Endocrine control mechanism
From Iusmphysiology
- started here on 03/01/11 at 11AM.
[edit] Endocrine control mechanisms
[edit] 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.
[edit] Properties of hormones
- See slide.
[edit] 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.
[edit] Cartoon
- Just shows that endocrine is indirect
[edit] Cartoon
- Paracrine, autocrine, endocrine.
- Juxtacrine: membrane proteins of neighbors communicate.
- Brain is a major endocrine gland.
[edit] Peptide and protein hormones
- Insulin, growth hormones, glycoproteins
- Presequence is cleaved
- Then prosequence is cleaved
- Then the hormone is generated.
- Think ACTH.
[edit] Structure map
- We are not supposed to know all that.
[edit] 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).
[edit] Endocrine map
- Not tested.
- Many developmental diseases result in loss of endocrine tissue or fxn.
[edit] Hormone stimuli and responses
- ?
[edit] Hormone transport
- Sometimes carrier protein carry hormones.
- General rule:
- Amines, peptides, and proteins travel free
- Steroids, and thryoid hormones travel bound
- This makes sense because steroids and thyroids are structurally very similar.
- There are exceptions:
- Insulin like growth factors are proteins but have specific binding proteins.
[edit] Hormone metabolism, degradation, and excretion
- Carrier proteins can change the 1/2 life.
- MCR is the inverse of the 1/2 life.
[edit] Peripheral transformation
- Most of the thyroid production is T4, but the active molecule is T3.
- So one of the iodides 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 female baby
[edit] Endocrine diseases
- Causes:
- Lack of hromones (enzyme or gene missing)
- Lack of receptor
- Too much hormone
- Lack of control mechanism
- Other hormones having a deleterious effect
[edit] Endocrine control systems
- Hypothalamus -> TRH -> ant pit (thyrotrope) -> TSH -> thyroid (follicular cells) -> t3, t4 -> repress TSH release at the ant pit (thyrotropes).
- 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
[edit] Specificity
- There is very high specificity in hormone receptors.
- Estrogen and testosterone look very similar as do their receptors.
[edit] Signaling pathways
- Remember that not all pathways amplify the signal.
[edit] Ab-based hormone assays
[edit] 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 ?
[edit] 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.
- The sandwhich assay can asses biological functioning levels of the signal.
[edit] 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.
- Arginine can cause a child to dump the pit's reservoir of growth homrone, but even that response is variable among people.
[edit] Pituitary gland
- Controls: growth, metabolism, reproduction, stress response, lactation
- Used to be called the master gland
- Not really true b/c brain regulates the pit
- But the pit does control many other organs
[edit] DEvelopment
- Many pit diseases have their origin in dysfunctional development.
- The pit is a composite 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.
- The pituitary gland has two origins (oral ectoderm and neuoectoderm)
- Oral ectoderm
- Generates the adenohypophysis
- Forms three 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)
[edit] Hypothalamus-Ant Pit axis
- Brain makes hormones, control ant pit via protal vessels
- Ant pit makes it's own hormones and sends them systemically.
[edit] Ant pit hormones
- Any cell that makes one of these have names
- GH
- PRL
- ACTH
Get the others
[edit] 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.
[edit] 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.
[edit] 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.
[edit] Post-pit associated diseases
[edit] 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.
[edit] Syndrome of inappropriate ADH secretion (SIADH)
- Over secretion of ADH
- Can be caused by anaesthetics, 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.
