Hormone-Cell Interaction Flashcards
Endocrine definition
chemical messenger produced by 1 cell type that acts on distant cells
Autocrine definition
chemical messenger produced by 1 cell type that acts on the same cell
Paracrine definition
chemical messenger produced by 1 cell type that acts on a neighboring cell
Hormone
produced in 1 tissue, released in blood, and carried to target; or more simply a chemical with autocrine, paracrine, or endocrine function
Endocrine Hormone
released by glands into the circulation, affecting distant target cells
Neurohormones
secreted by neurons into the circulation, influencing distant target cells
Paracrines
secreted by cells into the ECF affecting neighboring cells of different type
Autocrines
secreted by cells into the ECF affecting its own function
Cytokines
peptides secreted by cells into the ECF that can have autocrine, paracrine, or endocrine function
3 main classes of hormones
peptide, steroid, amino acid derivative
Peptide hormone (hydrophilic or polar)
synthesized as pre-hormone, stored in vesicle, released by Ca-dependent exocytosis, circulate unbound in blood, short half-life, interact with cell membrane, require 2nd messenger system
Steroids (hydrophobic or nonpolar)
released upon synthesis, require plasmatic protein transporters, interact with intracellular receptors in target cells –> protein synthesis
Amino Acid Derivatives (tyrosine)
Thyroid Hormones and Catecholamines
Thyroid Hormones
stored extracellularly in follicle of thyroid as part of thyroglobulin, crosses cell membrane, blood transport bound to protein, have intracellular receptors
Catecholamines
stored in vesicles, do not cross membrane readily, transported in blood free or loosely associated w/ proteins
What 2 glands secrete hormones almost entirely due to neural stimuli
adrenal medulla and pituitary
Nervous system and endocrine system work together to maintain homeostasis, this is done by
nervous system short term and endocrine for long term
Hormone receptors
required by cell for response, can be on membrane, in cytoplasm, or in nucleus
Receptor-Hormone Interaction - Threshold
minimum concentration of hormone to elicit a response
Receptor-Hormone Interaction - Saturation
response plateaus when all receptors are occupied, regardless of excess increase in hormone concentration
Receptor-Hormone Interaction - Sensitivity
Concentration of hormone required to elicit 50% of maximal response
Receptor-Hormone Interaction - Competition
Substance that may also bind receptor (endogenous and exogenous)
Receptor-Hormone Interaction - Agonists
Chemical agent that binds receptor and elicits the same response
Receptor-Hormone Interaction - Antagonist
Chemical agent that occupies the receptor but does not elicit a response
Receptor-Hormone Interaction - Responsiveness
determined by the maximal response and dependent on number of receptors
A reduction in the number of receptors will result in a reduction in
maximum responsiveness
Sensitivity reflects the receptors
affinity for the hormone and the receptors availability
A competitive inhibitor would have what effect on sensitivity and responsiveness?
It would require a higher concentration of hormone to produce the same result (decreasing the sensitivity), but the maximal response does not change
An antagonist __________ potency/sensitivity and _______ efficacy
reduces; does not effect
The magnitude of the response is dependent on ________________
the hormone-receptor complex
the hormone-receptor complex is non covalent and follows
1st order kinetics
Kinetics affinity constant of the receptor for the hormone
(K) =
[HR] / ([H] x [R]) (% receptors bound)
The hormone concentration in blood [H]
refers to the concentration of FREE hormone (unbound to transport proteins)
Plasmatic protein is determined by
secretion, metabolism, and binding to plasma proteins
Most hormones are released
in short bursts or in oscillations (circadian)
Metabolic Clearance Rate (MCR)
volume of blood cleared of hormone per unit of time
A high MCR means
the hormone in quickly cleared from the blood and that hormone has a SHORT HALF-LIFE
Metabolic clearance is performed by
Liver, kidney, or metabolized after uptake by target cell
Half life of a hormone is __________ proportional to the MCR
inversely
Half-life for a catecholamine is
2-3 min generally
Half-life for a thyroid hormone is
6.5 days generally
Which has a shorter half-life and why, steroid or peptide hormone?
peptide, it is unbound
Affinity
liklihood that the receptor will bind the hormone with a given [H]
Affinity can be determined by
ka (association constant) / kd (dissociation constant) = [HR] / [H] x [R] = K
equilibrium dissociation constant
the concentration of hormone (at equilibrium) that is required for binding to 50% of the receptor sites
The lower the dissociation constant Kd
the HIGHER the affinity (a smaller amount of H is required to elicit a response)
Concentration of receptors:
receptors are constantly synthesized and degraded; regulation of this allows the cell to alter its physiological response to a hormone
Up regulation
means to synthesize more receptors or slow the degradation; in response to LOW [H] levels
Down regulation
means to synthesize less receptors or speed degradation; in response to HIGH [H] levels
Homologous regulation
modulation of number of receptors by the hormone itself (NE can increase NE receptors at low [NE])
Heterologous regulation
modulation of number of receptors by non-primary hormones (Estrogen can increase Progesterone receptors)
The Kd concentration is normally equivalent to
the number of receptors occupied.
