Hormone Cell Interaction Flashcards
Endocrine hormones
. Released by glands into circulation
. Affects distant target cells
Neurohormones
. Secreted by neurons into circulation
. Influences distant target cells
Paracrine
. Secreted by cells into ECF affecting neighboring cells of different type
Cytokines
. Peptides secreted by cells into ECF that function as autocrines, paracrines or endocrine hormones
Classes of hormones
. Peptides/proteins
. Steroids
. AA derivatives
Peptides/proteins hormone class
. Synthesized as prohormone or pre-pro-hormone
. Stored in membrane bound secretory vesicles in cytoplasm
. Released by Ca-dependent exocytosis
. Circulate in blood as unbound form: have short half-life times
. Do not cross cell membranes
. Interact w/ membrane receptors
. Second messengers required for signal transduction
Steroid hormone class
. Lipid soluble
. Readily released as they are synthesized
. Not stored
. Require plasmatic protein transporters
. Interact w/ intracellular receptors to influence protein synthesis
Amino acid derivative hormone class
. Thyroid hormones: stored in follicle as part of thyroglobulin, cross cell membranes, transported in blood bound to proteins, have intracellular receptors
. Catecholamines: stored in membrane-bound vesicles, don’t cross membranes, transported in blood free or loosely assoc. w/ proteins
Competitive antagonist effect on potency and efficacy
. Antagonist dec. potency but does not change efficacy
. Degree of shift depends on affinity and receptor coupling of competing chemical
Magnitude of biological responses mainly depends on ____
Number of hormone-receptor complexes
. Formation of complexes is non-covalent and follows 1st order molecular kinetics
. Affinity constant = [HR]/[H] x [R]
Is the hormone considered in [H] free or bound to protein?
free
Hormone secretion
. Most hormones released in short pulsatile bursts
. To inc. secretion the bursts happen more frequently
. Frequency of bursts and oscillations of frequency depends on external factors (light-dark, sleep-wake)
Metabolic clearance
. Catabolic clearance rate (MCR) of hormone represents the volume of plasma cleared of hormone per unit time
. Occurs primarily via removal and metabolism in liver and kidneys
. Some hormones removed or metabolized after uptake by target cell
. Half-life of hormone is inversely related
Hormone half life
. Ranges from 2-3 minutes to 6/5 days
. Polypeptide and protein hormones that freely dissolve in plasma H2O generally have a shorter half-life than steroid hormones that are largely bound to transport proteins
Affinity in hormones
Receptors must have high affinity bc free hormone is in low concentrations
Affinity = [HR]/[H] x [R]
Equilibrium dissociation
. Concentration of hormone at specified equilibrium conditions that is required for binding to 50% of the receptor sites
. Lower the Kd concentration, the higher the affinity
Concentration of receptors
. Receptor concentration can be unregulated or downregulated
. They are continuously synthesized and degraded
. Modulation by primary hormone is homologous regulation (low conc. Of primary hormone inc. receptor conc.)
. Modulation by non-primary hormone is heterologous (different hormone inc. another hormone’s receptors in target cell)
. Biological response of target cell is directly proportional to number of occupied receptor sites
Exception condition when Kd and ED50 are not equivalent
. When the max biological response of target cell occurs despite all receptor sites NOT bring occupies
. Kd is then lower than the ED50
T/F endocrine feedback loops are proportional
T
. Rate of secretion varies btw 0 and maximal rather than on or off
Essential component of feedback loop
. Stimulus
. Sensor
. Setpoint: required conc. Of hormone
. Integrating center: comparison of actual and required conc. Of controlled variable occurs (and where error signal develops)
. Effector: mechanism that returns level of controlled variable toward desired setpoint
Positive feedback loop
. Non-regulatory and unstable
. Deviation from setpoint will be inc. by effector
. Example: parturition: oxytocin stimulates and enhances labor contractions, as baby moves down pressure receptors w/in cervix send signals to produce more oxytocin
. When stimulus to receptor ends, the hormone production stops
Permissiveness
. Hormone A must be present for full expression of hormone B’s effect
Counter regulatory hormones
. Different hormones have opposing effects on the same variable
Trophic
. Hormones stimulate the secretion of another hormone and usually the growth of that endocrine gland
Syngery
. Occurs when 2 hormones produce the Sam biological response
. Simultaneously produce a response that is greater than the sum of the individual responses to each hormone
Protein hormones are secreted by ____
Ca-dependent exocytosis
. Secretory vesicles fuse w/ plasma membrane, vesicle opens releasing contents into extracellular space
Peptide hormone transport
. Hydrophilic and soluble in plasma
. Do not require transport proteins except somatomedins (IGF)
Peptide metabolism
. Remain in bloodstream only for a short time after secretion
. Receptor-mediated degradation is 1 pathway for metabolism of some peptide hormones
. For most peptide/protein hormones, kidney and liver are major sites of hormonal degradation
. Polypeptides and lower molecular weight protein hormones are more readily filtered by kidney and excreted
. Polypeptide hormones have a shorter half-life (min) than larger protein hormones (hours)
Classes of steroids
. Estrogens
. Androgens (testosterone)
. Glucocorticoids (cortisol)
. Mineralcorticoids (aldosterone)
Steroids are produced in what locations?
