Powerpoint 1 Flashcards
Modern vs. Classical definition of hormone
Classical: Chemical messenger released by 1 type of cells and carried in bloodstream to act on specific target cells.
Modern: Includes factors produced and used locally without entering the blood stream
What is endocrinology about?
communication between cells - multicellular organisms have to communicate
What 3 aspects is endocrinology required for?
- Development form the fertilized egg to the adult organism (differentiation)
- Maintenance of the envr. in which cells can live (homeostasis)
- reproduction
Number of cells in human adult vs number of people in entire population:
Cells in human adult: 10^14
^ about 10,000 times the entire population
How many protein incoming genes coordinate all of the cells in the human body? How is this coordination achieved?
21,000 via networking (gene interaction)
What are the 3 layers of signalling networks?
- within cells
- between groups of cells (tissues)
- between tissues (organs?)
Life evolved about ________ years ago, but multicellular organisms evolves less than ________ years ago.
3.8 billion
600 million
Shows how complex these networks are
What are recipient cells?
Cells that recognize hormone signals and respond to them.
Recipient cells are exposed to many signals at the same time, therefore they response is:
an integrated response to all these signals
What are the two main control systems of the body and what is the difference between the two?
Together, what are they responsible for?
Nervous system - there is a direct connection between organs concerned.
Endocrine system - sending chemical messages (hormones) into the circulation (radio station)
Monitoring internal and external environments and making adaptive changes (homeostasis)
Out of the endocrine and nervous system, which is slower?
Endocrine is much slower because signals must be translocated and diffused
Endocrine cells:
Secrete HORMONES into blood vessels. Target cells may be distant
Paracrine cells:
Secrete HORMONES which act locally on neighbouring cells
Autocrine cells:
Secrete HORMONES which acts on themselves or on identical neighbouring cells
Neuroendocrine cells:
Secrete MOLECULES from axon terminals into the blood stream
Neurotransmitter cells:
Secrete MOLECULES from axon terminals to activate adjacent neurons
What are 2 general characteristics of hormones?
- Very low in concentration (ng/ml) or (pg/ml)
2. Very specific receptor (1 hormone, 1 receptor)
What 5 type of molecules can a hormone be?
- peptides (3 to >180 aa)
- modified aa
- cholesterol based (steroid)
- synthesized from FAs (prostaglandins)
- gases (nitric oxide)
Where might cells that synthesize hormones be located?
- clustered in endocrine glands
2. interspersed as single cells in organs
What are the 3 main classes of hormone - give examples of each?
- Lipid: steroids, eicosanoids
- Proteins: short polypeptides, large proteins
- AA derivatives
Lipid hormones: Steroids
Derivative of what?
Size of molecule?
Source?
Found where?
- cholesterol
- large (hydrocarbon ring)
- diet, de novo synthesis
- cell membrane
Chemical vs. 3D structure of testosterone and estrogen
Chemically very similar
3D structure differs markedly
What two endocrine glands are steroid hormones produced in?
Adrenal glands and Gonads (testis and ovaries)
What two types of molecules do adrenal glands secret and what do each affect?
- Mineralocorticoids: affect mineral homeostasis
2. Glucocorticoids: Affect glucose metabolism and immune function
What 3 type of molecules do Gonads (testes and ovaries) secrete?
- estrogen
- progestin/progestagens
- androgens
What are 4 examples of Eicosanoids?
Prostaglandins
Thromboxanes, leukotrienes, prostacyclins
What are two characteristics of prostaglandins?
- inflammatory reaction
2. reproduction
Prostaglandins and related compounds are collectively known as ____________.
Eicosanoids
What are eicosanoids produced from?
arachidonic acid
What is arachidonic acid characterized as?
a 20-C polyunsaturated fatty acid (5,8,11,14-eicosatetraenoic acid)
What molecule is a good example of a prostaglandin?
PGH2 (prostaglandin H2)
What are the two major pathways of eicosanoid metablolism? (draw it out)
Linear and Cyclic
What enzyme catalyzes the “committed step” in the cyclic pathway of eicosanoid metabolism?
PGH2 synthase
What are 2 characteristics of the products produced from the cyclic pathway of eicosanoid metabolism?
- They have specific effects on target cells close to their site of formation.
- There are rapidly degraded, so they are not transported to distal sites within the body
What are 3 examples of neurohormones? How many amino acids do each contain?
- GnRH (10)
- Oxytocin (9)
- TRH (3)
- What is the hormone arginine vasopressin associated with?
- What is the hormone Oxytocin associated with?
How do these hormones differ?
- Vasoconstriction/water retention
- milk ejection/labour
Differ in aa #3 and #8. Very small differences profoundly affect physiological effects
What are 3 characteristics of large polypeptide protein hormones?
- linear chain
- subunits are linked by disulphide bridges
- 3D structure is critical for interaction with receptor
(everything folds into its minimal energetic form)
What two locations in the body produce hormones from tyrosine? What hormones are produced from tyrosine here?
- Thyroids: thyroxine (T4) and triiodothyronine (T3)
2. Adrenal medulla: epinephrine, norepinephrine, dopamine
Tyrosine metabolite hormones produced from the adrenal medulla are often used as what?
neurotransmitters
What are 3 characteristics of the composition on endocrine glands?
