOGY // LECTURE 1 // PART 1 //
INTRODUCTION TO ENDOCRINOLOGY // 16-3-2021
➢ History of endocrinology
- In the 19th century, most organs were described in detail
- Function of glands were unknown
- Berthold’s’ experiment: presence of hormones
➢ First endocrine experiment (1849)
→ He used 4 groups of roosters → The first group were roosters that didn’t get any
treatment the second group were roosters from which both of the testis were removed and
in the third group he removed one of the testis and the other one was placed in the
abdominal cavity and in the fourth group he removed one of the testis and the other one
was placed in the abdominal cavity of another rooster
→ The outcome of this experiment → See the results section of the picture
→ Conclusion: Testis produces something that conditions the blood
→ This conditioned blood caused the changes in the male
→ Years later: Hormone of the testis: Testosterone (1935)
➢ Some important endocrinological break throughs
• Discovery of secretin (1902) by Bayliss and Starling
→ Secretin was produced by the small intestines and induces the production of
endocrine juices in the pancreas which then help with digesting food in the intestines
• Discovery of insulin
- Removal of pancreas in dogs: Diabetes like symptoms in these dogs (Von Mering and
Minkowsky, 1889)
- Role of islets of Langerhans and isolation of insulin (Banting and Best, 1922)
• Discovery of neurotransmitters (Otto Loewi, 1921)
➢ Discovery of the role of the hypothalamus and pituitary gland
• Regulation of the pituitary gland by the hypothalamus
• TRH (Thyroid Releasing Hormone) → First discovered releasing hormone
- Sheep (Guillemin)
- Pig (Schally)
• Inhibition/releasing hormones → Have been discovered later on
➢ Development new techniques
• RIA (radioimmunoassay) by Rosalyn Yalow (Noble prize 1977)
- Measuring hormone concentration in the plasma without the need of expensive time
consuming and unfriendly bio essays
, • Molecular biology
- Genes hormones
- Genes receptors
- Overexpression and knock-out hormones/receptors
➢ Endocrine system
→ It’s a simple system, but there are some mechanisms that can induce complexity to the
system
→ We have an endocrine cell, for example the pituitary gland, which produces a hormone in
the bloodstream → This hormone travels to tissues at a distance where it can bind to its
receptors in various organs → For example the testis or the ovary → Then it sets on motions
in response of the testis or the ovary
→ The endocrine system is not the same as the exocrine system → The exocrine gland
delivers products to a duct that leads to the lumen of another organ, e.g. intestines
→ Products of the exocrine system don’t enter the bloodstream
➢ Hormone release
→ Endocrine means that the cell produces a hormone which is released in to the blood
stream and has an effect on distant cells or organs
→ Neuroendocrine means that the neuron produces a hormone which is released in to the
blood stream and has also an effect on distant cells or organs
→ Paracrine means that the cell produces a factor which affects the neighboring cells
→ Autocrine means that the cell produces a factor which affects itself
→ Neurocrine means that the neuron produces a factor which affects other neurons
➢ Introduction in endocrinology
→ Two intercellular communication systems that control physiology
→ Endocrinology is an important communication system of the body, but it’s not the only
system → The nervous system is also very important communication system of the body
which affects various organs just like the endocrine system
→ Many organs are therefore affected by both systems and these systems are therefore
tightly interconnected
, ➢ Homeostasis
• Homeostasis = The regulation and maintenance of a balance, so that the state of
the internal environment in the body (blood and tissue fluids) remains stable
• As soon as a certain value (e.g. blood glucose level or body temperature) deviates
from the norm, the body takes action
→ Almost all endocrine systems work through this negative feedback
→ Homeostasis and endocrinology is mainly regulated by negative feedback systems → This
means that a hormone or metabolite which is increased in the circulation is sensed by the
endocrine tissue which then produces a hormone which affects the target tissue so that it
produces less metabolites or hormones and so that hormone concentrations or metabolites
concentration decrease
➢ Homeostasis, negative feedback
→ Due to food intake blood glucose levels are increased and is sensed by pancreatic beta
cells which starts producing insulin which make a decrease in blood glucose because blood
glucose is taken up by the liver
➢ Homeostasis, negative feedback // 2 hormone systems
→ This is an example of how negative feedback can be regulated by 2 hormone systems
→ If we have a decreased metabolite which is sensed by endocrine tissue A → This tissue A
then starts to producing hormone A and affects the target tissue so that there’s an increased
production of the metabolites → The increased production is then sensed in endocrine
tissue B which then starts producing hormone B which then decreases the production of the
metabolite by the target tissue
→ This example deals with blood calcium levels → If blood calcium levels are increased due
to dietary intake this is sensed in the parafollicular cells in the thyroid gland → These cells
