Intro to Endocrine Physiology Flashcards
What is Endocrinology
Ways in which cells communicate
- autocrine
- paracrine
- endocrine
- neurocrine
- neuroendocrine
Endocrinology: the study of the devlivery of regulatory information from one cell to a target cell through a chemical messenger - ususally a hormone– and often to a cell which is distant from the originating cell
(this varies from the nervous system in that the nervous system uses electrical impulses to stimulate release of other NT, but the endocrine releases hormones which directly trigger a secondary effect)
Autocrine = hormone or other chemical messenger which is released then the directly acts back on the original cell-itself
Paracrine = the chemical messenger is released but acts locally, such as on the cells next to or near by
Endocrine = chemical messengers (hormones) are released from the endocrine cell and travel through the blood stream to their target cell elsewhere within the body (distant)
Neurocrine = a chemical synapse of communication between two neruonal cells
Neuroendocrine = the neuron cells release their contents into the general circulation, which travel to a specific target cell and act (ex. ADH from pituitary in brain is released and travels through blood to the kidney)
What is a Hormone
Chactacteristics of endocrine hormones
Hormone = a biochemical messenger which is produced from a ductless gland (not released from a duct, but instead transported through circulation)
- each hormone has an identifiable target cell with receptors for which the hormone can bind to
- the function of hormones is to regulate development, growth and metabolism
- their action at the target cell will effect downstream signalling within the cell and additional pathways
Characteristics of Hormones
- exisit in VERY small concentrations (pico or nanograms)
- released in response to a VERY SPECIFIC stimuli
- distrubuted through circulation
- can exisit as free within plasma or bound to proteins (if free, able to work directly on the target receptor, however also able to be readily regradeed; thus bound to a protein helps to make the likelihood of being degraded less)
- have specific target receptors within specific organs; which elicit a response when they bind (regulatory or metabolic in nature)
What are some Endocrine Organs
what are non-traditional endocrine organs?
- pituitary gland
- thyroid gland
- parathyroid gland
- adrenal gland
- endocrine pancreas
- reproductive tissue
- heart! (ANP)
- placenta (GH)
- small intestine (GLP-1 & GIP)
- stomach
- kidney (EPO, vit D activiation)
- CNS
Types of Signaling Molecules/Hormones
3
how are thye different (structure)
Peptide Hormone
- these are smaller chains of polypeptides
- WATER SOLUABLE: therfore unable to enter inside the cell and bind, so their receptors on teh target cells are located on the membrane, cell surface
- water soluable, dissolved easily in the serum without the need for a carrier protein to bind to them BUT that makes them easily degraded
- secrete quickly, travel quickly but degraded quickly too
- example: ACTH
Steroid Hormone
- all deriviatives from cholesterol; thus lipid soluable
- if lipid soluable, means they can pass through the cell membrane with ease, therefore thier target receptors are usually INSIDE the cell
- spcifically, these steroid hormones bind to receptors inside the cell and act direclty on the DNA
- example: estradiol
Tyrosine Derivative
- examples include thyroxine, Epinephrine, norepinephrine
- a combo, thyroxine acts like a steroid hormone
- epi and NE act like peptide hormones
How are hormones synthesized
how are their production regulated
what is the physiology
3 types of how the hormone is made in relation to its sequence
stimulated production in the response & regulation by
- other hormones
- neurotransmitters
- sympathetic or parasymatheic innervation of the gland itself
- environmental signals (like sleep)
Physiology
- a signal peptide triggers the beginning of the protein synthesis
- signal recognition partilce binds and assists with the creationg of the new peptide chain
- it docks and enters the endoplasmic reticulum when the sequence is made
- stored in the ER until its needed, then released
3 ways the hormone is synthesized
Preprohormone
- the hormone is syntehsized alone, on its own seequence as a pre-prohormone: needs to be convered to its hormone
Prohormone: Multiple copies
- multiple copies of the hormone within one sequence
Single Precursor: multiple different hormones arise from a singal sequence (ex. in addisons disease; they are tan and have too much ACTH)
all of these processes about when to splice, convert etc. is regulated by feedback loops
How is hormone secretion regulated
where are the different classes of hormones stored in a cell
what are the forms in which the hormones can be released into the circulation
- the body detects a change in its normal homeostasis
- this triggers a response (chemical or mechanial)
- these responses signal an activation in the secretion of the proper hormone to be released from its storage in the ER , trasnported to the golgi for processing and packaging (coverting the prohormone to the hormone) then vesicles transport the hormones just made into circulation
Peptide Hormones
- (NE/Epi because they act like these) & ACTH
- stored in secretory vesicles to be released
Thyroglobin
- precursors stored as colloid (within the substance?)
Steroids
- lipid solubale; thus no need to be stored within the cell
- so they’re made slowly and immediately released as they’re made
Release of Hormones : any of these mechanisms
- when they become biologically active they’re released
- some are released once bound to the carrier
- some are carried to the target then become biologically active when they get there
remember only free hormones NOT bound to a carrier proteins have the ability to be biologically active, but the free hormones can be regularly degraded within the circulation if not bound to a carrier
How is the release of hormones regulated?
