Endocrine 1

Front 1

1. Hormones

2. Endocrine Glands
-specificity

3. Neurocrine factors

Back 1

1. endocrine effectors

2. organs whos func is to secrete hormones--> circulate throughout body --> specificity from receptors

3. Effectors released by nerves not glands into blood

Front 2

1. Amino acid derivatives

2. Peptides and proteins

3. Steroids

Back 2

1. From tyrosine: catecholamines and thyroid hormone

2. chains of AA from 3 to >100

3. Cholesterol derivatives

Front 3

Nervous:

Neurotransmitters

Specificity

Back 3

- travel via nerves

- effector is neurotransmiters

- specificity does not req a wide variety of discrete signalling substances

- transmitted more rapidly than endocrine bc does not travel though circulation

Front 4

Paracrine

Cytokines

Specificity

Back 4

- act over short distances via diffusion
- specificity: limited volume
- cytokines are effectors

Front 5

Autocrine

Cytokines

Back 5

- - act on the cell that produced it
- allows cell to respond to change in cells environment
- similar cells are close --? autocrine effectors cna be paracrine effectors
- leads to higher [] of efffectors

Front 6

Adhesion

Back 6

- effectors on the surface of cell that interact with receptors on the surface of another cell or the matrix supporting cells
--> responses in one or both cells

Front 7

Response of an organ or tissue to signal

Back 7

- sum of the response of its individual cells
- tissues have heterogeneous cell pop that respond diff to same signal
- local environments can cause cells to respond differently

Front 8

Receptors

Back 8

- bind signaling effectors
- have high specificity, need a certain shape
- exterior or interior
- cytoplasmic/nuclear receptors --> reg gene transcription

Front 9

1. Ligands

2. Second messangers

Back 9

1. bind to receptors

2. furhter regulate internal processes

Front 10

Receptors and response

Back 10

1. just binding --> response
2. dimerization to produce an effect
- may be caused by change in receptor structure or ligands that bind to mult receptors
3. G protein- 7 transmembrane regions

Front 11

Regulation of cell functions

Back 11

- ligand changes in structure (iwthout making or breaking covalent bonds)
-change in receptor structure --> trigger change in cell metabolism

Front 12

Types of changes

Back 12

1. Allosteric regulation
2. Reversible or irreversible covalent modification (REV: phosphorylation/dephosphorylation IRREV: protelysis or hydrolysis)
3. Physical location
4. Change #

Front 13

Dose response curve

Back 13

- describes effects of effecotrs on cells
- X axis: concentration or dose of effector (log scale)
- Y axis: cannot be 0 in absens e of effector, may be endogenous effecotr in the system or other effectors have same effect

Front 14

1. Eo

2. Emax

3. EC50

Back 14

1. value of the parameter in absence of added hormone

2. Emax- freq the concentration of an effector varies with time and it is more accurate to refer to the dose of effector rather than its concentration

3. concentration or dose of an effector that causes 50% of Emax

Front 15

1. Responsiveness

2. Sensitivity

Back 15

1. dec in responsiveness dec in EMax no change in EC50

2. dec in sensitivity --> shift in dose response curve to the R or inc in EC50 with no change in EMAX

Front 16

Kinetic anaylsis of ligand binding and action: efficacy and spare receptors

Back 16

1. Magnitude of a response is an unknown function of receptor occupancy.
2. Occupying all receptors may not be req to achieve EMAX--> spare receptors
3. Occupancy of a receptors binding site by diff compositions can produce diff levels of the stimulus regulating cell func --> diff in stimulus arise from diff efficacy

Front 17

1. Competitive inhibitor

2. Partial agonist

3. Full agonist with spare receptors

Back 17

1. composition that reversible occupies the binding site of a hormone that has 0 efficacy

2. occupy all receptors but fail to generate a stimulus sufficient to generate EMAX

3. hormone analogs syn to have greater efficacy than the native hormone gen stimulus sufficient to produce EMAx without occupying all receptors

Front 18

Greater efficacy does not lead to greater affinity

Back 18

partial agonist or competative antagonist may have higher affinity for a receptor than a hormone taht is full agonist with spare receptors

Front 19

Inverse agonist

Back 19

have negative efficacy
- receptor is constitutively active and addition of certain compositions converts receptor to a form not causing an effect

Front 20

Multiple effects form a single receptor type

Back 20

- binding diverese lignads some receptors can be convereted to multiple structures leading to multiple activities --> by producing multiple ligands an organism could use a single receptor type to cause diff effects

Front 21

Deviations from affinities

Back 21

1. multiple receptor types iwth inherently diff affinities
2. The formation of one hormone receptor complex change s the affinity for hormone of other unoccupied receptors --> cooperativity (+ and -)

Front 22

Cooperativity

Back 22

- no qualitative diff in appereance --> difficult to detect cooperativity using log dose response plot
- can cause susbtantial deviation from linearity in lineweaver burker or scatchard plots
- hill plot--> quantitative measure of cooperativity

Front 23

Apparent Negative cooperativity

Back 23

if hormone binds to heterogeneous population of receptors with non interacting sites with diff affinities plot of binding look like neg cooperativity even though tehres none

