What does hormone mean in greek
Classical and modern definition of hormones
I excite, I arouse
Chemical messenger released by one type of cells and carried in the bloodstream to act on specific target cellls. Includes factors produced and used locally without entering the blood stream
Who is father of endocrinology
Ernest Starling
Why communication between cells is required
- development from the fertilzed egg to the adult organism (differentiation)
- Maintenance of the environment in which cells can live (homeostasis)
- Reproduction
In multicellular organisms cells have to communicate
3 layers of signaling networks
Within the cells (intracellular)
Between groups of cells (tissues) intercellular
Between tissues (intertissual)
What process opposes networks change?
Homeostasis
How old is the earth
when life evolved
when multicellular organisms evovled
earth-4.5 billion years
life-3.8 billion years
Multicellular- 600 million
Main control systems of the body
Nerbous system (direct connection between organs concerned)
Endocrine system (sending chemcial messages hoemones into circulation)
Different types of cells producing signals
Neuroendocrine- epinephrine form medulla
In what concentrations hormones are usually present and they can be made of
- Very low in concentration
- (ng/ml) or (pg/ml)
-Can be peptides (3 to > 180 aa), modified aa,
cholesterol based (steroids), synthesized from fatty
acids (prostaglandins) or gases (nitric oxide)
How many receptors each hormone has
only 1
decribe general pathway of cellular repsonse to a hormone for membrane bound receptor
-Recognition of
signal by receptor
-Change of
intracellular
network of proteins
-Activation of
target genes or
proteins
-Cellular response
What chemical nature anad their subclasses hormones can be
1) Lipids
-Steroids
-Eicosanoids
2) Proteins
-Short polypeptides
-Large proteins:
Chemical modification through glycosylation
3) Amino acid derivatives
What response a hormone can induce in general
Metabolic enzyme (activation/inactivation)->altered metabolism
Gene regulatory protein->altered gene expression
Cytoskeletal protein->altered cell shape or movement
What usual signals cell receive and when it willundergo programmed death
Basic ABC signals are always there
Derivatives of cholesterol: what structure they have, what properties, source and where found in cell
– Large molecule
• Hydrocarbon ring
oh group
hydrocarbon tail
– Highly hydrophobic
– Source
• Diet
• De Novo synthesis
– Found in cell membrane
derivatives of cholesterol and what characteristic they share
– Vitamin D
– Bile acid
• Lipid digestion
– Steroid hormones
• Sex steroids
• Adrenal steroids
– All cholesterol
derivatives contain
sterol ring
Do male and female sex hormones look alike?
Testosterone and estradiol have chemically very similar formula
The difference is in functional group and methyl group
But structurally 2 hormones are vey different
Steroid hormones classes and subclasses and what do they do
-Adrenal
• Mineralocorticoids
– Affect mineral homeostasis
• Glucocorticoids
– Affect glucose metabolism and
immune function
-Gonads (testis and ovaries)
• Estrogens
• Progestogens
• Androgens
Lipid hormones are metabolites of what acid
20 c fatty acid (arachidonic acid)
what chemicals can be produced from arachidonic acid and function
-Prostaglandins
– Produced by numerous
tissues and organs
• Originally isolated from
prostate gland secretion
• Inflammatory reaction
• Reproduction
Prostaglandinds and related compounds are collectively known as
Eicosanoids
IUPAC name for arachidonic acid
5,8,11,14-eicosatetraenoic acid
Example of SCAAs that serve as neurohormones
GnRH(10)
Oxytocin(9)
TRH(3)
Difference in structure and function of arginine vasopressin and oxytocin
vasopressin has 3-Phe and 8-Arg
Oxytocin 3-Ile, 8-Leu
Arginine vasopressin: Vasoconstriction/Water retention
Oxytocin: Milk ejection/Labor
Subunits in large hormones are linked by
Disulfide bridges insulin, growth hormone)
tyrosine metabolites
Thyroxine (T4)
Triiodothyronine (t3)
Adrenal medulla produces what AAs metabolites
Epinephrine
Norepinephrine
Dopamine
How cells producing hormones can be localized
Cells that synthesize hormones may be clustered in endocrine gland or be interspersed as single cells in organs
Endocrine gands composition
Parenchyma (mass of cells)
• Secretory cells
– Blood vessels
• Highly vascularized
– No ducts
Permanent or transsitient endocrine glands
Pituitary, adrenal, pancreas
– Ovarian follicle and corpus
luteum
where neurins produce hormones
– Hypothalamus
– Posterior pituitary
– Adrenal medulla
How protein hormones are synthesized
– Transcription
– Translation
– Physical/chemical modification
• Cleaving of long amino acid chain (preprohormones) to
generate small peptide hormones (GnRH, oxytocin, TRH)
• Interaction and linking of subunits
• 3-D structure
what part of DNA is coding proteins
exons
3 types of translational modifications that mRNA undergoes
poly A tail
Splicing
Capping
When hormones becomem functional?
