Hormone Cell Interaction

Question 1

Endocrine hormones

Answer 1

. Released by glands into circulation

. Affects distant target cells

Question 2

Neurohormones

Answer 2

. Secreted by neurons into circulation

. Influences distant target cells

Question 3

Paracrine

Answer 3

. Secreted by cells into ECF affecting neighboring cells of different type

Question 4

Cytokines

Answer 4

. Peptides secreted by cells into ECF that function as autocrines, paracrines or endocrine hormones

Question 5

Classes of hormones

Answer 5

. Peptides/proteins
. Steroids
. AA derivatives

Question 6

Peptides/proteins hormone class

Answer 6

. 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

Question 7

Steroid hormone class

Answer 7

. Lipid soluble
. Readily released as they are synthesized
. Not stored
. Require plasmatic protein transporters
. Interact w/ intracellular receptors to influence protein synthesis

Question 8

Amino acid derivative hormone class

Answer 8

. 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

Question 9

Competitive antagonist effect on potency and efficacy

Answer 9

. Antagonist dec. potency but does not change efficacy

. Degree of shift depends on affinity and receptor coupling of competing chemical

Question 10

Magnitude of biological responses mainly depends on ____

Answer 10

Number of hormone-receptor complexes
. Formation of complexes is non-covalent and follows 1st order molecular kinetics
. Affinity constant = [HR]/[H] x [R]

Question 11

Is the hormone considered in [H] free or bound to protein?

Answer 11

free

Question 12

Hormone secretion

Answer 12

. 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)

Question 13

Metabolic clearance

Answer 13

. 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

Question 14

Hormone half life

Answer 14

. 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

Question 15

Affinity in hormones

Answer 15

Receptors must have high affinity bc free hormone is in low concentrations

Affinity = [HR]/[H] x [R]

Question 16

Equilibrium dissociation

Answer 16

. 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

Question 17

Concentration of receptors

Answer 17

. 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

Question 18

Exception condition when Kd and ED50 are not equivalent

Answer 18

. When the max biological response of target cell occurs despite all receptor sites NOT bring occupies
. Kd is then lower than the ED50

Question 19

T/F endocrine feedback loops are proportional

Answer 19

T

. Rate of secretion varies btw 0 and maximal rather than on or off

Question 20

Essential component of feedback loop

Answer 20

. 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

Question 21

Positive feedback loop

Answer 21

. 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

Question 22

Permissiveness

Answer 22

. Hormone A must be present for full expression of hormone B’s effect

Question 23

Counter regulatory hormones

Answer 23

. Different hormones have opposing effects on the same variable

Question 24

Trophic

Answer 24

. Hormones stimulate the secretion of another hormone and usually the growth of that endocrine gland

Question 25

Syngery

Answer 25

. 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

Question 26

Protein hormones are secreted by ____

Answer 26

Ca-dependent exocytosis | . Secretory vesicles fuse w/ plasma membrane, vesicle opens releasing contents into extracellular space

Question 27

Peptide hormone transport

Answer 27

. Hydrophilic and soluble in plasma | . Do not require transport proteins except somatomedins (IGF)

Question 28

Peptide metabolism

Answer 28

. 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)

Question 29

Classes of steroids

Answer 29

. Estrogens . Androgens (testosterone) . Glucocorticoids (cortisol) . Mineralcorticoids (aldosterone)

Question 30

Steroids are produced in what locations?

Answer 30

. Adrenal cortex . Testes . Ovary . Placenta

Question 31

Steroid synthesis

Answer 31

. 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)

Question 32

Rate limiting step in all steroid synthesis

Answer 32

. Conversion of cholesterol to pregnenolone in mitochondria

Question 33

Rate of steroid secretion is controlled by the rate of ____

Answer 33

Steroid synthesis

Question 34

Transport of steroids in plasma

Answer 34

. 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

Question 35

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

Answer 35

T

Question 36

Steroid mechanism of action

Answer 36

. 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

Question 37

Steroid metabolism

Answer 37

. 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

Question 38

Enzymes that control formation of eicosanoids

Answer 38

. Thromboxane . Prostacyclines . Prostaglandins . Leukotrienes

Question 39

Prostaglandins

Answer 39

. 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)

Question 40

Leukotrienes

Answer 40

. 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

Question 41

Thromboxanes

Answer 41

. Role in hemostasis . thromboxane A2 is most important . Platelets convert PGH2 into TA2 which aggregates platelets, induce platelet aggregation, and induce vasoconstriction

Question 42

Prostacyclins

Answer 42

. Endothelial cells can convert PGH2 to prostacyclin I2 (PGI2) which inhibits platelet aggregation and dilates blood vessels