Endocrinology
Introduction endocrinology - Haas
In the 19th century, most organs were described in detail.
Function of glands was unknown.
Berthold was the first to perform an endocrinology experiment → showed the presence of
hormones.
Berthold used 4 groups of roosters:
• Roosters without treatment → grew up as normal roosters: normal comb and wattles,
interest in hens, normal crow and aggressive fight behaviour
• Roosters with both testis removed → grew up as small roosters: small combs and wattles, no
interest in hens, weak crow and little fight behaviour
• Roosters with one testis removed, the other one was placed in the abdominal cavity →
normal rooster
• Roosters with one testis removed, the other testis was placed in the abdominal cavity of
another rooster → normal rooster
Conclusion: the testis produces something that conditions the blood. This conditioned blood caused
the changes in the male.
Years later (1935) the hormone of the testis was discovered → testosterone
Discovery of secretin in 1902 by Bayliss and Starling.
Secretin produced by the small intestine and induces the production of endocrine juices in the
pancreas which help by digesting food in the intestines.
Discovery of insulin:
Removal of pancreas in dogs: diabetes like symptoms (Von Mering and Minkowsky, 1889)
Role of islets of Langerhans and isolation of insulin (Banting and Best, 1922). Islets of Langerhans
protect these dogs from diabetes and insulin lowers glucose levels of blood.
Discovery of neurotransmitters (Otto Loewi,1921).
Regulation of the pituitary gland discovered. First discovered releasing hormone: TRH. Discovered in
sheep (Guillemin) and pig (Schally).
RIA = radioimmunoassay discovered by Rosalyn Yalow. Can measure hormone concentration in the
plasma without the need of time consuming and animal unfriendly bioassays.
Molecular biology
• Genes hormones
• Genes receptors
• Overexpression and knock-out hormones/receptors
Simple endocrine system:
Endocrine cell produces a hormone into the bloodstream. This hormone travels to tissue at a
distance where it can bind to its receptor in various organs (e.g. testis/overy).
Exocrine gland: deliver products to a duct that leads to the lumen of another organ, e.g. intestines.
Products do not enter the bloodstream.
Endocrine = cell produces hormone which is releases in the blood stream and has effect on distant
cells or organs.
Neuroendocrine = neuron produces hormone which is released in blood stream and also has effect
on distant cells or organs.
Paracrine = cell produces a factor which affects the neighbouring cells.
1
,Autocrine = cell produces a factor which affects itself.chi
Neurocrine = neuron produces a factor which affects other neurons.
Nervous system is also a very important communication system in the body → affects various
organs.
Most organs are affected by both the nervous system and the endocrine system – systems are tightly
interconnected.
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.
Homeostasis and endocrine systems are mainly regulated by negative feedback systems. A hormone
or metabolite which is increased in circulation is sensed by endocrine tissue which now produces a
hormone which affects the targets tissue so this starts producing less metabolites and hormones –
concentration of hormones/metabolites decreased.
Blood glucose levels are increased after food intake → sensed pancreatic β cells which start
producing insulin → decreasing blood glucose since glucose is taken up by liver.
Negative feedback by 2 hormone systems
Decreased metabolite sensed by endocrine tissue A → starts producing hormone A and affects the
target tissue → increased production of metabolite → sensed by endocrine tissue B starts producing
hormone A→ decreases production of metabolite.
Example:
Blood calcium levels increase due to dietary intake, sensed in parafollicular cells → starts producing
calcitonin: makes sure that calcium is taken up by the bone tissue.
Decreased level of blood calcium, sensed by parathyroid glands → starts producing parathormone:
makes sure that the bone releases calcium into the blood stream → blood calcium increased.
There are also positive hormone feedback system: metabolite increased, sensed by endocrine tissue
→ produces hormone which increases metabolite.
2
,Can only take place if there is a certain event which stops the viscous circle.
During ovulation: increased production of estrogens → increased production of FSH/LH which in turn
increase the estrogens. This process is ungoing until certain levels of estrogens are reached after
which ovulation is induced.
Hormone categories
• Protein hormones
• Steroid 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)
• Hydrophyl: Cannot diffuse into the cell: Extracellular receptor
Synthesis of protein hormones
DNA-transcription/mRNA translation and
formation of hormone.
Preprohormone → prohormone → hormone
Preprohormone and prohormone made in ER and
golgi.
The hormone is secreted into secretory granules
and can be stored inside the cell → pool of
hormones.
Stimulus induces hormone production →
intracellular calcium levels increases → fusion of
secretory granules with cell membrane →
exocytosis. Pool of hormones are released into the circulation.
The half life of these protein hormones is very short due to the high amount of proteinases in the
plasma – enzymes that breakdown proteins into inactive substances.