starts to produce calcitonin which makes sure that calcium is taken up by the bone tissue
→ If we have decreased levels of blood calcium, for example due to loss of calcium via the
intestines of the kidney this is sensed in the parthood glands which produces the
parathormone which makes sure that the bone release calcium in the blood stream so that
the blood calcium is increased
, ➢ Homeostasis
→ Although homeostasis is mainly regulated by negative feedback systems, there are also
positive hormone feedback systems which results in a metabolite / hormone which is
increased which is sensed by the endocrine system which produces a hormone which has
further increase in the hormone metabolite
→ So there’s positive feedback systems in which a metabolite is increased which increases
the hormone which in turn increases the metabolite
→ These positive feedback systems can only take place if there’s a certain event which stops
the circle
→ One of the systems in which positive feedback takes place is during ovulation → During
ovulation is an increase in the production of estrogens which then increases the production
of FSH / LH which then increases the production of estrogen → This circle is ongoing until
certain levels of estrogens after which ovulation is induced and the positive feedback cycle is
stopped
➢ Hormone categories
• Protein hormones
• Steroid hormones
➢ Protein hormones
• Protein hormones: amino acids
- 3- > 180 aa
- Linear / ring structure
- Linear: double/single chain
- Monomer / dimer
- Special adaptations
o Sulphation of tyrosine
o Glutamate pyrrole structure
o Carbohydrates (glycoproteins)
- Isoforms (gene level / post transcription level)
- Hydrophile: can’t diffuse in to the cell: Extracellular receptor
➢ Synthesis of protein hormones
→ DNA-transcription / mRNA translation and formation of hormone
→ Preprohormone → Prohormone → Hormone
→ This picture shows the preprohormone biosynthesis → At the end the hormone is
secreted in to secretory granules
, ➢ Hormone secretion: protein hormones
→ Hormones are produced in the ER and in the Golgi apparatus → Finally the final hormone
is released in to secretory granules and can be stored inside the cell for a longer period of
time → This means that there’s a pool of hormones present in the cells → After fusion of the
granules with the cell membrane hormones can be released in to the circulation
→ So when there’s stimulus that induces hormone production the intracellular Ca2+ will
increase which results in fusion of the secretory granules with the cell membrane and in
exocytosis → That means that the pool of hormones which were present in the secretory
granules are now released in to the circulation
➢ Hormone circulation and metabolism
→ Protein hormones: Broken down in to inactive metabolites → Usually short half-life
→ There are a lot of proteinases in the plasma which are enzymes that break down proteins
→ These enzymes can cut proteins in to inactive substances
→ In this picture you see some of these proteinases
➢ Mechanisms of hormone effects
→ A receptor only binds 1 specific hormone → Ligand binding specificity
→ There are receptor isoforms → Induce different cell responses
→ Receptor agonist binds to receptor and mimics a hormone
→ Receptor antagonist occupies a receptor and prevents activation of the receptor by the
hormone
→ Binding of a hormone to a receptor results in intracellular signaling and that results in the
response of the cell
➢ Plasma membrane receptors / extracellular receptors
→ All protein hormones have extracellular receptors and these are mainly the G-protein
coupled receptors
→ Extracellular receptors:
- Channel bound receptors
- G-protein coupled receptors
- Enzyme-linked receptors / enzyme receptors
, ➢ G-protein coupled receptor
→ G-protein coupled receptors have a transmembrane part → They have an extracellular
part to which the hormone can bind and an intracellular part to which the G-protein can be
coupled
→ When a protein hormone binds to its receptor GDP (G-protein) is phosphorylated in to
GTP which then leaves the receptor and binds to an effector enzyme which in this case is
adenylic cyclase → The effector enzyme is then activated so that cAMP is formed from ATP
→ cAMP is a second messenger which has an effect on cellular function
→ There are different G-proteins
→ Classification G-proteins:
- G-protein that activates effector enzyme (Gs)
- G-protein that inhibits effector enzyme (Gi)
- Various G-proteins are known
→ There are also different effector enzymes:
- Adenylyl cyclase
- Guanylyl cyclase
→ They form the second messenger cAMP or cGMP
➢ Different protein hormones
• Neurotransmitters: Synthesized by neurons, released and influences directly
neighboring cells (nerve cells, muscle, secretory cell)
- Neurotransmitters as hormone: dopamine
• Neuropeptides: Peptide hormone produced by nerve cell (oxytocin, CRH, GnRH)
• Growth factors: Peptide hormones that regulate growth activity (NGF, TGF-beta,
EGF)
➢ Steroid hormones
→ Steroid hormones are derived from steroids which are lipids with 4 characteristic
carbon ring structures
→ Sex hormones
→ Hormones of the adrenal cortex
→ All steroid hormones are derived from cholesterol and can diffuse in to a cell and all
have an intracellular receptor
➢ Hormone secretion
→ The hormone secretion of steroid hormones is different than that of protein hormones
