1 Flashcards
Define a hormone
Chemical messenger released by one type of cells and carried in the bloodstream to act on specific target cells
Includes factors produced and used locally without entering the blood stream
Do hormones always travel a long distance?
no
Do endocrine organs have ducts?
NO, only exocrine
What is endocrine communication required for?
- Development from the fertilized egg to the adult
organism (differentiation) - Maintenance of the environment in which cells can live (homeostasis)
- Reproduction
How is coordination of cells achieved?
by networking aka gene interaction
What are the layers of signalling networks?
- Within cells-> intracellular
- Between groups of cells (tissues)-> extracellular
- Between tissues-> intertissue
Does a change in network necessarily affects the outcome?
negative or positive response can occur, according to a response
less of one connection will probably not affect the final output due to redundancy and compensatory mechanisms
Where are signals that participate in cell to cell communication are generated?
Signals are generated in special cells (hormone producing cells).
Main Control Systems of the Body
- Nervous system: Direct connection between organs concerned (fixed line telephone)
vEndocrine system: Sending chemical messages (hormones) into the circulation (radio station) - Responsible for monitoring internal and external environments and making adaptive changes (Homeostasis)
Name 5 classes of signals
Endocrine
Paracrine- signalling that affects nearby cells
Autocrine - a cell producing an effect on itself
Neuroendocrine- A type of cell signaling involving the release of a hormone from a nerve cell that has an effect on another cell.
Neurocrine
Describe endocrine signals
cells produce chemical signals, excrete them to circulation and the signals travel far away
Describe paracrine signals
cells produce chemical signals which diffuse WITHIN the tissue and affect other cells
Describe autocrine signals
signals are secreted by the cells and the cells themselves have the receptors, thus thy affect themselves
e.g. testes produce testosterone. Testostosterone affects testes
Describe neuroendocrine signals
hormones produced by neurones
e.g. epinephrin
any production from adrenal medulla is neuroendocrine
Describe neurocrine signals
hormones produced by neurones and released in the signalling cleft
IGF-1 is produced by almost all tissues but the main source is the liver
When produced by the liver, it can affect the cells that also make IGF-1
Describe concentrations of hormones
Very low in concentration
ng/ml) or (pg/ml
what are the possible types of structure of hormones
Can be peptides (3 to > 180 aa), modified aa, cholesterol based (steroids), synthesized from fatty acids (prostaglandins) or gases (nitric oxide)
Describe receptors for hormones
Very specific receptor
One hormone, one receptor
Membrane bound receptors
What are the 3 types of major responses to a hormone and their target proteins
- altered metabolism (via a metabolic enzyme)
- altered gene expression (via a gene regulatory protein)
- altered cells or shape movement (via a cytoskeletal protein)
What are the possible type of response of a cell to a signal
survival
division
differentiation
death
What happens when signalling stops completely?
death
What are the 3 main classes of chemical nature of hormones
lipids
proteins
Amino acid derivatives
What are the subclasses of lipid hormones
steroids
eicosanoids
What are the subclasses of protein hormones
Short polypeptides
Large proteins
Where are steroids found?
cell membrane
Are steroid hormones hydrophilic or hydrophobic
Highly hydrophobic
What is the structure of steroid hormones
hydrocarbon ring
All cholesterol derivatives contain __
All cholesterol derivatives contain sterol ring
Name 2 main types of steroid hormones
- Sex steroids
* Adrenal steroids
What are the subgroups of adrenal steroid hormones
• Mineralocorticoids
– Affect mineral homeostasis
• Glucocorticoids
– Affect glucose metabolism and immune function
What are the subgroups of sex steroid hormones
- Estrogens
- Progestogens
- Androgens
What is the precursor of eicosanoids
arachidonic acid (20C)
What are eicosanoids
metabolites of 20C fatty acid
Prostaglandins
Thromboxanes, leukotrienes, and prostacyclins
Describe prostaglandins
Produced by numerous tissues and organs
• Originally isolated from prostate gland secretion
• Inflammatory reaction
• Reproduction
Give example of short chain AA hormones
Neurohormones:
- GnRH (10)
- Oxytocin (9)
- TRH (3)
Give examples of peptide hormones
Vasopressin
Oxytocin
Describe peptide hormones
• Large polypeptides • Linear chain • Subunits - Linked by disulfide bridge(s) • 3-D structure - Critical for interaction with receptor
Name amino acid hormones
Tyrosine metabolites – Thyroid hormones • Thyroxine (T4) • Triiodothyronine (T3) – Adrenal medulla • Epinephrine • Norepinephrine • Dopamine • Often used as neurotransmitters
How can hormone producing cells be found in the body?
