Download EN-1-27-99

Endocrine
(1-27-99)
1st quiz is next week:
20-25 questions
1st hour in the gym
1st assigned chapter + class info
You need baseline information on the endocrine system so that you can understand the
other things
Interdependence of systems (see last week0
Ex – hypothalamic-pituitary-thyroid axis
Concepts of: feedback
Turn-on/turn-off
Other systems use a similar mechanism, just different hormones
Innate mechanisms
Important for understanding disease
Ex – signs and symptoms
If the endocrine system operates normally, you don’t see any consequences
If it doesn’t, you see consequences (signs and symptoms)
Usually due to an abnormality in hormone concentration
1)
2) Why is the hormone concentration increased?
How hormones work:
Peptide hormones
synthesized as parts of larger protein molecules and processed as secretory proteins
act via receptors located in the cell membrane with the recognition/binding site
exposed on the cell surface and the activity domain facing the inside of the cell
receptors provide a sophisticated mechanism of controlling hormone activity
ex – if no receptor, the activity of the hormone is negated
receptors are proteins that have structural and functional integrity
receptors have two essential functional characteristics
1) a recognition site, which binds the hormone with high specificity and affinity
2) an activity site, which transduces the information received into a biochemical
message
recognition of the hormone is controlled by a number of things:
ex – like an enzyme recognizing its substrate
depends on the tertiary and quaternary structure
if the receptor doesn’t recognize the hormone, there is no interaction
activity - ?? nothing said
Fig 199-2: shows different receptor structures
QQ: What if he gave us this diagram and asked us to fill in the blanks
Allosteric receptor proteins:
Adopt various conformation
Binding of the hormone ligand results in the active configuration
If not bound to the hormone, the receptor is in its inactive configuration
Getting a hormone to bind to its target cell:
Depends on the concentration of the hormone
Depends on the concentration of the receptors
Depends on the affinity of the receptors
Quantitative: depends on the #s of receptors and hormone
Qualitative: depends on the effect of affinity/avidity (the tightness of binding)
Also – how likely the hormone is to bind to its receptor
Ways to increase reaction:
Heat the mixture (to increase the # of interactions)
Modify the receptor so it binds more tightly/loosely
Modify the #s of hormone and receptor
QQ: Factors that control the concentration of both the hormone and the receptor
determine the biologic responses of cells, of organs, and of the whole organism.
Ex – Q – The concentration of the receptor is just as important as the concentration
of the hormone. (true/false)
TSH and T4 – lag period
would get fluctuations if the only method of control was concentration
actually, fluctuations are not clinically significant due to receptor responses
can alter quality (affinity) faster than you can alter quantity
can change receptor #s faster than hormone #s
(a lot of Nobel prizes have been given for work done on receptors)
some people lack receptors that recognize LDLs
their cholesterol levels stay high, no matter what they do
so – genes are more important than diet when it comes to cholesterol
rate-determining factor for cholesterol control
LCAT – hepatic enzyme that degrades cholesterol (happens intracellularly)
LDL carries most of the cholesterol
Binds to LDL receptors and is brought into the cell
Some people lack LDL receptors
SOL when it comes to endogenous cholesterol
Exercise:
enhances cholesterol utilization
Tends to qualitatively improve the function of LDL receptors
And increase their #s (get more receptors per cell)
Innate – protects you from you
Receptor protein: recognizes anything that will fit with it
If you alter its shape, it can’t interact
To alter a reaction: Alter the hormone concentration
Alter the relative concentrations of hormone and receptor
Receptor regulation:
Up regulation
Down regulation
Some people appear to be euthyroid (‘normal’ thyroid) when they actually have
decreased thyroid hormone
How?
By increasing the #s of their receptors
Up regulation:
If you decrease hormone concentration, it tends to increase the # of receptors
If there are a lot of receptors, it increases the probability of the hormone finding a
receptor, and acts as if you had normal levels of the hormone, even though you
actually have low levels
Down regulation:
If you increase hormone concentration, the number of receptors decreases
Up/down regulation
helps smooth out target cell activity in the face of hormone fluctuations
why do the #s of receptors change?
Supply and demand  receptor sequestation
Hormone ligands and receptors bind with high affinities (equilibrium dissociation
constants [KD] of nanomolar to picomolar), thus providing the specificity necessary for
cells to decode the information provided by the low concentration of hormone present
among the many other circulating and extracellular proteins.
Also – abnormalities in the receptor
Endocrine pathology:
8 basic mechanisms
hypofunction: usually decreased concentration or decreased hormone effect
hyperfunction: usually increased concentration or increased hormone effect
anemia: not a cause but a response/result of something
ditto for hyper/hypo
ex – hyperthyroid (too much TH)
ex – thyroid gland producing too much
functional tumor
hyperplasia (increased # of cells)
ex – trying to compensate for something else
hyper: could have elevated ectopic production of the pre-hormone
exogenous source of the hormone
ex – Cushing’s – can get this if take cortisol over a long period
not destroying it fast enough (blocked degradation)
enhanced activity on the target cell
hypo:
destroyed the gland
blocked/inhibited the synthesis of the hormone
ex – genetic defect
metabolic toxins
analogs
messed up conversion of pre-hormone to hormone
enhanced degradation of the hormone
decreased action at the target cell
antagonists
Graves’ – hyperthyroid
Antibodies bind to TSH receptors and produce more TSH
(act as agonists)
Hashimoto’s – hypothyroid
Antagonists block TSH from binding
Modes of action:
Steroid hormones:
Synthesized from precursor cholesterol
This group acts via structurally related receptors that bind to DNA receptor sites
to regulate transcription of target genes.
Peptide hormones:
Membrane receptors
Biologic amplification and 2nd messengers
Ex – 1 molecule  25 responses
2nd messenger:
once the hormone binds and the message is passed on, you don’t need the hormone
anymore
activation site turns on the 2nd messenger
2nd messenger does the amplification
ex: cAMP: turns on protein kinases via phosphorylation
Ca
Mg
Tyrosine phosphate
Diesteryl __??__
Beta blockers: Used for blood pressure and coronary artery dilation
Block adrenergic receptors
Antagonist
 calming effect
Stimulators:
amphetamines, …
Steroid: receptors are intracellular
(in the cytoplasm or the nucleus)
receptors actually transport the message to the cell’s DNA
thyroid hormone: needs a receptor
carrier proteins: __??__