Are hormones involved in regulating''

1
Are hormones involved in regulating..

• Your elevated heart rate when you heard about
  this mornings pop quiz?
• Feeling thirsty?
• A hen incubating her eggs?
• A hungry chick begging?
• A salmon dying after spawning?
• A sparrow attacking his reflection in the window?
• Jetlag?
• Going into labor?
• Low blood sugar?
• Increased calorie burning in response to cold
  temperature?
• How quickly young animals grow?

2
Are hormones involved in regulating..

• Your elevated heart rate when you heard about
  this mornings pop quiz? YES (catecholamines)
• Feeling thirsty? YES (AVP, aldosterone)
• A hen incubating her eggs? YES (progesterone)
• Hungry chicks begging? YES (corticosterone)
• A salmon dying after spawning? YES
  (corticosterone)
• A sparrow attacking his reflection in the window?
  YES (testosterone)
• Jetlag? YES (melatonin)
• Going into labor? YES (oxytocin)
• Low blood sugar? YES (insulin glucagon)
• Increased calorie burning in response to cold
  temperature? YES (thyroxine)
• How quickly young animals grow? YES (IGFs)

3
Why hormones are great to study

• Involved in control of pretty much EVERY
  physiological system
• Most common way external or internal cues are
  converted into a physiological or behavioral
  response
• Very elegant and effective way to communicate
  within an organism
• You can study them without killing anything!

4
Functions of the endocrine system

• Maintain Internal Homeostasis
• METABOLISM
• OSMOREGULATION
• Regulate Growth and Morphological change
• Coordinate Development
• Coordinate Reproduction
• Facilitate Behavioral and Social interactions
• The primary function of many hormones is to
  stimulate release of other hormones (called
  tropic and releasing hormones)!

5
Endocrine system vs. Nervous system

• Both use chemical secretion to conduct
  information.
• Major difference mode specificity of delivery
  to intended receiver
• Nervous system telephone signal goes
  straight from sender to receiver along closed
  lines (axons). Rapid!
• Endocrine system radio signal broadcast
  generally (in bloodstream), only receivers with
  the properly tuned hardware (receptors) can
  receive it. Slower.

6
Players in the endocrine system

• Endocrine glands
• Hormones
• Receptors
• Binding globulins
• Target tissues

7
Endocrine glands

• In the brain
• Hypothalamus
• Pituitary
• In the rest of the body
• Adrenal glands
• Gonads (testes and ovaries)
• Pancreas
• Thyroids
• Liver

8
So what are hormones?

• Molecules secreted by specialized glands that
  function as a message within an organism their
  only function is to convey information.
• Travel from site of production (endocrine cell)
  to site of action (target tissue) via blood
• Operate by binding to specific receptors only
  expressed at target cells

9
So what are hormones?

• Not all chemical messengers are hormones!
• Chemical signals WITHIN cells not hormones
• Chemical signals like ions have effects but dont
  act via receptors
• Several categories of hormones, most commonly
  classified by molecular structure
• Steroid
• Protein (peptide glycoprotein)
• Structure has major implications for where and
  how hormones work!

10
Hormone Receptors

• Receptors are proteins that bind a hormone at one
  site and initiate cellular activity at another
• Their function is to make sure the appropriate
  cells respond to the appropriate hormones in the
  appropriate way.
• Receptors are characterized by 3 things
• Affinity how tightly it binds to a particular
  molecule
• Specificity how much it prefers to bind one
  molecule over other
• Capacity how many ligand molecules it can bind
  at a time (usually just 1)

11
Hormone Receptors

• Question Which combination would be best for an
  effective receptor?
• High affinity, low specificity
• Low affinity, low specificity
• High affinity, high specificity

12
Hormone Receptors

• Question Which combination would be best for an
  effective receptor?
• High affinity, low specificity
• Low affinity, low specificity
• High affinity, high specificity
• You want receptors to only be bound/activated by
  the hormone of interest (high specificity) and
  you generally want them to grab ahold tightly
  (high affinity) to induce your effect and be
  sensitive to low levels of hormone

13
Hormone Receptors (cont)

• Receptors are classified by their locations
• 1) Membrane receptors - Embedded in the cell
  membrane
• Span the phospholipid bilayer
• Hormone binds extracellularly
• Binding alters receptor conformation, transmits
  intracellular signal (those famous G-proteins!)
• 2) Cytosolic and nuclear receptors - in the
  cytoplasm or nucleus (genomic)
• Activated receptor binds to DNA and
  initiates/alters gene transcription
• Hormone must enter cell first

14
Hormones Characteristics of hormone families

• Structure
• Synthesis
• Storage Secretion
• Transport
• Mechanisms of Action
• Structure defines the 2 major classes
• Protein hormones
• Steroid hormones

15
Protein and peptide hormones

• Structure
• Amino acid chains
• Sequence
• Folded structure
• Can be long or VERY short (lt10aa!)
• Hydrophilic (water soluble)
• Cannot cross cell membranes! (ie no passive
  diffusion)