Cells that synthesize hormones may be clustered in endocrine glands
or
be interspersed as single cells in organs
Describe the arrangement of hypothalamus
hypothalamus is diffused structure
does’t have cells clumped together
Describe the composition of endocrine glands
– Parenchyma (mass of cells) • Secretory cells – Blood vessels • Highly vascularized – No ducts
How long do endocrine glands persist in the body?
Permanent or transient
– Pituitary, adrenal, pancreas are permanent
– Ovarian follicle and corpus luteum are transient
Transient vs permanent glands
transient endocrine organs are typically needed for reproduction
some organs can become an endocrine organ for a period of time e.g. endometrium
What are the 2 types of cells that produce hormones?
1) Specialized secretory cells - Usually one type of cells
produce one hormone
2) Neurons
Name neural cells that produce hormones
– Hypothalamus
– Posterior pituitary
– Adrenal medulla
What has to occur in order for protein hormones to become functional?
hormone becomes functional only after post-translational modifications
WHat are physical/chemical modifications that occur to protein hormones?
- Cleaving of long amino acid chain (preprohormones) to generate small peptide hormones (GnRH, oxytocin, TRH)
- Interaction and linking of subunits • 3-D structure
What is the initial form of protein hormones
preprohotmone
Name 3 types of modifications that occur to mRNA during it’s synthesis?
5’- capping
splicing
poly-A-tai
What are the post-translational modifications that occur with preprohormone?
1) Cleavage of signal peptide-> pro-hormone is formed- 1 step that occurs to all of hormones
Other possible modifications:
2) Sulphide bonds are created which can help in protein folding -> 3D strucutre
3) Cleavage of terminal portion of the protein which occurs at the amino terminal
4)a signal long protien is made and it is then cleaved into differently sized peptides, and only those, that are needed by the cells are kept, the rest are broken down.
5) a protein is made, and cleaved in such a way that small potion is thrown out and the other portions are reoriented.
The parts are connected with sulphide bonds- insulin is made in this manner
6) 2 subunits are expressed by 2 different genes. The hormones that result from this post-translation modification are made out of alpha and beta chains which are made by different genes.
Trophic hormones are processed in such way
Describe the process of glucagon formation and associated processes
Glucogon. It is expressed as proglucagon which is very long and complex.
After it is translated, only small portion of it is kept, the rest is destroyed. This occurs in alpha pancreatic cells
Another possibility- the other part of that peptide is kept and glucagon is formed-> GLP (glucagon like peptide) is formed
Thus there are multiple different proteins produced by 1 gene
WHat is the enzyme that cleaves the signal peptide
Lipophilic leader sequence (signal peptide) is cleaved by peptidase.
Where are sulphide bonds formed?
between cysteines
Which peptides become glycosylated?
Most of them, especially the long ones
How are proteins transported across cell membranes?
By vesicles (or granules) made in golgi
What occurs in vesicles?
Further glycosylation and proteolytic cleavage
How are protein hormones released?
by exocytosis
Movement to the cell membrane mediated by microtubules (cytoskeleton) and microfilament.
Cells require a stimulus to activate and release the stored prohormone- typically, it involves Ca2+ which acts as a signalling trigger to initiate exocytosis
What else can be contained in vesicles, apart from hormones
Sometimes proteins are packed in vesicles with activating peptidase
peptidases activate only after hormones are released
Cleave prohormone into hormones by cutting off the singling sequence
Can protein hormones be stored?
Yes, in vesicles
Differences between cells that produce peptide hormones vs steroid hormones
there is more RER in peptide making cells because thats where translation occurs- ribosomes are required as they are the site of protein translation
The more protein is produced, the more ribosomes are there in the cell
steroid producing cells need more SES where steroid making process occurs
Describe the steps of sterol hormone synthesis
It is an enzymatic process with cholesterol being the precursor for all the hormones
1) Cholesterol is transported into the mitochondria and converted to pregnenolone via the cleavage of the side chain
2) Pregnenolone is a common precursor for all steroid hormones. It is then transported from mitochondria to SER to be converted into progesterone
3) Progesterone is then converted into glucocorticoids (e.g. cortisol), mineralocorticoids (e.g. corticosterone), testosterone depending on the cell type
What is the precursor for estradiol?
testosterone
What is the precursor for aldosterone?
corticosterone
Where is cholesterol stored
Cholesterol molecules are stored in the cytosol as cholesteryl esters in lipid droplets
When is cholesterol moved to mitochondria for sterol hormone production
after a signal is received
Are steroid hormones be stored?
no, they are lipid soluble- will simply diffuse out of the membrane
Can stereogenic cells make their own cholesterol?
yes
How are steroid hormones released?
by diffusion
how are hydrophilic hormones transported in blood?