- Parenchyma (mass of secretory cells)
- Highly vascularized blood vessels
- no ducts
What two types of cells produce hormones?
- specialized secretory
2. neurons
In what 3 locations can you find cells that produce neuronal hormones?
- hypothalamus
- posterior pituitary
- adrenal medulla
Where are storage peptide hormones stored?
secretory vesicles (granules) in cytoplasm
How are peptide hormones stored in granules moved to the cell membrane?
microtubules (cytoskeleton) and microfilaments
What do cells require in order to activate and release a stored pro hormone?
stimulus - may be a hormonal stimulus
What do stimuluses that activate and release stored hormones from granules normally change in cells?
Ca2+ permeability of the cell membrane (opening of Ca channels)
What is the major difference between the synthesis of peptide hormones and steroid hormones?
Peptide hormones are stored in granules and released out of cell instantaneously upon receiving stimulus. They are pre-made, stored, and waiting to be released.
Steroid hormones must be CREATED and then released.
Where are cholesterol molecules stored? What are they stored as?
- cytosol
2. cholesterol esters in lipid droplets
What is the progression of the formation of a cholesterol molecule from its storage in lipid droplets to its exit from the cell?
Cholesterol esters from lipid droplets in cytosol move into mitochondria where they are converted to pregnenolone. They are then transported to the smooth ER and transformed into the appropriate hormone. They then exit cell
Is there storage of steroid hormones in cells?
no
What type of hormones are hydrophilic and can circulate freely in blood?
peptide and protein hormones
What are two examples of hormones that are more hydrophobic and require carrier proteins?
thyroxin, steroid hormones
What are two examples of hormone transport molecules (binding proteins) in blood?
- thyroxin globulin
2. cortisol binding protein
How do binding proteins act as a buffer in the blood?
By transporting the hormone and protecting it from degradation in the liver
When is a hormone biologically active / not?
active: free form
not-active: bound to transport molecule - it must dissociate from binding protein in order to bind to receptor
Do peptide hormones of large protein hormones have a larger half life in circulation?
large protein hormones
The blood concentration of what 3 substances controls synthesis and secretion of hormones?
- Ca
- Glucose
- Water
Endocrine disorders: what does a lack of GH cause in:
- Children
- Adults
- dwarfism
2. atrophy of muscle tissue
Endocrine disorders: what disease does a lack of cortisol and aldosterone cause? What is the mechanism?
Addison disease. Lack of hormone increases ACTH secretion by the pituitary (removes negative feedback). Co-secreted melanocyte stimulating hormone also increases. Leads to excessive freckling.
What is the most common endocrine disorder? Due to what?
Diabetes mellitus. May be due to lack of secretion of insulin from the beta-cells of the cells of Langerhans in the pancreas. Can also be caused by a receptor defect (does not respond to insulin administration)
What is a 24 hour endocrine rhythm cycle called?
circadian rhythm
What are endocrine rhythm cycles called that are longer than 24 hours? 1 example?
infradian rhythm
ex: 28 day menstrual cycle
What are 2 examples of circadian rhythms?
- cortisol secretion: maximal between 4-8 am
2. Gh and PRL: maximal 1 hr after going to sleep
What is the difference in the release time of gonadotrophin during puberty vs adult?
Puberty: mainly at night
Adults: pulsatile fashion (burst-like – not constant over time)
What must be taken into account while measuring hormone levels?
Rhythms
What do bioassays measure?
response of animal or cell to a hormone
How did human pregnancy use to be determined between 1930 - 1950s?
THE RABBIT TEST: hCG is produced by placenta 8 days after fertilization. Urine injected into rabbit and if hCG was present, then the rabbits ovaries would ovulate and form corpora lutea. The rabbit would then be killed to determine pregnancy (+/- corpora lutea)
2 cons of bioassays?
- time consuming
2. do not accurately measure levels of hormone
Radioimmunoassays (RIA) work off of what principle?
competitive binding of anybody to its antigen
How do enzymoimmunoassays (EIA) differ from RIAs?
What is an example of an enzymoimmunoassay?
What is a similar technique called?
ALSO work on the principle of competitive binding of an antibody to its antigen BUT EIAs do not require radioactive tags. Rather, the antibody the antibody is tagged with a compound that changes colour in response to binding with the antigen.
Ex. home pregnancy test
Enzyme-linked immunosorbent assay (ELISA)
RIAs and EIAs can be used on _______ and/or ______ samples depending on the hormone
- blood
2. urine
What are 3 other common endocrinology techniques (+ examples)?
- Indirect measurements of hormone levels. Ex: blood glucose levels are more useful than insulin levels to diagnose/treat diabetes mellitus
- Proactive and Suppression tests. In some hormones, it is easier to assess the status by maximally stimulating or suppressing hormone release and comparing the result average healthy individuals. This is especially useful with hormones that are fluctuating normally during the day, therefore fewer blood/urine samples required
- Imaging studies - magnetic resonance imaging (MRI) and computer tomography (CT) - allows visualization of endocrine glands and perhaps tumours
What two systems are used in gene editing?
CRISPR
Cas9
Collect autologous cells from patient and modify it in vitro to correct lesion the re-introduce to patient