16
Protein and peptide hormones

• Synthesis
• Begins with activation of gene transcription to
  mRNA
• mRNA leaves nucleus, binds ribosome, relocated to
  endoplasmic reticulum (ER)
• (note lots of RER in protein hormone producing
  cells!)
• Protein is translated into ER (signal sequence)
• Translational product moves through ER and golgi,
  modified (cleavage, glycosylation,
  phosphorylation etc)

17
Protein hormone synthesis
18
Prohormones (protein hormone precursors)
Preprohormone
Signal peptide
Prohormone
Inactive fragment

• Permits fine-tuning of hormone activation
• Prohormone -gt active hormone requires an addition
  enzyme that can be localized around target tissue

19
Protein hormones

• Storage/Secretion
• Can be stored in vesicles (or granules)
• After synthesis and modification, ends up at the
  end of the golgi
• Pinches off into either secretory or storage
  vesicles
• In reponse to proper signal, will be released
  from cell by exocytosis
• Question why might it be useful to be able to
  store hormones until they are needed?

20

• Question why might it be useful to be able to
  store hormones until they are needed?

21

• Question why might it be useful to be able to
  store hormones until they are needed?

Answer Protein synthesis takes time! Storage
allows immediate release when needed
22
Protein hormones

• Mechanisms of action
• Proteins bind to membrane receptor
  extracellularly
• Binding induces conformational change in
  intracellular part of receptor
• Newly exposed site interacts with internal
  proteins, initiates cascade of intracellular
  messengers
• Often results in
• Activation or inactivation of enzymes via
  phosphorylation or dephosphorylation
• Opening of ion channels
• Many peptide hormones serve to trigger release of
  more hormones from target tissue!

23
Membrane Receptors
Ligand-binding domain
extracellular
cell membrane
intracellular
Site that interacts with internal proteins
24
Active enzyme
Unoccupied receptor
25
Summary for protein hormones

• Cant move through membranes
• Synthesized like other proteins
• (DNA, mRNA, ribosomes, RER, golgi)
• Bind extracellular receptors
• Receptors interact with proteins inside cell,
  initiate cell-signaling cascades

26
Steroid hormone structure
Precursor to ALL steroid hormones

• Small molecules carbon ring structure
• Lipid soluble (hydrophobic)
• Pass easily through cell membranes
• Tiny differences alter function entirely!

27
Steroid hormone synthesis

• Always starts with cholesterol (27 carbons)
• Series of enzymes alter steroids, but maintain
  fundamental ring structure.
• Cholesterol synthesis occurs in smooth ER and
  enzymatic conversion occur in mitochondria
• Steroid families classified by the number of
  carbons in the molecules

28
Steroid hormone synthesis

• Example androgen synthesis
• Enzyme names usually describe their effect on the
  substrate
• Almost all precursors are active hormones
  themselves!
• Question How could you ensure that you have the
  proper steroid at the proper target tissue?

29
Steroid hormone synthesis

• Question How could you ensure that you have the
  proper steroid at the proper target tissue?
• Answer Localize expression of enzymes!

30
Steroid hormone storage/secretion

• Cant be contained by cell membranes, therefore
  cant really be stored!
• Secreted as its produced (constituitive
  secretion) rather than being released in
  response to stimulus (regulated secretion)
• Requires 3-5 min. from stimulus to detectable
  increase in plasma

31
Steroid Hormone TransportBinding Globulins

• Summary binding globulins help transport
  hormones and regulate the amount that is
  biologically active.
• Steroid hormones often travel through blood bound
  to large proteins or globulins
• This helps them arrive at target tissues and not
  diffuse prematurely out of blood into the wrong
  tissues
• Hormones bound to globulins cannot be broken
  down, but they are also biologically inactive
  until released.
• Thus bound they cannot trigger physiological
  responses.
• However, having a lot of steroid bound to
  globulins means that one way to rapidly increase
  steroid release is to downregulate globulin
  levels at target tissues
• May function as a temporary storage mechanism

32

• Steroid crosses cell membrane into cytoplasm
• Steroid binds cytosolic receptor which is kept
  inactive by heat-shock proteins (HSPs)
• Binding alters receptor confirmation, releasing
  HSPs
• Hormone-bound receptors, in the absence of HSPs,
  are free to enter nucleus
• Active receptors bind directly to DNA and
  initiate transcription
• mRNA enters cytoplasm and a new protein is
  synthesized!

Steroids Mechanisms of Action
33
Question Hormone synthesis

• How does this illustrate protein hormone
  synthesis?
• How does this illustrate steroid hormone
  synthesis?

34
Question Hormone synthesis

• How does this illustrate protein hormone
  synthesis?
• How does this illustrate steroid hormone
  synthesis?
• Both entail protein translation. Main difference
  is that the translation product is the hormone
  itself for protein hormones.
• But for steroids, the translation product will be
  the ENZYMES that modify chlesterol to make the
  hormone.

35
Feedback loops

• Positive Feedback Hormones stimulate each other,
  product of target cell increases production of
  initial hormone which causes even more secretion
  of the target cell product
• Tend to be rare and shortlived because they can
  quickly get out of control!
• Negative feedback
• Short- and long-loops.
• Product inhibits further production of self and
  of stimulating hormone.
• Can operate on multiple levels.