L5 Endocrine Flashcards
Hypophysiotropic hormones
TRH
CRH
GnRH
GHRH
Somatostatin
Dopamine
Chemical classifications of hormones
Amines
Peptides
Glycoproteins
Steroids
Amine Hormones
all are derivatives of the nonessential AA tyrosine
Thyroid hormones: T4, T3
Adrenal Medulla hormones: epinephrine, norepinephrine, dopamine
Catecholamines
Epinephrine
Norepinephrine
Dopamine
Lipophobic, they do not need a carrier to travel in the blood
Thyroid hormones
Lipophilic, need a protein carrier to travel in the blood
Thyroxine
Triidothronine
Peptide Hormones
Chains of amino acids
Initially synthesized as larger preprohormones in the ribosomes, which then are cleaved onto prohormones by enzymes in the ER
Then the golgi apparatus packages them into vesicles, and they are attached to active hormone
Peptide hormone examples
ADH/vasopressin
Insulin
Preprohormone
prohormone from even larger precursor molecule
synthesized on ribosomes, cleaved to prohormones on ER
Prohormones
long-chained precursor that is cut and spliced to make the active hormone
occurs in golgi apparatus
Example of synthesis of peptide hormone
- Preproinsulin: a, b chains and connecting peptide are made on ribosomes
- Proinsulin: Preproinsulin is cleaved to proinsulin in ER
- Insulin: Proinsulin is cleaved to insulin in golgi apparatus
- Secretory vesicles contain and release insulin and C-peptide
Glycoprotein hormones
Long polypeptides bound to one or more carbohydrate groups
examples are FSH and LH
Steroid Hormones
all synthesized from cholesterol
they are lipophilic, meaning they need a protein carrier to travel in the blood
Adrenal cortex, Gonads, and Placenta hormones are examples
Corticosterioids
Aldosterone
Cortisol
Dehydroepiandrosterone and androstenedione
Aldosterone
mineralcorticoid
Na+ reabsorption in exhange for K+ or H+ secretion by kidneys
part of the renin-angiotensis-aldosterone system
low blood pressure is a trigger
resides in zona glomerulosa
Cortisol
glucocorticoid
helps with metabolism, response to stress, immune modulation
resides in zona fasiculata/reticularis
DHEA
similar effects to testosterone, much less potent
resides in zona fasiculata/reticularis
Synergistic hormonal interaction
> 2 hormones work together to produce a result
can be additive or complementary
Additive Synergistic hormonal interaction
each hormone separately produces a response, but together they produce a greater effect
ex: NE and E on the heart
Complementary Synergistic hormonal interaction
each hormone stimulates a different step in the process
ex: FSH and testosterone on sperm production
Permissive hormonal interaction
1 hormone enhances the effectiveness of a 2nd hormone to produce a specific result
ex: thyroid hormone and epinephrine on rate of lipolysis
Antagonistic
2 hormones produce opposite effects
ex: insulin and glucagon
Hormone plasma concentration
Plasma concentration reflects the rate of secretion. Most do not accumulate in the blood because they have short half lives.
Hormone effects and concentration
Effects are very dependent on concentration
physiological concentrations produce normal tissue responses
Deficit/excess of hormone produces pathological responses
Hormone release
SECRETION
usually released in short bursts, plasma concentration can change rapidly over brief time
most have a 24 hour cylical behavior due to variations in neural paths
cortisol is low late at night and high in the morning
Hormone receptors
ability of any target tissue to respond to a hormone depends on the presence of specific receptors on the cell surface or inside the cell
a hormone can influence its target cells’ ability to respond by regulating the receptors
Up-regulation
increase in number of receptors
usually results from prolonged exposure to low hormone concentrations
Down-regulation
decrease # of receptors
usually results from exposure to high concentration of hormone
Properties of receptors
Specificity
High Affinity/bond strength
Low Capacity/saturation
Lipophilic hormones
cortisol/steroids, thyroid hormones
receptors are inside the cytoplasm or nucleus, need a protein carrier
Lipophobic hormones
receptors are on the cell membrane
Mechanism of action for lipophilic hormones
- Hormones bind to specific carrier proteins in plasma
2 Hormone dissociates from carrier protein to pass through lipid bilayer of target cell membrane - Hormone binds to a receptor that is inside of the cell
- Steroid-receptor complex translocates to nucleus
- DNA-binding domain of receptor binds to DNA inside cell
- Dimerization occurs, stimulates gene transcription
- Hormone binding results in activation of particular genes resulting in changes in protein synthesis
- Activation of receptor results in delayed responses
Hormones and 2nd messenger systems
peptides, glycoproteins, catecholamines bind to receptors in the cell membrane
extracellular hormones are transduced into intracellular 2nd messengers
can impact ion channels, enzyme activity, G-proteins
What is important for PTs with 2nd messenger systems?