ED50
concentration of hormone required to elicit 50% of maximal response
Kd is normally equivalent to
ED50
If Kd does not equal ED50 then
this means that the 100% response occurs even when 100% of receptors are NOT occupied
Spare receptors
at maximal response, there are some spare receptors; allows for rapid response and termination of response, or obtaining a response with a low [H] with relatively low affinity
5 components of a feedback loop
Stimulus, sensor, setpoint, integrating center, and effector
The stimulus of a feedback loop
the hormone, or variable related to the hormones action (ions) - controlled variable
Setpoint of the feedback loop
the required concentration of the stimulus
Integrating Center of the feedback loop
where comparison occurs between the setpoint and the actual concentration and an “error” message develops
Effector of the feedback loop
mechanism that returns the level of stimulus back to the setpoint
Effector causes opposite action
if stimulus concentration is LESS than set point, effector causes an increase to stabilize the stimulus
All hormones use ___________ feedback mechanisms
Negative
Positive feedback
a deviation from setpoint causes effector to increase the deviation (non-regulatory and Unstable)
Positive feedback occurs by
further increasing the [H] or increasing the # of receptors
Example of positive feedback
Labor and oxytocin levels; as the baby presses down on pressure receptors in the cervix oxytocin levels rise and cause more forceful contractions until the pressure is relieved
Permissiveness
The presence of a hormone is required for another hormone to have its FULL EFFECT
Example of permissiveness
presence of thyroid hormone is permissive for the effect of epinephrine on lipolysis (thyroid hormone has a small effect on lipolysis alone)
Counter regulatory hormones
hormones that have opposing effects on the same variable
Example of counter regulatory hormones
Glucagon is counter regulatory to insulin
Trophic hormones
hormone that stimulate the secretion of another hormone and/or the growth of that endocrine gland
Synergy
when 2 hormones that have the same biological response, produce a greater response together than the individual responses alone
Example of Synergy
Thyroid and Growth Hormones have synergistic effects on bone growth
Peptide hormone synthesis, storage, and secretion
synthesized as a pre-pro-hormone, stored in a secretory vesicle, released via Ca-dependent exocytosis into ECS for RAPID response
Peptide hormone transport
Hydrophilic and soluble in plasma (except somatomedins and IGF require transport proteins)
Post-receptor events
Bind integral receptors on plasma membrane of effector cell causing 2nd messenger cascades
Hormone receptor/Ion channel
Hormone binding opens ion channels that can alter membrane potential or act as a 2nd messenger itself (Ca)
Hormone receptor/protein kinase
Hormone Binding causes phosphorylation (tyrosine phosphorylation if tyrosine kinase) which generates a biological response
Hormone receptor/ JAK
hormone binding activates JAK which phosphorylates specific proteins for a biological response
Hormone receptor/Gproteins
Hormone binding activates a G protein and causes an increase in the 2nd messenger which activates a protein kinase for phosphorylation of specific proteins
5 Major 2nd messengers
cAMP, cGMP, inositol triphosphate, DAG, Ca, Ca-calmodulin
cAMP/G protein (Gs)
Hormone binding –> GDP replaced with GTP on G protein –> activation of adenylyl cyclase –> converts Mg-ATP to cAMP (which ends when GTP is hydrolyzed) –> cAMP activates protein kinase
How does cholera toxin effect cAMP?
inhibits the conversion of GTP to GDP in which adenylyl cyclase would be constitutively on
cAMP/G protein (Gi)
GTP binding to G protein causes adenylyl cyclase inhibition (rather than activation)
Pertussis toxin effects cAMP pathway by
interfering with Gi, preventing the inhibition of adenylyl cyclase (constitutively active)
cAMP activates protein kinase by
binding to the regulatory unit of the kinase and causing a dissociation of the regulatory subunit and the catalytic unit; causing the kinase to be activated
Phosphodiesterase
metabolizes cAMP to inactive 5’-AMP
What if the same hormone binds the same receptor in a different cell?
the cell response may be different
What is a different hormone binds the receptor in the same cell?
