Lecture 8-12 Flashcards
Hormones function (4)
- reproduction
- Growth and development
- Maintanence of internal environment (homeostasis)
- Energy production, utilization and storage
The nervous system and endocrine glands are interrelated, how?
- In general, nervous system controls the more rapid activities, the endocrine system regulates the slower functions
Definition of hormone
- Chemical messengers produced by one cell to regulate activity of another cell (target) and delivered by means of endocrine, neuroendocrine, paracrine, autocrine, neurocrine, or pheromonal route
Endocrine + ex (2)
- The hormone is released into the circulation and is transported to the target cell by blood vessels
- Ex: Gonadotropin hormones secreted from pitutary (target tissue = testis/ovary)
Neuroendocrine (3)
Diff + what + ex
- Same as endocrine but secretatory cell is a neuron
- The hormone is released by nerve cells into the circulation and is transported to the target cells
- Ex: Vasopressin is secreted by hypothalamic neurons via pituitary -> target tissue kidney and vascular smooth muscles
Paracrine + ex (3)
location + what + ex
- Secretatory cell is quite close to target tissue
- The hormone is released and diffuses to it’s target cell through the immediate extracelllular fluid
- Ex: many growth factors such as epidermal growth factor -1
Autocrine (2)
what + ex
- The target of the secreted hormone is the same cell that released it
- ex: Prostaglandins and some growth factors
Neurocrine + ex (2)
- neurons secrete the hormone in the immediate vicinity of the target cell
- Ex: neurotransmitters such as norepinephrine and dopamine
Hormones can be delivered via
Multiple ways!
Pheromone + ex (2)
+ also called….
- The hormone is released into the environment to induce a biological response in another animal. It is usually species specific and may also be called exocrine action
- ex: reproductive pheromones in mammals, fish and insects. Fish females produce eggs in water and male male release sperm.
Molecules involved in information transfer include (4) :
INCLUDE EXAMPLE + detailss!!
- Peptides and proteins (Transcription-> precurrsor-> cleave for active)
- Steroids (androgens, estrogens, progestogens, corticosteriods): derived from cholesterole
- Amino acids (GABA) and amino acid derivatives (thyroid hormones/iodothronines and catecholamines)
- Eicosanoids (arachondonic acid and phospholipid derived): ex: prostaglandins, prostacyclins
Hormones interact with their target cells by binding to —– molecules, termed —–
- specific
- receptors
Hormone specificity is achieved by ….
requires?
- A lock and key mechanism, activation require correct shape and charge (right area for receptor to be activated)
Recptors have 2 functions:
- Recognition: Specific binding
- Transduction of signal
Agonists
Coumpounds/hormones that bind to receptor to stimulate biological activity
Competitive antagonists (2)
What + structure… + competes
- Molecule that fits in the pocket of receptor but becaus it lacks appropriate charges, it will not stimulate biological response. Occupies pocket and blocks the binding site.
- Similar structure but different charge
- Competes for binding site
Ligand
Anything that binds to a receptor
ex: hormones
Allosteric antagonist
Change conformation, bind not at active site
Hormone-receptor interaction is —- and —-
rapid
reversible
Association rate constant (3)
symbol + units + funcion
- K+1
- M^-1 sec^-1
- Function of time
Dissociation Rate constant
symbol + units + funcion
- K-1
- Function of time
- sec^-1
iatio
Ratio of K+1 and K-1
K+1/K-1
Symbol + name + what occurs here + function + units +known as
Ka
- Equilibirum association constant
- Hormones when secreted, reaches a plateau at equilibirum, for every one that binds, the one dissociates
- At equilibrium, constant amount of receptor bound
- not a function of time
- M^-1 (L per mole)
- Known as affinity, higher affinity, more potent, less dosage, less side effect
Reciprical of Ka
1/Ka
What its called + units
- Kd: Equilibirum dissociation constant
- M unit (Moles /L)
When K+1 is greater that means…
Ka + affinity + the hormone….
- Ka is greater
- Affiinity is greater
- Binds faster, dissociate slower
ED50 (3)
What + measure of + function of
- ED50 is the effective dose giving half maximal response. It is a measure of hormone potency and is a function of receptor affinity + structure
Higher affinity you get — Kd and —– ED50
- lower
- lower (you illcit same level of response at lower doses)
DRC curve shift to the left then….
ED50 + affinity
- Lower ED50
- Higher affinity
In DRC curve, adding hormones, reaches plateau from biological response (maximal response) and this is a function of ——
receptor density (# of receptors)
Receptor binding affinity and capacity are regulated by a variety of physiological and pharmacological factors (2):
- Increased receptor synthesis and avaliability = upregulation (increase hormone responsiveness)
- Decreased receptor synthesis and avaliability = downregulation
Receptor # can change but does not mean that ED50 —-
- change
- ED50 is an affinity, usually only confromation changes that affects affinity
Hormone affinity is a function of
receptor affinity
Maximal response is a function of
receptor #
DRC curve: Decreased in inifinity AKA Sensitivity (3)
Curve + [] + recptor/ED50
of receptor is the same, new ED50 is now 10 fold lower.
