Endocrine control mechanism

From Iusmphysiology

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Revision as of 16:57, 1 March 2011

• started here on 03/01/11 at 11AM.

Contents 1 Endocrine control mechanisms 1.1 Endo signaling 1.2 Properties of hormones 1.3 Hormones have varied chemical structures 1.4 Cartoon 1.5 Cartoon 1.6 Peptide and protein hormones 1.7 Structure map 1.8 Endocrine glands 1.9 Endocrine map 1.10 Hormone stimuli and responses 1.11 Hormone transport 1.12 Hormone metabolism, degradation, and excretion 1.13 Peripheral transformation 1.14 Endocrine diseases 1.15 Endocrine control systems 1.16 Specificity 1.17 Signaling pathways 1.18 Ab-based hormone assays 1.18.1 RIA 1.18.2 Sandwhich assay / immunometric analysis 1.19 Assays in diagnostic medicine - problems 2 Pituitary gland 2.1 DEvelopment 2.2 Hypothalamus-Ant Pit axis 2.3 Ant pit hormones 2.4 Hypothalamus-Post Pit axis

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