INTRODUCTION TO ENDOCRINOLOGY // 16-3-2021
➢ History of endocrinology
- In the 19th century, most organs were described in detail
- Function of glands were unknown
- Berthold’s’ experiment: presence of hormones
➢ First endocrine experiment (1849)
→ He used 4 groups of roosters → The first group were roosters that didn’t get any
treatment the second group were roosters from which both of the testis were removed and
in the third group he removed one of the testis and the other one was placed in the
abdominal cavity and in the fourth group he removed one of the testis and the other one
was placed in the abdominal cavity of another rooster
→ The outcome of this experiment → See the results section of the picture
→ Conclusion: Testis produces something that conditions the blood
→ This conditioned blood caused the changes in the male
→ Years later: Hormone of the testis: Testosterone (1935)
➢ Some important endocrinological break throughs
• Discovery of secretin (1902) by Bayliss and Starling
→ Secretin was produced by the small intestines and induces the production of
endocrine juices in the pancreas which then help with digesting food in the intestines
• Discovery of insulin
- Removal of pancreas in dogs: Diabetes like symptoms in these dogs (Von Mering and
Minkowsky, 1889)
- Role of islets of Langerhans and isolation of insulin (Banting and Best, 1922)
• Discovery of neurotransmitters (Otto Loewi, 1921)
➢ Discovery of the role of the hypothalamus and pituitary gland
• Regulation of the pituitary gland by the hypothalamus
• TRH (Thyroid Releasing Hormone) → First discovered releasing hormone
- Sheep (Guillemin)
- Pig (Schally)
• Inhibition/releasing hormones → Have been discovered later on
➢ Development new techniques
• RIA (radioimmunoassay) by Rosalyn Yalow (Noble prize 1977)
- Measuring hormone concentration in the plasma without the need of expensive time
consuming and unfriendly bio essays
, • Molecular biology
- Genes hormones
- Genes receptors
- Overexpression and knock-out hormones/receptors
➢ Endocrine system
→ It’s a simple system, but there are some mechanisms that can induce complexity to the
system
→ We have an endocrine cell, for example the pituitary gland, which produces a hormone in
the bloodstream → This hormone travels to tissues at a distance where it can bind to its
receptors in various organs → For example the testis or the ovary → Then it sets on motions
in response of the testis or the ovary
→ The endocrine system is not the same as the exocrine system → The exocrine gland
delivers products to a duct that leads to the lumen of another organ, e.g. intestines
→ Products of the exocrine system don’t enter the bloodstream
➢ Hormone release
→ Endocrine means that the cell produces a hormone which is released in to the blood
stream and has an effect on distant cells or organs
→ Neuroendocrine means that the neuron produces a hormone which is released in to the
blood stream and has also an effect on distant cells or organs
→ Paracrine means that the cell produces a factor which affects the neighboring cells
→ Autocrine means that the cell produces a factor which affects itself
→ Neurocrine means that the neuron produces a factor which affects other neurons
➢ Introduction in endocrinology
→ Two intercellular communication systems that control physiology
→ Endocrinology is an important communication system of the body, but it’s not the only
system → The nervous system is also very important communication system of the body
which affects various organs just like the endocrine system
→ Many organs are therefore affected by both systems and these systems are therefore
tightly interconnected
, ➢ Homeostasis
• Homeostasis = The regulation and maintenance of a balance, so that the state of
the internal environment in the body (blood and tissue fluids) remains stable
• As soon as a certain value (e.g. blood glucose level or body temperature) deviates
from the norm, the body takes action
→ Almost all endocrine systems work through this negative feedback
→ Homeostasis and endocrinology is mainly regulated by negative feedback systems → This
means that a hormone or metabolite which is increased in the circulation is sensed by the
endocrine tissue which then produces a hormone which affects the target tissue so that it
produces less metabolites or hormones and so that hormone concentrations or metabolites
concentration decrease
➢ Homeostasis, negative feedback
→ Due to food intake blood glucose levels are increased and is sensed by pancreatic beta
cells which starts producing insulin which make a decrease in blood glucose because blood
glucose is taken up by the liver
➢ Homeostasis, negative feedback // 2 hormone systems
→ This is an example of how negative feedback can be regulated by 2 hormone systems
→ If we have a decreased metabolite which is sensed by endocrine tissue A → This tissue A
then starts to producing hormone A and affects the target tissue so that there’s an increased
production of the metabolites → The increased production is then sensed in endocrine
tissue B which then starts producing hormone B which then decreases the production of the
metabolite by the target tissue
→ This example deals with blood calcium levels → If blood calcium levels are increased due
to dietary intake this is sensed in the parafollicular cells in the thyroid gland → These cells
