Endocrine system Flashcards
Define the endocrine system
- tissues and cells capable of secreting and responding to hormones
- communication system
- the two components communicate via chemical messengers called hormones
Define neural
- functions mediated by electro-chemical conduction along nerves
Define endocrine
- functions are mediated by chemical messengers called “hormones”
- chemical mediators produced in one part of the body which act on a distant part (“remote control”)
Define hormone. They are:
- a chemical substance, formed in one organ or part of the body and carried in the blood to another organ or part to illicit a response
- depending on the specificity of their effects, hormones can alter the functional activity of just one organ or of various numbers of them (GnRH -one, vs T3 - several)
Hormones are: - regulators of physiologic events (e.g. increase body temp, metabolism, etc)
- effective in minute quantities
- synthesized by cells/ endocrine glands
- greek hormon, to rouse or set in motion
Define paracrine
- chemical mediators produced in one cell that acts on a neighbouring cells (“neighbourhood watch”)
Define autocrine
- chemical mediator produced in one cell and acts on that same cell (“self control”)
Nervous vs endocrine system:
1. physical form of information transfer
2. speed of information transfer
3. mechanism of gradation
4. mechanism to achieve specificity
Nervous:
1. action potentials
2. fractions of seconds
3. frequency
4. “wiring”
Endocrine:
1. chemicals
2. minutes, hours, days (varies)
3. amplitude modulation
4. receptors
What are the different hormone types?
- peptide/ polypeptide
- steroid
- amino acid derivatives
Describe peptide/ polypeptide hormones
- string of amino acids
- small monomers e.g. thyrotropin releasing hormone (TRH); 3 aa
- large multimeric proteins containing several subunits e.g. thyroid-stimulating hormone (TSH), luteinizing hormone (LH), and insulin (Ins)
- polypeptide hormones can have upwards of 200 residues
- larger protein hormones can be very complex in both primary and secondary structure and are often subject to post-translational modifications such as proteolytic processing and glycosylation, necessary to produce functional hormone
- water soluble; may or may not be associated with carrier/ binding proteins (to cross membrane)
Describe steroid hormones
- derived from cholesterol metabolism, 4 hydrocarbon rings with various side chains
- lipid soluble (requires serum binding proteins - transporter e.g. CBG-corticoidsteroid binding globulin) help to regulate steroid bioactivity - only free steroid is available to cell
- examples: testosterone, estrogen, vitamin D
Describe amino acid derivative hormones
- derived from the metabolism of phenylalanine and tyrosine to produce L-dopa, dopamine, norepinephrine and epinephrine, all of which function as neurotransmitters
- thyroid hormones triiodothyronine (T3) and thyroxine are produced from the biological iodination of tyrosine residues in thyroglobulin, which are then coupled and cleaved from the parent globulin
- examples: epinephrine, thyroxine (T4)
- need carrier protein
List some examples of hormones working within the human body
- the gut secretes its own series of hormones to regulate food intake and digestion (CCK, ghrelin, gastrin, secretin, NPY, etc.)
- the heart secretes ANP, an important factor in regulating vascular tone and volume
- the kidneys secrete EPO which increases erythrocyte formation
- the liver secretes angiotensiongen (angiotensin precursor), IGF-I and thrombopoietin (increases platelets)
- fat produces many “adipokines” e.g. leptin
- most cells produce locally-acting growth factors and cytokines
Describe the regulation of endocrine secretion
- several schemas for regulation from endocrine gland. most secretion controlled by:
1. negative feedback
also have:
2. positive “feed forward”
Describe negative feedback regulation of endocrine secretion
Can occur in a variety of states:
1. between 2 hormones e.g. TSH and T3 - tissue A produces hormone A, goes to act on tissue B, which produces hormone B, which goes back to tissue A to stop production of hormone A
2. between a hormone and a metabolite e.g. PTH and Ca++ - parathyroid tissue produces hormone PTH which acts on bone, and changes Ca++ levels, and calcium sensors in parathyroid gland shut down production of PTH
3. between antagonistic pairs of hormones e.g. insulin, glucose, glucagon - insulin (beta cells of pancreas) acts to lower blood glucose, while glucagon (alpha cells of pancreas) acts to increase blood glucose
Describe feed forward regulation
- one hormone positive feedback on another
- e.g. increased estrogen has positive feed forward effects on LH + FSH (increased production - release)
- in comparison progesterone has negative feedback on Lh + FSH
Describe the common characteristics shared by all hormones
- receptor specificity:
- only certain cells respond to a given hormone
- some cells are targets for more than one hormone
- a cell must have the appropriate receptor to respond to a hormone - a single hormone may elicit different responses in each target tissue
- single processes can be altered by multiple hormones (e.g. serum glucose homeostasis)
What are the factors affecting hormone action?
