Endocrinology
Lecture 1 – Introduction
Endocrinology: medical specialty and biological science that deals with the endocrine system or glands that have secretions in
the body e.g. thyroid gland, pituitary, and adrenal glands.
Endocrinologists: Doctors and biologist who specializes in endocrinology
History of endocrinology
First endocrine experiment (1849)
● Conclusion: testis produces something that conditions the blood
● This conditioned blood caused the changes in the male
● Years later: testosterone found as the hormone of the testis
Bayliss and starling: Secretin (1902)
● Cut down the innervation of the pancreas and duodenum
● Bicarbonate is still produced
● Suggests that something else is released from the duodenum
● Acid → secretin → bicarbonate
Discovery of insulin (1922)
● Removal of pancreas in dogs: diabetes like symptoms
● Role of islets of langerhans and isolation of insulin
Discovery of neurotransmitters (1921)
Discovery of the role of the hypothalamus and pituitary gland
● Regulation of the pituitary gland by the hypothalamus
● TRH (thyroid releasing hormone)
○ Sheep (guillemin)
○ Pig (schally)
● inhibiting/releasing hormones produced from the hypothalamus
Development new techniques
● RIA (radioimmunoassay) 1950: measuring hormone concentration in the plasma. Not used anymore, nowadays ELISA
is used
● Molecular biology
○ Genes hormones
○ Genes receptors
○ Overexpression and knockout hormones/receptors
Endocrine system
Endocrine cell in eg pituitary gland → releases hormone in bloodstream → acts on either testis or ovary
Exocrine gland: delivery products to a duct that leads to the lumen of another organ, eg intestines. Products do not enter the
bloodstream. The rest of the pancreas produces all kinds of factors and is released into ducts and enter intestines to help with
food absorption. Usually the exocrine factors should not come into contact with living cells of the body therefore why ducts are
used.
Hormone release
● Endocrine: tissue that makes and releases hormones that travel in the bloodstream and control the actions of other
cells or organs.
● Neuroendocrine: neuronal cell releases hormones into circulation
● Paracrine: cell that releases factors into the extracellular space affecting the neighbouring cells
● Autocrine: cells releases factor into intracellular space affecting the same cell
● Neurocrine: releasing factors
,2 intercellular communication systems that control physiology:
● Nervous system
● Endocrine system
Homeostasis: regulation and maintenance of a balance, so that the state of the
intestinal environment in the body (blood and tissue fluids) remains stable
● As soon as a certain value (eg blood glucose level or body temperature)
deviates from the norm
● Almost all endocrine systems work through this negative feedback
● Target Tissue releases metabolites or hormones, sensed by endocrine
tissue, then that is negative feedback
Negative feedback: dietary intake → glucose increased → pancreatic b cells
increases insulin → liver produces more glycogen → blood glucose decreases
Homeostasis – negative feedback 2 hormone systems
● Decreased metabolism → endocrine tissue A produces hormone A → target
tissue product
● Example:
○ eat calcium, increased blood calcium → thyroid senses it →
calcitonin released by thyroid follicles → calcium taken up in the
bones
○ Decreased blood calcium → parathyroid glands release
parathormone → calcium is released from the bones into circulation
Positive feedback system
● One metabolite or hormone further increases the release of the same hormone
● Estrogen increased ←→ FSH/LH increased
Hormone categories
I. Protein hormones
○ Amino acids
○ 3-180 AA
○ linear/ring structure
○ Linear: double/single chain
○ monomer/dimer
○ Special adaptations
■ Sulfation of tyrosine
■ Glutamate pyrrole structure
■ Carbs (glycoproteins)
○ Isoforms (gene level/transcription level)
○ Hydrophil: cannot diffuse inside the cell (extracellular receptors)
○ Synthesis of protein hormones
■ DNA-transcription/mRNA translation and formation of hormone
■ Preprohormone(ER) → prohormone (golgi apparatus) →
hormone (packed into secretory granules remaining in the cell
and released into nucleus in case of signal)
Hormone secretion: protein hormones
● Stimulus → intracellular ca2+ → fusion of secretory granules with cell membrane →
exocytosis
● Release of hormones is not dependent on the translation → it can be immediate
,Hormone circulation and metabolism
● Protein hormones: broken down into inactive metabolites → usually short
half life.