Hydrophilic molecules (protein hormones and catecholamines) can circulate in a free state
how are hydrophobic hormones transported in blood?
hydrophobic hormones (thyroxin, steroid hormones) require carrier proteins that are specific for the particular hormone
Give examples of carrier proteins for hydrophobic hormones
thyroxin binding globulin, cortisol-binding globulin etc.
What is the effect of binding proteins on hormones?
Binding proteins act as a buffer influencing their half-life and bioavailability
How is length of hormones related to their half-life?
short hormones have short half life
long have long due to translational modifications such as glycosylation. various levels of glycosylation can occur. The more the glycosylation, the longer the half life
How are peptides degraded?
by proteolytic enzymes
What are levels of hormones present in the body dictated by?
levels of hormones are maintained at a levels that are required for body function
they are maintained through receiving signals
What are the various inputs that control hormonal levels (3)
- neural inputs: brain and hypothalamus
- Hormonal stimulation/inhibition – Releasing factors/hormones
– Inhibitory factors
– Feedback system - Metabolic status:
– Stress
– Blood concentrations of substances
• Ca
• Glucose
• Water
Describe general 2 hormone feedback systems
if there are more than 2 endocrine organs in regulatory chain
e.g. hypothalamus pituitary adrenal axis system
- more than 2 endocrine organs in regulatory chain e.g. hypothalamus pituitary adrenal axis system
- Hormone A produced by endocrine tissue A has a positive feedback effect on target tissue, which in turn has a stimulatory effect on endocrine tissue B
- Endocrine tissue B releases a hormone acts upon target tissue, resultign in an overall decreased function of endocrine tissue A
This target tissue can have its local PARACRINE signals
What are the types of endocrine disorders
- Overproduction
- Underproduction
- Altered tissue response- target tissue has problems, the production levels of hormone are normal
- Tumors of endocrine organ
- Excessive hormone metabolism- normal production levels and the target organ machinery works fine, but the hormone metabolism is weird
Which organs metabolize hormones?
the hormones are metabolized in liver and kidney (also in lungs). If the metabolism in these organs is affected, the half life is either extended or shortened
Describe lack of GH disorder
lack of growth hormone
– Children: Dwarfism
– Adults: Atrophy of muscle tissue etc.
Describe lack of cortisol and aldosterone (adrenal gland)
Addison disease
Lack of hormones increases ACTH secretion by the pituitary- Adrenocorticotropic hormone (ACTH) is a hormone produced in the anterior, or front, pituitary gland in the brain. The function of ACTH is to regulate levels of the steroid hormone cortisol, which released from the adrenal gland.
Co-secreted melanocyte stimulating hormone also increases-> high melatonin level
Leads to bronzing (darkening).
Describe steroid hormones disorders
Defective enzymes in the path of synthesis.
– Additional problems from the accumulation of intermediates
What is the most common endocrine disorder
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 are the factors that contribute to hormonal rhythmicity
hormones have endogenous rhythmicity or rhythmicity that comes from external factors
What is hormonal rhythmicity usually inflicted by?
light-dark cycles
What is the source of endogenous rhythmicity?
Signal from the brain independent of external cues
What are circadian rhythms
Rhythms that occur during 24-h period
also known as circadian rhythm
WHat is the regulators of circadian rhythm
mostly hypothalamus but individual organs can also contribute it
Which organs can responds to light-dark signals?
hypothalamus only
What is an infradian rhythm?
infradian rhythm is a rhythm with a period longer than the period of a circadian rhythm, i.e. with a frequency less than one cycle in 28 hours, such as menstruation, breeding, tidal or seasonal rhythms. In contrast, ultradian rhythms have periods shorter than the period of a circadian rhythm.
What is the rhythm of cortisol?
Cortisol secretion: maximal
between 4-8 a.m.
What are the rhythms of GH and PRL?
GH, PRL maximal secretion 1h after going to sleep
Give an example of a rhythm that changes during development?
Gonadotrophin: Released mainly at night during puberty. Released in a pulsatile fashion in adults.
Rhythms have to be taken into account when measuring __
Rhythms have to be taken into account when measuring hormone levels
