Editing Endocrine control mechanism

*started here on 03/01/11 at 11AM.

==Endocrine control mechanisms==

===Endo signaling===
*It is indirect; goes through the blood stream.
*Specificity is defined by target cells having the appropriate receptors.
*There are many feedback mechanisms to maintain homeostasis.

===Properties of hormones===
*See slide.

===Hormones have varied chemical structures===
*Can be amines, polypeptides (nasal sprays), proteins (must be injected), thyroid hormones, steroids, arachidonic acid derivatives (e.g. prostaglandins)
*Chemical structure determines deliverability.

===Cartoon===
*Just shows that endocrine is indirect

===Cartoon===
*Paracrine, autocrine, endocrine.
*Juxtacrine: membrane proteins of neighbors communicate.
*Brain is a major endocrine gland.

===Peptide and protein hormones===
*Insulin, growth hormones, glycoproteins
*Presequence is cleaved
*Then prosequence is cleaved
*Then the hormone is generated.
*Think ACTH.

===Structure map===
*We are not supposed to know all that.

===Endocrine glands===
*Old view has only 7 but we now know that many tissues secrete many hormones.
*For example, adipose releases laptin and such.
*Also, GI releases hormones ("a gut feeling").


*Glands:
**Ductless
**Secrete hormones
**Well perfused (to receive and respond to signals)
**Respond to regulatory signals
**Have diverse embryological origins
**Used to say: small size but we don't use this any more b/c of gut and adipose, etc.
*This list is true, but there are some organs that are composite so they may have additional features (like the pancreas has ducts b/c it has another fxn).


===Endocrine map===
*Not tested.
*Many developmental diseases result in loss of endocrine tissue or fxn.

===Hormone stimuli and responses===
*?

===Hormone transport===
*Sometimes carrier protein carry hormones.
*General rule:
**Amines, peptides, and proteins travel free
**Steroids, and thryoid hormones travel bound
*There are exceptions:
**Insulin like growth factors are proteins but have specific binding proteins.

===Hormone metabolism, degradation, and excretion===
*Carrier proteins can change the 1/2 life.
*MCR is the inverse of the 1/2 life.

===Peripheral transformation===
*Most of the thyroid production is T4, but the active molecule is T3.
**So one of the iodines must get ripped off to make it active.
*TEstosterone is active
**Can be converted to dihydrotest via 5 alpha reductase that has separate, important roles (DHT).
*DHT associated with Male pattern baldness
**Propecia converts test to dht
**Bad for pregnant women: ambiguous genitalia, and dev issues for male baby

===Endocrine diseases===
*Causes:
**Lack of hromones (enzyme or gen missing)
**lack of receptor
**Too much hormone
**Lack of control mechanism
**Other hormones having a deleterious effect

===Endocrine control systems===
*Ant pit -> tsh -> thyroid -> t3, t4 -> repress tsh release at the ant pit.
**Neg feedback
*Suckling at nipple -> neuro signal -> brain -> post pit -> oxytocin -> milk ejecation at breast -> more suckling
**Positive feedback
**Stops when baby stops suckling
*Inhibitory release by brain, like prolactin being under constant repression
**Inhibitory control
*Enzyme action at a certain place converts a hormone to active form
**Metabolic control
*GIP on pancreas
**Feedfoward control

===Specificity===
*There is very high specificity in hormone receptors.
*Estrogen and testosterone look very similar as do their receptors.

===Signaling pathways===
*Remember that not all pathways amplify the signal.

===Ab-based hormone assays===

====RIA====
*A competition assay:
**Known amount of radioactive hormone
**Unknown amount of unlabeled hormone
**Ab for target hormone you are trying to measure
*The more unlabeled hromone in sample, the more radiation displaced.
*Use a curve to determine concentration.
*Highly specific.
*Does not correlate to biological activity.
*Experiments are calibrated so that important samples land on the steep, straight part of the curve.
**IMprt b/c small changes in sample give big changes in radioactivity.
**Impt b/c ?

====Sandwhich assay / immunometric analysis====
*Faster and more sensitive than RIA.
*Second ab can bring in radioactivity or color or enzyme
*These diagnostics are highly automated.

===Assays in diagnostic medicine - problems===
*Assays may not be comparable across locations b/c of different protocols, storage methods, biological variability, temporal differences in hormone production.
*Pharma can change them, too, via contraception, etc.
*Arginin can cause a child to dump the pit's reservoir of growth homrone, but even that response is variable among people.

==Pituitary gland==
*Controls: growth, metabolism, reproduction, stress response, lactation
*Used to be called the mastergland
**Not really true b/c brain regulates the pit
**But the pit does control many other organs

===DEvelopment===
*Many pit diseases have their origin in dysfunctional development.
*The pit is a composit gland
**Comes from the developing ventral brain
**Comes from the rahke's pouch in the roof of the developing mouth
***Moves up and becomes associated with base of brain
**Then sphenoid bone grows to separate pouch from mouth.


*Two origins: both ectodermal
*Oral ectoderm
**Generates the adenohypophysis
**Forms two sections:
**pars tuberalis 
**pars distalis (anterior lobe) and 
**pars intermedia (intermediate lobe)
***Very small in humans
*Neurohypophysis
**Three parts:
**Median eminence
**Infandibular stalk
**Posterior lobe (pars nervosa)

===Hypothalamus-Ant Pit axis===
*Brain makes hormones, control ant pit via protal vessels
*Ant pit makes it's own hormones and sends them systemically.

===Ant pit hormones===
*Any cell that makes one of these have names
*GH
**
*PRL
*ACTH
 Get the others

===Hypothalamus-Post Pit axis===
*Here the brain makes the hormones and delivers them directly
*Cell bodies in the hypothalamus are neruons.
**Nerve endings pass through stalk to the posterior pit
**Makes some hormones
***Post pit is truly an extension of the brain
*Post pit
**Make vasopressin and ADH
 Missed some stuff including magnocenter


*stopped here on 03/01/11 at 12PM.
*started here on 03/02/11 at 11AM.


*He skipped some slides on vasopressin and such.


===Diagnosis of endocrine diseases===
*Have to look for the signals in the pathway axis.
*Determine what is high or low and what receptors are present or not.
*Look at the results (short stature, etc.) and work through the pathway.

===Treatment of endocrine diseases===
*Ask yourself if the hormone or receptor can be bypassed by intervening downstream.
*If the final receptor is missing then you're in a tough place.

===Post-pit associated diseases===

====Diabetes insipidus====
*This is a disease of lack of action.
*When vasopressin doesn't work at the kidney, you get diabetes insipidus.
*Increased thirst (polydipsia) and urination (polyuria).
*Central DI: mutated gene so hormone isn't made.
**Tx with pills or nasal sprays to replace the AVP. 
*Peripheral DI: mutation in receptor or a problem with aquaporin such that kidney doesn't work
**Give drug that increases kidney tubule sensitivity to AVP
**Harder to treat than central DI.

====Syndrome of inappropriate ADH secretion (SIADH)====
*Over secretion of ADH
*Can be caused by anasesthetics, drugs, tumors, smoking.
*Can be mild to severe
**Severe -> coma and death
*Tx:
**Mild: control water intake
**severe: kill some kidney function and thus induce the opposite disease
***This is a common trend in endocrine disorders: fix one extreme by making the pt in the other extreme (which can be treated)


*Moved on to [[Adrenal gland]] on 03/02/11 at 11:11AM.