. Adrenal cortex
. Testes
. Ovary
. Placenta
Steroid synthesis
. LDL Major source of cholesterol
. Binding of LDL to membrane receptor causes internalization of LDL-receptor complex via endocytosis
. Cholesterol is then stored in esterified form
. Upon ACTH or LTH stimulation, free cholesterol is released from lipid droplet by cholesterol esterase (activated by PKA)
. Free cholesterol transported to mitochondria by steroidogenic acute regulatory (StAR) protein and internalized by peripheral-type benzo receptor (PBR)
. Cholesterol modified by cytochrome P450s and other enzymes to produce pregnolone (common steroid precursor)
Rate limiting step in all steroid synthesis
. Conversion of cholesterol to pregnenolone in mitochondria
Rate of steroid secretion is controlled by the rate of ____
Steroid synthesis
Transport of steroids in plasma
. Lipophilic (little dissolved in plasma, most bound to transport proteins)
. Hormone bound to protein in equilibrium w/ free hormone in plasma
. Dissociation of hormone from carrier protein is slow process and hormone remains attached to specific carrier as blood transverse capillary beds
. Dissociation of hormone from non-specific protein carriers does occur in capillary beds
. Binding and unwinding keeps free hormone conc. Constant
T/F in presence of intact regulatory systems, alterations in hormone-binding proteins do not chronically alter endocrine status bc the free conc. Of hormone is adjusted back to setpoint
T
Steroid mechanism of action
. Receptor in cell nucleus (can be in cytoplasm)
. Binding of hormone to receptor activated DNA-binding domain
. Hormone receptor complex binds to specific sequences of DNA to modify transcription
. Biological effect takes longer compared to response via second messenger production
Steroid metabolism
. Have long half-life
. Metabolized in series of reduction reactions that primarily take place in liver
. Metabolites conjugated w/ sulfates or glucouronides and secreted into bile or plasma. For excretion via GI or kidneys
Enzymes that control formation of eicosanoids
. Thromboxane
. Prostacyclines
. Prostaglandins
. Leukotrienes
Prostaglandins
. Generated from COX enzyme
. Modulate many biological activities
. Type synthesized in a particular tissue is determined by specific complement of enzymes w/in cell
. Interact w/ receptors on local target cells in paracrine or autocrine fashion
. Very short half-life (minutes)
Leukotrienes
. Generated from arachidonic acid via 5-lipoxygenase
. Classified as LTB4, LTC4, LTD4, LTE4, and LTF4
. Interact w/ receptors on local target cells in paracrine or autocrine way
. LTB4 is important in inflammatory response
. LTC4, D4, and E4 are potent constrictors of smooth mm. In trachea, lung, and arterioles
. Stimulate mucous secretion
. Play role in asthma, gout, IBD, RA, psoriasis, adult respiratory distresss yndrome, and allergies
Thromboxanes
. Role in hemostasis
. thromboxane A2 is most important
. Platelets convert PGH2 into TA2 which aggregates platelets, induce platelet aggregation, and induce vasoconstriction
Prostacyclins
. Endothelial cells can convert PGH2 to prostacyclin I2 (PGI2) which inhibits platelet aggregation and dilates blood vessels