● Quick process
Mechanism of hormone effects
● A receptor only binds 1 specific hormones (ligand binding specificity)
● but there could be different isoforms of receptors which induce different cell
responses
○ Receptor agonist: binds to receptor, mimics a hormone
○ Receptor antagonist: occupies a receptor, and prevents activation of the receptor by the hormone
Plasma membrane receptors/extracellular receptors
● All protein hormones are extracellular receptors
a. Channel bound receptor
b. Enzyme linked receptors/enzyme receptor
c. G protein coupled receptor
■ Span through the cell membrane
■ 7 spannings
■ Outside: NH2 tail → hormone can bind
■ Inside: COOH → receptor bound to g protein (alpha & beta subunit
bound to GDP)
■ Upon activation, GDP becomes GTP → adenylyl cyclase converts ATP →
cAMP → cyclic AMP dependent protein kinase A →
protein phosphorylation
Different protein hormones
● Insulin glucagon, growth hormone, ACTH, TSH etc
● Neurotransmitters: synthesized by neurons released and influenced
directly by neighboring cells (nerve cell, muscle, secretory cell)
○ Neurotransmitters as hormone: dopamine
● Neuropeptides: peptide hormones produced by nerve cell (oxytocin,
CRH, GnRH)
● Growth factors: peptide hormones that regulate growth activity (NGF,
TGF-b, EGF)
II. Steroid hormones
● Steroids: lipids with 4 characteristic carbon ring structures
○ Sex hormones: testosterone, estradiol, progesterone
○ Hormones of the adrenal cortex: cortisol corticosterone, aldosterone
● Derived from cholesterol → diffuse into the cell → intracellular receptor
● Unlike how protein hormones are stored inside vesicles of the cell, steroid hormones almost have no storage
in cell, minimal fat droplets
● Exit cell by passive diffusion
● Speed of production is speed of delivery
● Speed of production is controlled
● Not immediate release
● It is not as quick as the protein hormones
Mechanisms of hormone effects
Steroid hormone A → hormone-receptor complex → diffuses into nucleus → binding domain promoter → gene
expression
Steroid hormone circulation and metabolism
● Coupled to transport proteins
● Inactivated by the liver
, ○ Liver: sulphation of steroid hormones
○ Liver: glucuronic acid conversion
Steroid vs protein hormones
steroid protein
Intracellular receptor Extracellular receptor
Speed of production is speed of delivery to the circulation, Release of hormones is not dependent on the translation →
Slower delivery into the circulation it can be immediate
Longer half life, inactivated in the liver
Bound to binding proteins
Hormone categories
III. Amines: hormones made from tryptophan or tyrosine
○ Melatonin: tryptophan
○ Catecholamines: 1 tyrosine
○ Thyroid hormone: 2 tyrosines
■ Unique hormone: iodine needed for its functioning
■ Just like steroid; needs intracellular signaling
Bonus hormone categories:
● Eicosanoids and fatty acid derivatives: prostaglandins, thromboxanes, leukotrienes
● Pheromones: organic structures with carbon and hydrogen atoms. Is released by an animal and causes a behavioral
change in another animal.
● Electrolytes and metabolites: “hormone action”
○ Na+: binds to osmoreceptors
Mechanisms of hormone effects
● A cell can only respond to a hormone if the cell has the receptor for that hormone
● A cell does not contain all receptors for all hormones
● But multiple types of cells can contain the same receptor
● The amount of receptors that a cell contains determines response to a hormone
Hormone effects
● Hormone a
○ Target has no receptor: no response
○ Target has receptor: response a
○ Target has receptor A and B: receiving hormone B → response B
● Many effects according to different receptors present
Endocrinology and homeostasis
● Individual physiology is influenced by endocrine system, which in turn is affected by external/environmental factors
and internal factors
● Temperature, length of day, odors, pain, changed electrolyte concentrations
● Body must react to these changes
● Endocrine system does so by producing hormones, thereby inducing homeostasis
● Interactions between nervous system and endocrine system
Lecture 1 – Introduction
Endocrinology: medical specialty and biological science that deals with the endocrine system or glands that have secretions in
the body e.g. thyroid gland, pituitary, and adrenal glands.