Front 24

Desensitization, refractoriness, tachyphalaxis

Two types

Back 24

- repeated or continuous exposure of a cell to a hormone diminishes the response to subsequent doses of the hormone
- come from a change in receptor structure or location that makes a hormone- receptor complex fail to generate a stimulus

1. homologous
2. heterologous

Front 25

1. Homologous

2. Heterologous

Back 25

1. Homologous- densensitization specific for one homorne

2. Heterologous- desnsesitization toward multiple hormones which act via distinct recepotrs but cause common effects

Consequence: pulse of a hormone to be more effective than constant dose

Front 26

supersnsitive

Back 26

if hormone signal is absent or presence of inhibitor lack of normal desensitization events may make system super sensitive to agonist

Front 27

Potentiation

Back 27

- opposing effects of desensitization
- pulse of hormone inc effectiveness of subsequent pulse

ex. hormone --> covalent modification activates enzyme and induce syn and accumulation of additional enzymes

Front 28

Atrophy

Back 28

if hormone signal that maintains machinery is absent then machinery may diminish
- takes repeated dose of hormone to restore the machinery before normal effect observed

Front 29

Synergy

1. Additive

2. Synergistic

Back 29

1. if two hormones have similar response

2. If one hormones response is more additive
- when hormones act by diff mechanisms

Front 30

Hypothalamic and pituitary hormones

Back 30

- cause effects indirectly by stimulating release of another hormone from another gland that acts on target tissue
- regulated by negative feedback loops
- permissive hormones- permit acute regulation by other hormones

Front 31

1. Primary dysfunction

2. Inappropriate relationship

Back 31

1. if elevated hormone levels arise from dysfunction of gland itself

2. measurements of hormone in normal range does not mean level is appropriate,
- if hormone is elevated effector promoting release of the horme is in normla rnage --> pathology with organ releasing the effector

Front 32

1. Hormone synthesis and storage

Back 32

- hormones stored in secretory- can be heterogenous and
variable

- release of hormones that are not stored is regulated by activation of synthetic enzymes, amt of hormone release is dependent on activation process, amt of synthetic machinery can be regulated

Front 33

2. Hormone circulation

Back 33

-enters interstitial space--> reach target tissue (cannot be bund)
- hormones bound to plasma protein --> reservoir of hormone
- gland stops making hormone, hormone leak off plasma protein --> act on tissue
- "effective" conc of hormone is frac in the free state

Front 34

3. Hormone exit form circulation to target tissue

4. Hormone activation and inactivation after release from a gland

Back 34

4. subs release form gland can be precursorof more active susbtance taht is produced by rxn taking place otuside of the gland
- rxn outside gland convert release sub to a form with less or no activity and modify it for excretion

Front 35

Measuring hormones:

Bioassay

Back 35

- crude extract on animals, isolated organs, cultured cells -> discovery and purification of many hormones

Front 36

Measuring hormones:

Physiochemical assay

Back 36

- using machines to detect unique physical and or chemical pror of hormone
- steroids or catecholamines --> derivatized --> HPLC--> fluorescence

Front 37

Measuring hormones:

Binding assays

Back 37

- antibodies bind specific hormones --> used to measure hormones
- recombinant expression of analogs of hormone receptors can be used

Front 38

Measuring hormones:

Binding assay

Dilution assay

Back 38

- molec are tagged and amt of hormone is determined by competition of the tagged hormone with untagged hormone in the sample after separation of ound from free hormone

Front 39

Measuring hormones:

Binding assays

sandwich or immuno-capture assays

Back 39

- immobilizing antibody is fized to a support and exposed to a sample
- washing waway unbound material a tagged antibody recognizing a different site on the hormone is added,
- the amt of the tagged antibody binding to the support is determined

Front 40

Measuring hormones:

Binding assays

Radioimmune or radioreceptor

ELISA

Back 40

-tag is radioactive the assay is a radio assay


-enzyme that generates a spectophoto-metrically-detected product then the assy is termed ELISA (enzyme linked immuno spectophotometric assay

Front 41

Estimating hormone production

Back 41

1. measure the venous- arterial difference in hormone concentration
2. measure plasma turnover of the hormone (inject radioactive tracer)
3. Measure urinary excretion in product (estimate of avg circulating levels of homrones)

Front 42

While a constant concentration of a ligand may permit other mechanisms to regulate a function,

Back 42

unless the concentration of the ligand changes no information is transmitted and the ligand is not regulating a function
- regulation may arase not just from amplitude of change but from patern of change

Front 43

1. Amplitude modulation

2. Frequencey modulation

3. Oscillation

Back 43

1. magnitude of a change in hormone concentration

2. rate of change and pattern of pulses

3. a regular pattern of inc and dec of a hormone, effectiveness may req a particular freq of oscillation of hormone concentration

Front 44

Endocrine pathologies

Back 44

1. Subnormal hormone production
2. excessive hormone production
3. Production of abnormal hormones
4. Resistance to hormone action
5. Altered release, transport, or degradation of hormones