Hormones are synthesized as prohormones and then they are made fully functional at post translational modifications
What happens the first thing to the protein after translation if its destiny to be hormone
Cleavage of signaling peptide and it becomes a prohormone
4 types of post translational modifications to a prohormone
1) disulphide bonds formation ( that will help in creating three-dimensional structure) and/or cleavage of amino-acid terminal pro-hormone sequence (growth hormone or parathyroid hormone)
2) along protein is synthesized in the beginning and then it is broken down into different parts and only the parts that are needed for the cell are going to be left. The rest are ging to be digested (glucagon from pro-glucagon gene in alpha cells. The same gene in other cells of intestine, the other portion of the gene is going to be retained->GLP
3) one portion is cut out and other portions are reoriented (insulin)
4) alpha and beta portions of the hormone are synthesized in different genes and then are brought together (tropin hormones)
Signal peptide are cleaved by ___
Peptidases
formation of disulfide bridges happens at what AAs
Cysteins
Where hormones can be stored
In vesicles or granules from Golgi complex
Movement of vesicles to the cell mebrane is performed by
Microtubules (cytoskeleton) and microfilament
What vesicles with prohormone might also have and what is required to release prohormone
Activating peptidases (active only when they are released from vesicles), makes a prohormone into active hormone
Signal is required to release a stored prohormone (exocytosis)- T and V SMEAR proteins with Ca release inducing exocytosis
How cells secreting protein hormones and steroid hormones are different
In steroid cells there are less rough ER and more smooth
Describe the process of steroid hormone synthesis
Cholesterol is transported to mitochondria and converted to pregnenolone. It is transported out of mitochondria into smooth ER, where it is converted to progesterone and then it can be processes further depending on the cell type
are steroid hormones stored
No
What hormones can freely circulate in blood
Protein hormones and catecholamines
Why steroid hormones are not stored
Because they are lipid soluble and they can pass through vesicles
Steroid hormones are transported by
Specific proteins for each hormones
Thyroxin binding globulin, etc.
Binding proteins act as a buffer influencing ____
half-life and bioavailability
Short protein hormones and peptides are degraed by __ aand thus they have __ life
Large protein hormones haave ___ life
Proteolytic enzymes
Short half-life
Longer half-life, because of extensive glycosylation
What can control synthesis ad secretion of hormones
=Neural inputs
– Brain
– Hypothalamus
= Hormonal stimulation/inhibition
– Releasing factors/hormones
– Inhibitory factors
– Feedback system
= Metabolic status
– Stress
– Blood concentrations of substances
• Ca
• Glucose
• Water
Explain general 2 hormone feedback system
Endocrine disorders classification
v Overproduction
v Underproduction
v Altered tissue response
v Tumors of endocrine organ
v Excessive hormone metabolism
Lack of GH will cause
– Children: Dwarfism
– Adults: Atrophy of muscle tissue etc.
Lack of cortisol and aldosterone will lead to ___ disease and what are the signs
Addison disease. Lack of hormones increases ACTH secretion
by the pituitary (removes –ve feedback). Co-secreted
melanocyte stimulating hormone also increases. Leads to
bronzing (darkening)
where hormones are usually metabolized
Liver, some of them in the lungs
What step in steroid hormone synthesis can lead to defective hormone
Any defective enzyme in the path synthesis will lead to accumulation of intermediates
2 types of rhythms that entraine the brain to regulate hormone release
24 hour cycle:circadian rhytgm
Longer cycles: infradian rhytm (28 day menstrual cycle)
When rhytms should be taken in account and when they can be change and example of circadian rhythms+hormones
Examples of circadian rhythms:
– Cortisol secretion: maximal
between 4-8 a.m.
– GH, PRL maximal secretion 1h
after going to sleep
v Rhythms may change during
development
– Gonadotrophin: Released
mainly at night during puberty.
Released in a pulsatile fashion
in adults.
v Rhythms have to be taken into
account when measuring hormone
levels
Circadian rhythm proteins are secreted where
In the liver ( getting signals from hypothalumus or hormone signal)
Hourses are seasonal animals because
They breed only in summer