It may produce the same effect by increasing cAMP
What accounts for different tissues differential response to cAMP increase?
cAMP may activate a different type of protein kinase OR the proteins subject to phosphorylation may be different depending on the proteins genetically expressed in that particular cell type
Protein hormone metabolism
circulate free and are free to excrete and metabolize
Major sites for protein hormone degradation
liver and kidney
The half life of polypeptide hormone is ________ than larger protein hormones
shorter
Steroid hormones are
lipophilic, have cholesterol as a common precursor
Steroids hormones differ by
functional group, degree of saturation, and length of side chain
4 classes of steroids include
estrogen, androgen, glucocorticoids, and mineralcorticoids
Steroids are produced mainly in the
adrenal cortex, testis, ovary, and placenta
Cholesterol for steroid hormone synthesis comes from
LDL in the liver, the lipid droplet is taken up by endocytosis and store din a non-membrane bound lipid droplet
cholesterol esterase
stimulated by trophic hormones –> PKA; causes free cholesterol release from the lipid droplet
Steroidogenic acute regulatory protein (StAR)
transports free cholesterol to the mitochondria
Peripheral-type benzodiazepine receptor (PBR)
receptor that allows internalization of free cholesterol by the mitochondria
Cytochrome P450
modifies cholesterol to pregnenolone
Pregnenolone
common precursor to all steroid hormones
Major steroid hormones:
aldosterone, cortisol, estradiol, and testosterone
The rate-limiting step of steroid hormone synthesis
cholesterol to pregnenolone by P450 in the mitochondria
pregnenolone in the testis
converts it to testosterone
pregnenolone in the adrenal cortex
converts it to aldosterone or cortisol
Storage of steroid hormones
lipophilic and therefore diffuse out of the cell into the ECS, no storage or pre-formed molecules required
Transport of steroid hormones
some hormone is dissolved in the blood, while most are attached to transport proteins (>50kDa). when free [H] decreases Hormone will release from the transport protein to raise the free concentration
Steroid hormone and its specific transport protein
high affinity, dissociation is slow, tightly bound to traverse capillaries, large transport protein to avoid glomerular filtration
If a hormone is loosely bound to a non-specific transport protein
when the complex traverses the capillary bed, the hormone will dissociate and diffuse into tissues
Hormones bound to albumin and pre albumin cause ____________ of the free hormone available to the tissues
underestimate
Example of non-specific transport protein
albumin and pre-albumin
An increase in transport proteins will increase the amount of bound hormone
decreasing the amount of “free” hormone in plasma
Control systems use which concentration for regulating plasma [H]?
FREE plasma concentration (if more is bound, then the body will secrete more into plasma until the FREE [H] rises to normal)
Mechanism of steroid hormones
receptor located in the nucleus or cytoplasm, binding to receptor causes activation of the DNA-binding domain which binds to DNA and turns on protein synthesis
Why does steroid hormone leave its transport protein and enter cells?
It has a greater affinity for the receptor
Steroid hormones are ___________ than peptide hormones
slower acting; they need to turn on gene transcription
Half life of steroid hormones
is longer than peptides because they are bound to transport proteins
Steroid metabolism
occurs mainly in the liver
Steroid halflives increase as their
affinity for transport proteins increases
Amino acid hormones: 2 major types
catecholamines (NE and Epi) and thyroid hormones
Amino acid hormones are derived from
tyrosine
Catecholamines act like
peptide hormones (soluble and bind plasma membrane receptors)
Thyroid hormones act like
steroid hormones (transport proteins –>intracellular receptors)
Phospholipase A2
main enzyme responsible for releasing arachidonic acid
Eicosanoids are formed from
arachidonic acid
Arachidonic acid
phospholipid component of the plasma membrane released by phospholipid A2 and C-beta
Cortisol inhibit
phospholipase A2
arachidonic acid can be converted to
thromboxanes, prostacyclines, prostaglandins, or leukotrienes
eicosanoids act as
2nd messengers (intracellular enzymes and ion channels or paracrine effects)
Prostaglandins
COX enzyme; useful for hemostasis, water excretion, gastric secretion, integrity of stomach lining, vascular reactivity (paracrine or autocrine function)
Leukotrienes
LOX enzyme; LTB-F4, LTB4 acts during inflammation and LTC-E4 are slow-reacting anaphylaxis
Thromboxanes
Platelets convert PHG2 to thromboxane A2 which induces platelet aggregation and vasoconstriction
Prostcyclines
endothelial cells convert PGH2 to PGI2 which inhibits platelet aggregation and causes vasodilation
NSAIDS reverse which eicosanoids
reverses COX and the productions of prostaglandins, prostacyclines, and thromboxanes