- hormone production/ release
- regulation of gene expression by other hormones and cytokines
- protein translation/ mRNA stability
- availability of necessary substrates, enzymes and energy (enzyme levels/activity)
- secretion
- innervation (unique to neuronal hormones)
- substrate/ energy availability
effect of hormone production
- more hormone present at a given target cell will lead to the activation of more receptors (at least until receptors are saturated)
- constant exposure to high levels of hormone may eventually lead to down-regulation of the receptor in the target cell(s) - not good thing
variable release rate into blood (so not too many hormones produced at once) -e.g. circadian rhythm
- fine tunes physiological responses
- prevents receptor down regulation
- attenuates negative feedback due to constant exposure
2. Serum carrier proteins e.g. SHBG, CBG, IGFBP3 (transport - important for steroid hormones)
- solubility
- stability
- metabolic clearance
- bioavailability
3. Converting / deactivating enzymes (in plasma and target cells) - may make hormones more or less potent, affect before reach target
- ACE-angiotensin converting enzyme
- ECE- endothelin converting enzyme
- COMT- catecholamine o-methyltransferase
4. Metabolic clearance (if these organs are functioning properly should restrict/decrease time hormone remains active)
- cellular uptake
- liver
- kidney
5. Receptors and signal transduction (
- specificty of hormone action is achieved through receptor expression and available signalling patjways
- signal amplification - 1 hormone-receptor complex activates many second messengers
- compartmentalization of “signalosomes” - creation of distinct cytoplasmic domains
Describe signal amplification
- each hormone/ receptor complex produces multiple second messenger molecules (e.g. cAMP, PKC, Ca++)
- each second messenger molecule activates different signalling cascades (protein phosphorylation)
- end result is generation of multiple copies of an mRNA, functional phosphorylated protein
What are the two broad categories of hormone receptors?
- cell surface (membrane) receptors - for water-soluble ligands and large ligands (e.g. peptides, polypeptides, aa derivatives, ions, cytokines)
- intracellular receptors - for lipid soluble ligands (e.g. steroid, thyroid hormones, vit D)
What are the 4 types of cell surface receptors?
- G-protein-coupled receptors (GPCR) e.g. receptors for LH, GnRH, angiotensin, Ca++
- Tyrosine kinase receptors (TKR) e.g. receptors for insulin, FGF, NGF
- Tyrosine kinase-associated receptors (TKAR) e.g. receptors for GH, PRL, leptin
- Receptor activated ion channels
Describe the lipid-soluble receptors (intracellular)
- e.g. steroids, thyroid hormone, vit D, retinoic acid
- pass through plasma membrane
- bind cytosolic steroid receptor (together become transcription factor)
- translocate into the nucleus, bind DNA promoters (DNA directly)
- cause changes to DNA transcription/ translation (increase / decrease) -> causes increase or decrease or protein production
- steroid synthesis all occurs through the derivation of cholesterol and are produced in adrenal gland/ cortex
- what matters is activity of enzymes (impacts which hormones are concentrated - what adrenal can make)
- steroid hormones: progesterone, aldosterone, cortisol, oestradiol, DHT, testosterone
Describe steroid secretion
- passive diffusion down the concentration gradient
- steroids circulate in plasma bound to carrier proteins
e.g. SHBG (sex hormone binding globulin), CBG (corticosteroid binding globulin)
Describe the mechanism of action of steroid hormones
+ inactivation
action
- HSP - heat shock protein, also can help regulate (increase/ decrease transcription/ translation) - regulate activation of cytosolic NR
- bind co-repressors (down-regulate transcription) or co-activators (up-regulate transcription)
inactivation
1. subtle changes in the ring structure of the molecule (oxidation, hydroxylation)
2. conjugation to organic acids (more polar), thereby increasing aqueous solubility -> excreted in urine (may test athletes for steroids in urine) - metabolic clearance
Describe neuroendocrinology
- the hypothalamus is the primary region of integration between the central nervous and endocrine systems
- input from array of neural, humoral, and endocrine sources are processed, coordinated and then relayed into action- secrete factors which stimulate or inhibit anterior pituitary function
- together the hypothalamus and pituitary are master regulators of human physiology