Protein hormones bind to extracellular receptors and these receptors are present in the cell
membrane.
3
, Binding of a hormone to a receptor → intracellular signalling → response of the cell.
A receptor only binds 1 specific hormone (ligand binding specificity).
A receptor can have different isoforms (e.g. estrogen receptor).
Receptor agonist: factor that binds to the receptor and mimics a hormone.
Receptor antagonist: factors that occupies a receptor and prevents binding of the hormone to the
receptor → prevents activation of the receptor by the hormone.
All protein hormones have extracellular receptors.
Mainly are G protein-coupled receptors, but can also be channel bound receptors
or enzyme-linked receptors.
G protein-coupled receptors have a transmembrane part, extracellular part to
which the hormone can bind and an intracellular part to which the G protein can
be coupled.
G-protein interaction with Carboxy terminus 3rd intracellular loop.
When a protein hormone binds to its receptor, GDP is phosphorylated
to GTP. GTP leaves the receptor and binds to an effector enzyme
(adenylyl cyclase). Effector enzyme activated: second messenger cAMP
formed from ATP.
Another effector enzyme can be guanylyl cyclase which forms cGMP.
Different G-proteins:
• G-protein that activates effector enzyme (Gs)
• G-protein that inhibits effector enzyme (Gi)
Protein hormones
• Neurotransmitters: synthesized by neurons, released and
influences directly neighboring cells (nerve cell, muscle,
secretory cell)
o 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
Derived by steroids: lipids with 4 characteristic carbon ring structures.
Sex hormones and hormones of the adrenal cortex.
All steroid hormones are derived from cholesterol → can diffuse into the cell and all have an
intracellular receptor.
Mechanism of hormone secretion for steroid hormones is different from that of protein hormones.
Steroid hormones are lipid hormones and can exit cell by passive diffusion. Almost no storage of
hormones in the cell, some storage by fat droplets.
Speed of production is speed of delivery → Speed of production is controlled
Steroid hormones bind to intracellular receptor after diffusion into cell. This hormone-receptor
complex travels to nucleus where it is able to bind to binding domain in the promotor → results in
gene expression.
Steroid hormones are not able to dissolve in the watery plasma, but are coupled to transport
proteins to be able to circulate in the plasma. They are not cut into bioactive substances into the
plasma, but transported to the liver where they are sulphated or converted into glucuronic acid to
become bio inactive.
4
Introduction endocrinology - Haas
In the 19th century, most organs were described in detail.
Function of glands was unknown.
Berthold was the first to perform an endocrinology experiment → showed the presence of
hormones.
Berthold used 4 groups of roosters:
• Roosters without treatment → grew up as normal roosters: normal comb and wattles,
interest in hens, normal crow and aggressive fight behaviour
• Roosters with both testis removed → grew up as small roosters: small combs and wattles, no
interest in hens, weak crow and little fight behaviour
• Roosters with one testis removed, the other one was placed in the abdominal cavity →
normal rooster
• Roosters with one testis removed, the other testis was placed in the abdominal cavity of
another rooster → normal rooster
Conclusion: the testis produces something that conditions the blood. This conditioned blood caused
the changes in the male.
Years later (1935) the hormone of the testis was discovered → testosterone
Discovery of secretin in 1902 by Bayliss and Starling.
Secretin produced by the small intestine and induces the production of endocrine juices in the
pancreas which help by digesting food in the intestines.
Discovery of insulin:
Removal of pancreas in dogs: diabetes like symptoms (Von Mering and Minkowsky, 1889)
Role of islets of Langerhans and isolation of insulin (Banting and Best, 1922). Islets of Langerhans
protect these dogs from diabetes and insulin lowers glucose levels of blood.
Discovery of neurotransmitters (Otto Loewi,1921).
Regulation of the pituitary gland discovered. First discovered releasing hormone: TRH. Discovered in
sheep (Guillemin) and pig (Schally).
RIA = radioimmunoassay discovered by Rosalyn Yalow. Can measure hormone concentration in the
plasma without the need of time consuming and animal unfriendly bioassays.
Molecular biology
• Genes hormones
• Genes receptors
• Overexpression and knock-out hormones/receptors
Simple endocrine system:
Endocrine cell produces a hormone into the bloodstream. This hormone travels to tissue at a
distance where it can bind to its receptor in various organs (e.g. testis/overy).
Exocrine gland: deliver products to a duct that leads to the lumen of another organ, e.g. intestines.
Products do not enter the bloodstream.
Endocrine = cell produces hormone which is releases in the blood stream and has effect on distant
cells or organs.
Neuroendocrine = neuron produces hormone which is released in blood stream and also has effect
on distant cells or organs.
Paracrine = cell produces a factor which affects the neighbouring cells.