- Many drugs bind to signaling cascades
- One hormone can have different effects depending on receptor subtype it binds to
- Drugs can have the same effects as NT or hormones by impacting the downstream of the 2nd messenger system (backdoor activation)
- If a drug acts on multiple 2nd messenger systems, it will have a broad unanticipated impact
Main classes of 2nd messenger systems
Adenylate cyclase
Phsopholipase C
Tyrosine Kinase
Adenylate Cyclase-cAMP
most common, enzyme system that always requires a G protein
- hormone binds to G protein
- beta-2 subunit dissociates and activates AC
- cAMP activates protein kinases (adds a phosphate)
- cAMP is inactivated by phosphodiesterase (PDE)
Caffeine and cAMP
caffeine inhibits the action of cAMP PDE, which ultimately prevents the breakdown and inactivation of cAMP
cAMP concentration inside cells stays higher for longer
Phospholipase C
- Binding of epinephrine to alpha 1-adrenergic receptor activates G-protein that is coupled to PLC
- PLC splits phospholipid into IP3 and DAG (2nd messengers)
- IP3 opens CA2 channels in ER
- Influx of Ca2, Ca2 binds to calmodulin
- Calmodulin activates specific protein kinases that modify enzymes
Epinephrine and 2nd messenger systems
Can act through two second messenger systems
Allows for a graded response
stimulate alpha 1 and higher levels
stimulates beta 2 cells, at low levels
alpha 1 cells
coupled to PLC, IP, Ca
most vascular smooth muscle
pupillary dilator muscle
liver (increases glycogenolysis)
Alpha 2 cells
activation leads to decreased AC/cAMP
inhibits NT release
Beta 1 cells
activation leads to increase AC/cAMP
increase HR and contractility
Beta 2 cells
activation leads to increase AC/cAMP
vascular smooth muscle vasodilation
bronchodilation
gluconeogenesis, glycogenolysis
Beta 3 cells
activation leads to increase AC/cAMP
lipolysis
Tyrosine Kinase
no G protein
main system for insulin
have receptor proteins in plasma membrane, that add phosphate groups to residue tryosine
1.Receptor has 2 units that come together (dimerization), activating enzymatic portion of tyrosine kinase
2. Receptor autophosphorylates, increasing own activity
3. Receptor phosphorylates other signaling molecules
Hormones are metabolized by
- Target cell
- Peptide hormones bound to receptors are removed by endocytosis
- Depends on secretion and rate of removal
Inputs that act directly on endocrine cells
ions or nutrients
neurotransmitters
hormones
Ions or nutrients and hormone secretion
- Some hormones are directly controlled by plasma concentration of specific ions and nutrients
- These hormones will regulate w/negative feedback, the concentration of the nutrient/ion
Neurons and hormone secretion
- hormones of the hypothalamus and post pituitary are controlled by the CNS
- Adrenal medulla is stimulate by sympathetic preganglionic fibers
Other hormones and hormone secretion
- hormone secretion is controlled by negative feedback
- Ant. pituitary and hypothalamic secretions are controlled by the target organs they regulate
- Feedback loops maintain normal hormone concentrations
hormones can provide negative feedback for other hormones
Posterior Pituitary gland
outgrowth of the hypothalamus
neural and vasculature connections
ADH/Oxytocin hormones are produced in the hypothalamus and then are released in vasculature in the posterior pituitary or they are stored here
secreted hormones go to a capillary bed that leads to the main bloodstream
Anterior Pituitary
no neural connections to the hypothalamus
blood from the median eminence (hypothalamus) flow into the anterior pituitary
hormones from the hypothalamus cause the production of new hormones from the anterior pituiatry, which are released into the blood
hormones are released into MAIN BLOODSTREAM
Hormones of the anterior pituitary
FSH, LH = gonads
Growth Hormone = Liver, tissues, organs
TSH = thyroid
Prolactin = breasts
ACTH = adrenal cortex
Trophic effects and anterior pituitary
hormones from the AP have trophic effects on target gland
health of target glands depends upon stimulation by anterior pituitary for growth
Hypophysiotropic hormones
=made in the hypothalamus and control secretion of AP hormones
=called either releasing or inhibiting hormones
=transported down axons which terminate in the median eminence
=usually a part of a 3 hormone sequence
Growth hormone releasing hormone
stimulates GH
which stimulates liver to secrete IGF or metabolism
Thyroid releasing hormone
stimulates thyroid stimulating hormone
stimulates T3 and T4
Somatostatin
inhibits GH secretion
Corticotropin releasing hormone
stimulates ACTH release
stimulates cortisol release
The hypothalamus receives…
Inhibitory and stimulatory input from ALL areas of the CNS
