Endocrine control mechanism

From Iusmphysiology

Current revision as of 21:18, 21 March 2011

• 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.