starts to produce calcitonin which makes sure that calcium is taken up by the bone tissue
→ If we have decreased levels of blood calcium, for example due to loss of calcium via the
intestines of the kidney this is sensed in the parthood glands which produces the
parathormone which makes sure that the bone release calcium in the blood stream so that
the blood calcium is increased
, ➢ Homeostasis
→ Although homeostasis is mainly regulated by negative feedback systems, there are also
positive hormone feedback systems which results in a metabolite / hormone which is
increased which is sensed by the endocrine system which produces a hormone which has
further increase in the hormone metabolite
→ So there’s positive feedback systems in which a metabolite is increased which increases
the hormone which in turn increases the metabolite
→ These positive feedback systems can only take place if there’s a certain event which stops
the circle
→ One of the systems in which positive feedback takes place is during ovulation → During
ovulation is an increase in the production of estrogens which then increases the production
of FSH / LH which then increases the production of estrogen → This circle is ongoing until
certain levels of estrogens after which ovulation is induced and the positive feedback cycle is
stopped
➢ Hormone categories
• Protein hormones
• Steroid hormones
➢ Protein hormones
• Protein hormones: amino acids
- 3- > 180 aa
- Linear / ring structure
- Linear: double/single chain
- Monomer / dimer
- Special adaptations
o Sulphation of tyrosine
o Glutamate pyrrole structure
o Carbohydrates (glycoproteins)
- Isoforms (gene level / post transcription level)
- Hydrophile: can’t diffuse in to the cell: Extracellular receptor
➢ Synthesis of protein hormones
→ DNA-transcription / mRNA translation and formation of hormone
→ Preprohormone → Prohormone → Hormone
→ This picture shows the preprohormone biosynthesis → At the end the hormone is
secreted in to secretory granules
, ➢ Hormone secretion: protein hormones
→ Hormones are produced in the ER and in the Golgi apparatus → Finally the final hormone
is released in to secretory granules and can be stored inside the cell for a longer period of
time → This means that there’s a pool of hormones present in the cells → After fusion of the
granules with the cell membrane hormones can be released in to the circulation
→ So when there’s stimulus that induces hormone production the intracellular Ca2+ will
increase which results in fusion of the secretory granules with the cell membrane and in
exocytosis → That means that the pool of hormones which were present in the secretory
granules are now released in to the circulation
➢ Hormone circulation and metabolism
→ Protein hormones: Broken down in to inactive metabolites → Usually short half-life
→ There are a lot of proteinases in the plasma which are enzymes that break down proteins
→ These enzymes can cut proteins in to inactive substances
→ In this picture you see some of these proteinases
➢ Mechanisms of hormone effects
→ A receptor only binds 1 specific hormone → Ligand binding specificity
→ There are receptor isoforms → Induce different cell responses
→ Receptor agonist binds to receptor and mimics a hormone
→ Receptor antagonist occupies a receptor and prevents activation of the receptor by the
hormone
→ Binding of a hormone to a receptor results in intracellular signaling and that results in the
response of the cell
➢ Plasma membrane receptors / extracellular receptors
→ All protein hormones have extracellular receptors and these are mainly the G-protein
coupled receptors
→ Extracellular receptors:
- Channel bound receptors
- G-protein coupled receptors
- Enzyme-linked receptors / enzyme receptors
, ➢ G-protein coupled receptor
→ G-protein coupled receptors have a transmembrane part → They have an extracellular
part to which the hormone can bind and an intracellular part to which the G-protein can be
coupled
→ When a protein hormone binds to its receptor GDP (G-protein) is phosphorylated in to
GTP which then leaves the receptor and binds to an effector enzyme which in this case is
adenylic cyclase → The effector enzyme is then activated so that cAMP is formed from ATP
→ cAMP is a second messenger which has an effect on cellular function
→ There are different G-proteins
→ Classification G-proteins:
- G-protein that activates effector enzyme (Gs)
- G-protein that inhibits effector enzyme (Gi)
- Various G-proteins are known
→ There are also different effector enzymes:
- Adenylyl cyclase
- Guanylyl cyclase
→ They form the second messenger cAMP or cGMP
➢ Different protein hormones
• Neurotransmitters: Synthesized by neurons, released and influences directly
neighboring cells (nerve cells, muscle, secretory cell)
- Neurotransmitters as hormone: dopamine
• Neuropeptides: Peptide hormone produced by nerve cell (oxytocin, CRH, GnRH)
• Growth factors: Peptide hormones that regulate growth activity (NGF, TGF-beta,
EGF)
➢ Steroid hormones
→ Steroid hormones are derived from steroids which are lipids with 4 characteristic
carbon ring structures
→ Sex hormones
→ Hormones of the adrenal cortex
→ All steroid hormones are derived from cholesterol and can diffuse in to a cell and all
have an intracellular receptor
➢ Hormone secretion
→ The hormone secretion of steroid hormones is different than that of protein hormones