- Curve will shift to the right
- More hormone + ligand to illicit same response
- Number of receptor remains the same, new ED 50 is now 10 fold higher
Higher ED50 means —- potency
lower
DRC curve: Decrease responsiveness AKA decrease in synthesis of receptor/degradtion of receptor (2)
ED50 + capcity + curve
- ED50 remains the same
- The capacity is lower
DRC curve: Decrease responsiveness AKA decrease in synthesis of receptor/degradtion of receptor and Decrease in affinity/sensitivity (3)
ED50 + curve + capcity
- ED50 greater (right)
- Shift right and move down
- Capacity lower
Change in receptor capacity affects —-, change in receptor affinity affects —–
- maximium responsiveness
- ED50
Hormone receptors fall into two categories:
What + examples
- Intracellular receptors: The receptor molecule is inside the cell (eg steroids and iodthyronines). (Has to enter the cell)
- Plasma membrane receptors: The recognition sites lie att the cell surface (hormones doesnt enter membrane)
Membrane fluidity is determined by
cholesterole
Intracellular receptor (4)
unique + what happens (3 steps)
- Binding domain is inside the cell (cytoplasm or nucleus)
- Usually diffuse through membrane as they are fat soluble and usually bound to carrier protein that increase half life and come off at site of tissue.
- Binds at specific neclear receptor protein and these are ligand-activated transcription factors with each receptor containing hormone binding, DNA binding and activation domains.
- The activated hormone-receptor complex interacts with a specific sequence of DNA referred to as a hormone response element (HRE)
Steroid/ thyroid hormones act through:
Intracellular receptors
Catecholamines, peptide and proteins act through
membrane receptors
There are 2 types of membrane receptors:
+ defierentiate futher into sub categories + ex
Receptor and effector sites are contained in a single molecule
- Effector is an enzyme (Ex: tyrosine kinase; EGF, insulin)
- Effector is an ion channel (eg: ligand gated Na channel)
Receptor and effectors are 2 seperate molecules and need a G protein to couple receptor to effector
- Effector is an enzyme (Adenyl cyclase)
- Effector is an ion channel (K+/Ca2+ channel)
Tyrosine Kinase receptors structure (3):
- A single protein chain with extracellular domain that binds the hormone
- Single transmembrane region of 20-22 amino acids (lots of leucine, helical structure)
- An intraceullular domain that has a tyrosine kinase catalytic domain
Insulin and insulin growth factor-1 RTK structure:
- Consist of 2 subunits
1. An alpha subunit that is extraceulluar and ocntains a ligand binding site
2. A Beta subunit that has extracellular, transmembrane and intracellular domains
How does the receptor tyrosine kinase work? (8)
- Hormone binds to extraceullar domain
- Move laterally to dimerize
- Activation of tyrosine kinase in the intraceullular domain
- Autophosphorylation/transphosporation of the receptor.
- LEads to adaptor protein binding
- Activation of MAP kinase by adaptor protein
- Phosphorylation of transcription factors
- Increase transcription = biological response
Nicotinic acetylcholine receptor
- alpha is the hormone binding domain
- Once bound to acetycholine, opens channel Na+ enters cell creates depolarization
Different types of G-protein
-Gs (stimulation of adenylate cyclase)
- Gi (inhibition of adenylate cyclase)
- Gq/11 (stimulation of PLCB)
Adenylate cyclase
what it does + what its product does + how its activated
- Converst ATP into CAMP
- camp activates camp-dependent protein kinase which phosphorylates certain proteins at serine or threonine residues
- ## Activation is through Gs
The effects of Camp-dependent protein kinases on their substrate proteins are reversed by the action of —— which —–
- Phosphoprotein phosphastases
- remove the phosphate by hydrolysis
Phosphodiesterase (2)
what + inhibited by
- Inactivates CAMP by hydrolzying cyclic ring to 5’AMP
- Inhibited by methylxanthines
Explain the turnover Gq process:
- Gq activates phospholipase CB
- PIP2 made from phosphoinositol gets converted from phos CB into DAG and IP3
- IP3 is hydrophillic and bind to ER membrane to release ca2+
- DAG activates protein kinase C
What are the main cluster of neuron that produce pitutary function?
Supraoptic, paraventricular, preoptic nuclei
Anterior pituitary
derived + how secreted/regulated
- cell come from non-neuronal origin (epithelial cell)
- All secreted cells are made from the AP, regulated by neuronal hormones in hypothalamus but axon does not extend to the AP from hypothalamus. It terminates in the medial eminence. Hormones then enter to the hypothalamic-hypophyseal portal system. They are then released into the pituarty and they target cells in AP and do not travel in the blood. They make AP make hormones to be released.
Posterior pitutary (2)
Derived + how cells are secreted
- derived from the brain
- doesn’t contain any secretatory cells in the lobe, any cell secreted came from hypothalamus which travel down the axon and terminate in neural lobe. Stays there until stimulus comes and release into the blood vessels in the pituary and travel to target.
Intermediate lobe
- region between anterior and posterior pituitary associated with adenohypophysis.
Adenohypophysis
Intermediate + tuberal + anterior lobe
Neurohypophysis
Neural lobe + posterior pitutary