Negative-Feedback Regulation
- majority of hormone regulation is negative feedback
- something triggers the need for a hormone to be released
- organ releases hormone -> acts on the target cell
- target cell releases additional hormone or triggers release of additional hormone which travels BACK to original hormone
- turns off the signal of the originial release
Positive-Feedback Regulation
- most common in female reproductive system during menstration
- hormone released, acts on target
- triggers additional hormone release which goes back and binds to orignial organ
- triggers more release of the first hormone
hormone secretion is often pulsitile; in that there are specific times of the day when the hormone my be more plentiful than other times
example: cortisol peaks right in early morning; LH peaks at various hours throughout the day
Cellular Target Reponse: what happens
Receptor Specifics: where are they located
disucss receptor saturation
Target Cell Response
- receptor binding to the hormone
- triggers activation and a reponse cascade
Receptors
- have a specific location on target cell (depending on the hormone which binds to it and its makeup)
- receptors have their own characteristics; functioning as a message transduction point to intake the signal and ellict a response
Receptor Locations
- cell membrane: Cell surface receptors = water soluable hormones (because they cant pass into cell)
- cytoplasm or nucleus = lipid soluable hormones (since they can pass in)
Receptor Saturation
- there is a maximum of ligand bound to receptors — more of an asymptote curve in that initially; best response is when only a FEW receptors are bound
- after the initial; each consecuative binding results in a smaller increased response
- thus, the greatest response is when the receptors are undersaturated aka smallest amount of hormone triggers greatest response
Cell Surface Receptors
- number of receptors
- strucutre of receptors
- Types
- approx. 10-20,000 receptors on the cell surface; thus the cellular response is NOT limited by the number of receptors avalible
Structure
- have receptor binding domains
- contain G proteins or other singaling cataylic proteins
- phosphorylation/dephos. of the signal going into teh cell
- intracellular cascades (of secondary messengers) DAG, IP3, Ca2+ (calcium is a big player; moves out of ER into cytoplasm)
Names/Types
- G-protein couple receptor (beta-adrenergic recptors, vasopressin, AGII, DA, LH, etc.) = 7 transmembrane domains which trigger secondary messengers (mainly calcium)
- insulin receptors
- EGF receptors
- ANP receptors
insulin and EGF receptors have kinase phosphorylation to trigger intracelluar responses
Intracellular Receptors
- structures
- how they work
- intracellular receptors exisit on the cytoplasm or on the nuclear systems
- these hormones must be lipi soluable to pass through the membrane and diffuse into the cytosol or into nucleus
- steroids can be bound to a plasma binding protein, and diffuse as a complex through the cell
How they Work
- steroids (like thyroid hormones) bind to carrier proteins through the circulation
- there is a relative equilibrium between amt. free and amt. bound
- only the FREE hormone with traverse the plasma membrrane
- so it detaches from its plasma binding protein, travels into cell freely, binds to receptor in the cell and then a shape change occurs to go impact the DNA/RNA of the cell
Receptor Strucutre once inside the cell
- once inside; shape change occurs but two areas remain the same
- 1. ligand-binding domain
- 2. DNA-binding domain (zinc fingers) which directly grab the DNA
- the N terminus is what can change dramatically about this intracellular receptors
evidence shows that there can be binding of the hormone without binding to the DNA; emphaszing that these are two seperate locations on the receptor
Explain the process of upregulation and downregualtion of receptors
Up-Regulation: occurs when there is LITTLE ligand (hormone) avalibe, so the cell responds by INCREASING the number of receptors (to increase its chances of binding to one of the rare hormone molecules!)
Down-Regulation: occurs when there is TOO MUCH ligand (hormone), so the cell responds by DECREASING the number of receptors (its so over stimulated it needs to be more picky about how much is binding)
down regulation is what is seen in the patho od t2DM and insulin resistance due to too much glucose in the blood stream
Once bound, the hormones response can be altered by post-receptor influences, additive, antagonist or synergistic in nature
How are Hormones Degraded
Inactivation of the hormone occurs in the…
- blood
- ECF
- liver
- kidney
- at teh target cell
the liver is the main site of degradation, then the kidney –> thus kidney and liver diseases impact the bodies ability to breakdown hormones
Hormone Action within the Target Cell
- when is it triggered?
Compare and contrast the peptide/NE/epi v steroid/thyroid hormones in the following ways
- how they exisit in circulation
- amt in plasma
- receptor location
- mechanism
- onset of action
cells normally have some sort of basal function, in that can be altered by a hormone
- a cellular response is not seen until the hormone concentration reaches a threshold
Comparisons
Within circulation
- water soluable are free
- lipid are bound to carriers
concentration in serum
- water soluable flucuate
- lipid soluable have slow changes
receptor location
- water solauble = on surface
- lipid = within the cell
Mechansim
- water = activate enzymes
- lipid: directly impact DNA
onset of action
- water = rapid
- lipid = slow (hours)
Where do defects in the Hormone/Receptor pathwat occur (4)
what are some hormone disorders
how does the immune system play a role
Defects
- synthesis/secretion issues
- circulation issues
- receptor issues
- post-receptor issues (with second messengers)
hormone disorders
- too much, not enough
- impaired cellular response (at the receptor to bind, activation of the proper pathway, intracellular pathway issue)
- biologicall inactive variants of hormones
Immune system Role
- lots of cross over between the two
- specific mechanisms inhibit recognition of the self-antigens of immune system is due to peptide hormone receptors
- but dysfunction in this ability can lead to endocrine autoimmune disorders
