Endocrine control mechanism

From Iusmphysiology

(Difference between revisions)
 
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*started here on 03/01/11 at 11AM.
*started here on 03/01/11 at 11AM.
 +
==Endocrine control mechanisms==
==Endocrine control mechanisms==
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**Used to say: small size but we don't use this any more b/c of gut and adipose, etc.
**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).
*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===
===Endocrine map===
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**Amines, peptides, and proteins travel free
**Amines, peptides, and proteins travel free
**Steroids, and thryoid hormones travel bound
**Steroids, and thryoid hormones travel bound
 +
***This makes sense because steroids and thyroids are structurally very similar.
*There are exceptions:
*There are exceptions:
**Insulin like growth factors are proteins but have specific binding proteins.
**Insulin like growth factors are proteins but have specific binding proteins.
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===Peripheral transformation===
===Peripheral transformation===
*Most of the thyroid production is T4, but the active molecule is T3.
*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.
+
**So one of the iodides must get ripped off to make it active.
-
*TEstosterone is active
+
*Testosterone is active
-
**Can be converted to dihydrotest via 5 alpha reductase that has separate, important roles (DHT).
+
**Can be converted to dihydrotest via '''5 alpha reductase''' that has separate, important roles (DHT).
-
*DHT associated with Male pattern baldness
+
*DHT associated with male pattern baldness
**Propecia converts test to dht
**Propecia converts test to dht
-
**Bad for pregnant women: ambiguous genitalia, and dev issues for male baby
+
**Bad for pregnant women: ambiguous genitalia, and dev issues for female baby
===Endocrine diseases===
===Endocrine diseases===
*Causes:
*Causes:
-
**Lack of hromones (enzyme or gen missing)
+
**Lack of hromones (enzyme or gene missing)
-
**lack of receptor
+
**Lack of receptor
**Too much hormone
**Too much hormone
**Lack of control mechanism
**Lack of control mechanism
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===Endocrine control systems===
===Endocrine control systems===
-
*Ant pit -> tsh -> thyroid -> t3, t4 -> repress tsh release at the ant pit.
+
*Hypothalamus -> TRH -> ant pit (thyrotrope) -> TSH -> thyroid (follicular cells) -> t3, t4 -> repress TSH release at the ant pit (thyrotropes).
**Neg feedback
**Neg feedback
*Suckling at nipple -> neuro signal -> brain -> post pit -> oxytocin -> milk ejecation at breast -> more suckling
*Suckling at nipple -> neuro signal -> brain -> post pit -> oxytocin -> milk ejecation at breast -> more suckling
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*Second ab can bring in radioactivity or color or enzyme
*Second ab can bring in radioactivity or color or enzyme
*These diagnostics are highly automated.
*These diagnostics are highly automated.
 +
*'''The sandwhich assay can asses biological functioning levels of the signal.'''
===Assays in diagnostic medicine - problems===
===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.
*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.
*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.
+
*Arginine can cause a child to dump the pit's reservoir of growth homrone, but even that response is variable among people.
==Pituitary gland==
==Pituitary gland==
*Controls: growth, metabolism, reproduction, stress response, lactation
*Controls: growth, metabolism, reproduction, stress response, lactation
-
*Used to be called the mastergland
+
*Used to be called the master gland
**Not really true b/c brain regulates the pit
**Not really true b/c brain regulates the pit
**But the pit does control many other organs
**But the pit does control many other organs
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===DEvelopment===
===DEvelopment===
*Many pit diseases have their origin in dysfunctional development.
*Many pit diseases have their origin in dysfunctional development.
-
*The pit is a composit gland
+
*The pit is a composite gland
**Comes from the developing ventral brain
**Comes from the developing ventral brain
**Comes from the rahke's pouch in the roof of the developing mouth
**Comes from the rahke's pouch in the roof of the developing mouth
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-
*Two origins: both ectodermal
+
*The pituitary gland has two origins (oral ectoderm and neuoectoderm)
*Oral ectoderm
*Oral ectoderm
**Generates the adenohypophysis
**Generates the adenohypophysis
-
**Forms two sections:
+
**Forms three sections:
-
**pars tuberalis  
+
***pars tuberalis  
-
**pars distalis (anterior lobe) and  
+
***pars distalis (anterior lobe) and  
-
**pars intermedia (intermediate lobe)
+
***pars intermedia (intermediate lobe)
-
***Very small in humans
+
****Very small in humans
*Neurohypophysis
*Neurohypophysis
**Three parts:
**Three parts:
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*Any cell that makes one of these have names
*Any cell that makes one of these have names
*GH
*GH
-
**
 
*PRL
*PRL
*ACTH
*ACTH
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====Syndrome of inappropriate ADH secretion (SIADH)====
====Syndrome of inappropriate ADH secretion (SIADH)====
*Over secretion of ADH
*Over secretion of ADH
-
*Can be caused by anasesthetics, drugs, tumors, smoking.
+
*Can be caused by anaesthetics, drugs, tumors, smoking.
*Can be mild to severe
*Can be mild to severe
**Severe -> coma and death
**Severe -> coma and death

Current revision as of 21:18, 21 March 2011

  • started here on 03/01/11 at 11AM.


Contents

[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)


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