1
,Autocrine = cell produces a factor which affects itself.chi
Neurocrine = neuron produces a factor which affects other neurons.
Nervous system is also a very important communication system in the body → affects various
organs.
Most organs are affected by both the nervous system and the endocrine system – systems are tightly
interconnected.
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.
Homeostasis and endocrine systems are mainly regulated by negative feedback systems. A hormone
or metabolite which is increased in circulation is sensed by endocrine tissue which now produces a
hormone which affects the targets tissue so this starts producing less metabolites and hormones –
concentration of hormones/metabolites decreased.
Blood glucose levels are increased after food intake → sensed pancreatic β cells which start
producing insulin → decreasing blood glucose since glucose is taken up by liver.
Negative feedback by 2 hormone systems
Decreased metabolite sensed by endocrine tissue A → starts producing hormone A and affects the
target tissue → increased production of metabolite → sensed by endocrine tissue B starts producing
hormone A→ decreases production of metabolite.
Example:
Blood calcium levels increase due to dietary intake, sensed in parafollicular cells → starts producing
calcitonin: makes sure that calcium is taken up by the bone tissue.
Decreased level of blood calcium, sensed by parathyroid glands → starts producing parathormone:
makes sure that the bone releases calcium into the blood stream → blood calcium increased.
There are also positive hormone feedback system: metabolite increased, sensed by endocrine tissue
→ produces hormone which increases metabolite.
2
,Can only take place if there is a certain event which stops the viscous circle.
During ovulation: increased production of estrogens → increased production of FSH/LH which in turn
increase the estrogens. This process is ungoing until certain levels of estrogens are reached after
which ovulation is induced.
Hormone categories
• Protein hormones
• Steroid 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)
• Hydrophyl: Cannot diffuse into the cell: Extracellular receptor
Synthesis of protein hormones
DNA-transcription/mRNA translation and
formation of hormone.
Preprohormone → prohormone → hormone
Preprohormone and prohormone made in ER and
golgi.
The hormone is secreted into secretory granules
and can be stored inside the cell → pool of
hormones.
Stimulus induces hormone production →
intracellular calcium levels increases → fusion of
secretory granules with cell membrane →
exocytosis. Pool of hormones are released into the circulation.
The half life of these protein hormones is very short due to the high amount of proteinases in the
plasma – enzymes that breakdown proteins into inactive substances.
Protein hormones bind to extracellular receptors and these receptors are present in the cell
membrane.
3
, Binding of a hormone to a receptor → intracellular signalling → response of the cell.
A receptor only binds 1 specific hormone (ligand binding specificity).
A receptor can have different isoforms (e.g. estrogen receptor).
Receptor agonist: factor that binds to the receptor and mimics a hormone.
Receptor antagonist: factors that occupies a receptor and prevents binding of the hormone to the
receptor → prevents activation of the receptor by the hormone.
All protein hormones have extracellular receptors.
Mainly are G protein-coupled receptors, but can also be channel bound receptors
or enzyme-linked receptors.
G protein-coupled receptors have a transmembrane part, extracellular part to
which the hormone can bind and an intracellular part to which the G protein can
be coupled.
G-protein interaction with Carboxy terminus 3rd intracellular loop.
When a protein hormone binds to its receptor, GDP is phosphorylated
to GTP. GTP leaves the receptor and binds to an effector enzyme
(adenylyl cyclase). Effector enzyme activated: second messenger cAMP
formed from ATP.
Another effector enzyme can be guanylyl cyclase which forms cGMP.
Different G-proteins:
• G-protein that activates effector enzyme (Gs)
• G-protein that inhibits effector enzyme (Gi)
Protein hormones
• Neurotransmitters: synthesized by neurons, released and
influences directly neighboring cells (nerve cell, muscle,
secretory cell)
o 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
Derived by steroids: lipids with 4 characteristic carbon ring structures.
Sex hormones and hormones of the adrenal cortex.
All steroid hormones are derived from cholesterol → can diffuse into the cell and all have an
intracellular receptor.
Mechanism of hormone secretion for steroid hormones is different from that of protein hormones.
Steroid hormones are lipid hormones and can exit cell by passive diffusion. Almost no storage of
hormones in the cell, some storage by fat droplets.
Speed of production is speed of delivery → Speed of production is controlled
Steroid hormones bind to intracellular receptor after diffusion into cell. This hormone-receptor
complex travels to nucleus where it is able to bind to binding domain in the promotor → results in
gene expression.
Steroid hormones are not able to dissolve in the watery plasma, but are coupled to transport
proteins to be able to circulate in the plasma. They are not cut into bioactive substances into the
plasma, but transported to the liver where they are sulphated or converted into glucuronic acid to
become bio inactive.
4