Endocrinologists: Doctors and biologist who specializes in endocrinology
History of endocrinology
First endocrine experiment (1849)
● Conclusion: testis produces something that conditions the blood
● This conditioned blood caused the changes in the male
● Years later: testosterone found as the hormone of the testis
Bayliss and starling: Secretin (1902)
● Cut down the innervation of the pancreas and duodenum
● Bicarbonate is still produced
● Suggests that something else is released from the duodenum
● Acid → secretin → bicarbonate
Discovery of insulin (1922)
● Removal of pancreas in dogs: diabetes like symptoms
● Role of islets of langerhans and isolation of insulin
Discovery of neurotransmitters (1921)
Discovery of the role of the hypothalamus and pituitary gland
● Regulation of the pituitary gland by the hypothalamus
● TRH (thyroid releasing hormone)
○ Sheep (guillemin)
○ Pig (schally)
● inhibiting/releasing hormones produced from the hypothalamus
Development new techniques
● RIA (radioimmunoassay) 1950: measuring hormone concentration in the plasma. Not used anymore, nowadays ELISA
is used
● Molecular biology
○ Genes hormones
○ Genes receptors
○ Overexpression and knockout hormones/receptors
Endocrine system
Endocrine cell in eg pituitary gland → releases hormone in bloodstream → acts on either testis or ovary
Exocrine gland: delivery products to a duct that leads to the lumen of another organ, eg intestines. Products do not enter the
bloodstream. The rest of the pancreas produces all kinds of factors and is released into ducts and enter intestines to help with
food absorption. Usually the exocrine factors should not come into contact with living cells of the body therefore why ducts are
used.
Hormone release
● Endocrine: tissue that makes and releases hormones that travel in the bloodstream and control the actions of other
cells or organs.
● Neuroendocrine: neuronal cell releases hormones into circulation
● Paracrine: cell that releases factors into the extracellular space affecting the neighbouring cells
● Autocrine: cells releases factor into intracellular space affecting the same cell
● Neurocrine: releasing factors
,2 intercellular communication systems that control physiology:
● Nervous system
● Endocrine system
Homeostasis: regulation and maintenance of a balance, so that the state of the
intestinal environment in the body (blood and tissue fluids) remains stable
● As soon as a certain value (eg blood glucose level or body temperature)
deviates from the norm
● Almost all endocrine systems work through this negative feedback
● Target Tissue releases metabolites or hormones, sensed by endocrine
tissue, then that is negative feedback
Negative feedback: dietary intake → glucose increased → pancreatic b cells
increases insulin → liver produces more glycogen → blood glucose decreases
Homeostasis – negative feedback 2 hormone systems
● Decreased metabolism → endocrine tissue A produces hormone A → target
tissue product
● Example:
○ eat calcium, increased blood calcium → thyroid senses it →
calcitonin released by thyroid follicles → calcium taken up in the
bones
○ Decreased blood calcium → parathyroid glands release
parathormone → calcium is released from the bones into circulation
Positive feedback system
● One metabolite or hormone further increases the release of the same hormone
● Estrogen increased ←→ FSH/LH increased
Hormone categories
I. Protein hormones
○ Amino acids
○ 3-180 AA
○ linear/ring structure
○ Linear: double/single chain
○ monomer/dimer
○ Special adaptations
■ Sulfation of tyrosine
■ Glutamate pyrrole structure
■ Carbs (glycoproteins)
○ Isoforms (gene level/transcription level)
○ Hydrophil: cannot diffuse inside the cell (extracellular receptors)
○ Synthesis of protein hormones
■ DNA-transcription/mRNA translation and formation of hormone
■ Preprohormone(ER) → prohormone (golgi apparatus) →
hormone (packed into secretory granules remaining in the cell
and released into nucleus in case of signal)
Hormone secretion: protein hormones
● Stimulus → intracellular ca2+ → fusion of secretory granules with cell membrane →
exocytosis
● Release of hormones is not dependent on the translation → it can be immediate
,Hormone circulation and metabolism
● Protein hormones: broken down into inactive metabolites → usually short
half life.
● Quick process
Mechanism of hormone effects
● A receptor only binds 1 specific hormones (ligand binding specificity)
● but there could be different isoforms of receptors which induce different cell
responses
○ Receptor agonist: binds to receptor, mimics a hormone
○ Receptor antagonist: occupies a receptor, and prevents activation of the receptor by the hormone
Plasma membrane receptors/extracellular receptors
● All protein hormones are extracellular receptors
a. Channel bound receptor
b. Enzyme linked receptors/enzyme receptor
c. G protein coupled receptor
■ Span through the cell membrane
■ 7 spannings
■ Outside: NH2 tail → hormone can bind
■ Inside: COOH → receptor bound to g protein (alpha & beta subunit
bound to GDP)
■ Upon activation, GDP becomes GTP → adenylyl cyclase converts ATP →
cAMP → cyclic AMP dependent protein kinase A →
protein phosphorylation
Different protein hormones
● Insulin glucagon, growth hormone, ACTH, TSH etc
● Neurotransmitters: synthesized by neurons released and influenced
directly by neighboring cells (nerve cell, muscle, secretory cell)
○ Neurotransmitters as hormone: dopamine
● Neuropeptides: peptide hormones produced by nerve cell (oxytocin,
CRH, GnRH)
● Growth factors: peptide hormones that regulate growth activity (NGF,
TGF-b, EGF)
II. Steroid hormones
● Steroids: lipids with 4 characteristic carbon ring structures
○ Sex hormones: testosterone, estradiol, progesterone
○ Hormones of the adrenal cortex: cortisol corticosterone, aldosterone
● Derived from cholesterol → diffuse into the cell → intracellular receptor
● Unlike how protein hormones are stored inside vesicles of the cell, steroid hormones almost have no storage
in cell, minimal fat droplets
● Exit cell by passive diffusion
● Speed of production is speed of delivery
● Speed of production is controlled
● Not immediate release
● It is not as quick as the protein hormones
Mechanisms of hormone effects
Steroid hormone A → hormone-receptor complex → diffuses into nucleus → binding domain promoter → gene
expression
Steroid hormone circulation and metabolism
● Coupled to transport proteins
● Inactivated by the liver
, ○ Liver: sulphation of steroid hormones
○ Liver: glucuronic acid conversion
Steroid vs protein hormones
steroid protein
Intracellular receptor Extracellular receptor
Speed of production is speed of delivery to the circulation, Release of hormones is not dependent on the translation →
Slower delivery into the circulation it can be immediate
Longer half life, inactivated in the liver
Bound to binding proteins
Hormone categories
III. Amines: hormones made from tryptophan or tyrosine
○ Melatonin: tryptophan
○ Catecholamines: 1 tyrosine
○ Thyroid hormone: 2 tyrosines
■ Unique hormone: iodine needed for its functioning
■ Just like steroid; needs intracellular signaling
Bonus hormone categories:
● Eicosanoids and fatty acid derivatives: prostaglandins, thromboxanes, leukotrienes
● Pheromones: organic structures with carbon and hydrogen atoms. Is released by an animal and causes a behavioral
change in another animal.
● Electrolytes and metabolites: “hormone action”
○ Na+: binds to osmoreceptors
Mechanisms of hormone effects
● A cell can only respond to a hormone if the cell has the receptor for that hormone
● A cell does not contain all receptors for all hormones
● But multiple types of cells can contain the same receptor
● The amount of receptors that a cell contains determines response to a hormone
Hormone effects
● Hormone a
○ Target has no receptor: no response
○ Target has receptor: response a
○ Target has receptor A and B: receiving hormone B → response B
● Many effects according to different receptors present
Endocrinology and homeostasis
● Individual physiology is influenced by endocrine system, which in turn is affected by external/environmental factors
and internal factors
● Temperature, length of day, odors, pain, changed electrolyte concentrations
● Body must react to these changes
● Endocrine system does so by producing hormones, thereby inducing homeostasis
● Interactions between nervous system and endocrine system
