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Endo - Exam 1
Comprised of material through Exam 1 2014
167
Physiology
Graduate
02/01/2014

Additional Physiology Flashcards

 


 

Cards

Term
Endocrinology
Definition
  • Subdiscipline of physiology
  • Study of Hormones:
  • `````Physiological roles
  • `````Cellular sources
  • `````Biosynthesis
  • `````Chemistry and storage
  • `````Factors and mechanisms controlling secretion
  • `````Cellular Mechanisms of hormone action
  • `````Pathophysiology of endocrine sys. disfunction
Term
Comparative Endocrinology
Definition
Study of the endocrine system of non-human vertebrates and occasionally invertebrates
Term
Ancient/Primitive/Barbaric form of hormone replacement therapy
Definition
Belief in eating the organs of certain animals, and even enemies in battle would imbue or transfer said animal or enemy's strength, power, courage, etc.
Term
Hippocrates' era
Definition
450-350 BC
Term
Hippocrates Humoral Hypothesis
Definition

One's physical and mental health depended on the balance of the four humors.

 

This theory lasted until at least the 18th century.

Term
Four Humors
Definition
  1. Blood
  2. Phlegm
  3. Black Bile
  4. Yellow Bile
Term
Aristotle's era
Definition
~350BC
Term
Aristotle's contribution to endocrinology
Definition
He described the effects of castration on various animals, including chickens
Term
Greeks knew the importance of this organ for sexual characteristics and reproductive function, even if the mechanism was not known.
Definition
Testis
Term
Earliest inquiries into endocrinology were related to testis and reproduction because:
Definition
  • External structure
  • Easy accessability
  • Interest in human sexuality
Term
Castration purposes in ancient societies
Definition
  • Eunuchs as guards for harems or brothels
  • Castrados in church choirs
  • Form of punishment and humiliation (Still even today, in some societies)
  • Animal castration to improve the palatability of meat
Term
William Harvey's big year and location
Definition
1628, Frankfurt
Term
William Harvey's contribution to Endo
Definition

He first wrote "On the Motion of the Heart and Blood in Animals"

 a.k.a. De Motu Cordis

 

It named the blood as the circulation medium throughout the body, pumped by the heart, in a circuit.

Term
John Hunter's big year
Definition
1771
Term
John Hunter's big contribution
Definition
  • Successfully transplanted gonads among birds:
  • Demonstrating the testes droves maleness and the ovaries drove femaleness.
  • Still no awareness of mechanism of secretion into blood at the time.
Term
Bordeau's big year
Definition
1775
Term
Bordeau's contribution
Definition
  • The first to report and describe what is now called "internal secretion and humoral integration"
  • His Hypothesis: Each gland and organ of the body is a workshop producing secrections, which pass into the blood and influence total body functions
Term
Berthold's big year and location
Definition
1849, Germany
Term
Berthold's contributions
Definition
  • Conducted the first formal study in endocrinology
  • Roosters - Capons : First recorded ablation / replacement experiment on testes.
Term
What are some characteristics of the asymmetry of testicles, a common feature in avian and mammalian species?
Definition
  • Left usually bigger than right
  • Age-related, larger left testicle found in younger birds
  • More primordial germ cells in left, aquired from right
  • Age-related, larger right found in older roosters
  • (Similar asymmetry found in ovaries in females)
Term
Why is there asymmetry of testicles?
Definition
  • Developmental cost of having two large testicles
  • `````Metabolic cost of two equally large testicles is too great because of the potent immunosuppressive effect of testosterone.
  • `````Greater mass could affect flight
  • Right Testis may be primarily compensatory (back-up)
  • `````Low degrees of asymmetry suggests right testis has become fully developed to compensate for inadequate left testis
  • `````Males in poor health might have larger right testis than left
Term
Most important experimental animal model in the history of endocrinology
Definition
The chicken
Term
Bruce Glick and Timothy Chang
Definition
(Relatively) unknown grandfathers of humoral physiology. Their research laid the groundwork for the development of immunology
Term
Claud Bernard's big year
Definition
1865
Term
Claude Bernard's contribution
Definition
  • Firmly established, through chemical analysis, the idea that blood is altered when it passes through an organ.
  • In his research, the liver was the primary organ studied.
  • FIRST TO USE THE TERM "INTERNAL SECRETION"!!!!
Term
Brown-Sequard's big year
Definition
1875
Term
Brown-Sequard's contribution
Definition
  • first use of tissue extracts in a clinical setting
  • injected dog-testes-extracts into himself, claimed rejuvenation
  • public interest drove further research
Term
Gull's year and contribution
Definition
1874 - Associated clinical signs to thyroid disorders
Term
Murray's big year and contribution
Definition
  • 1891 - treated hypothyroidism with thyroid extract
  • FIRST CLINICAL TREATMENT FOR AN ENDOCRINE DISORDER, EVEN THOUGH THYROID HORMONES HADN'T YET BEEN ELUCIDATED
Term
Von Mering and Menkowski's year and contribution
Definition
  • 1889 - DIABETES MELLITUS term coined.
  • Ablation replacement experiments on dogs/pancreas
  • Did not know about insulin yet
Term
Bayliss and Starling's year and contribution
Definition
  • 1902-1905
  • Conducted experiments leading to discovery of SECRETIN - THE FIRST DISCOVERED HORMONE!!
  • It's considered the "Start of endocrinology"
  • S- Coined the term "HORMONE" !!
Term
Takamine's big year and contribution
Definition
1902 - Purified the first hormone - epinephrine
Term
Stolz and Dakin's big year and contribution
Definition
1904 - first to synthesize a hormone - epinephrine
Term
Banting and Best big year and contribution
Definition
1921 -  INSULIN (first-discovered protein hormone)!
Term
What techniques developed in the 1940s and 1950s?
Definition
  • Electron Microscopy
  • Radioactive Isotopes
  • Tissue Culture
  • Analytical Methods
Term
What progress was made in the 1950s-1960s?
Definition
  • Separation techniques
  • Purification techniques
  • Synthesis of protein hormones
  • Studies on mechanism of hormone actions - PATHWAYS!!
Term
Du Vigneaud's big year and contribution
Definition
  • 1953 
  • Determined structure of, and synthesized the first peptide hormones oxytocin and vasopressin/ADH/AVP
  • (which are found in the posterior pituitary)
Term
Sanger's big year and contribution
Definition
  • 1954
  • Determined the chemical structure of insulin
  • First to determine the structure/sequence of any protein hormone
Term
Pig Insulin structure characteristics
Definition
  • 51 Amino Acid residues per molecule
  • 2 chains (A&B)
  • 1 intrachain disulfide bridge
  • 2 interchain disulfide bridges
Term
Cleaver and Carlson's big year and contribution
Definition
  • 1960
  • Discovered ecdysone, insect molting hormone that induces cell nucleus RNA increase (chromosome puffing)
  • Showed that hormones could affect DNA / RNA
Term
Katsoyannis's big year and contribution
Definition
  • 1963
  • Synthesized insulin 
  • The first protein hormone to be synthesized
Term
Earl Sutherland's big yearS and contribution
Definition
  • 1957-1960
  • Discovered cAMP as a hormone mediator
  • Elucidated the mechanism of action of some hormones
  • Discovered epinephrine affects liver to induce increase in blood glucose
  • 1971 - NOBEL PRIZE!
  • "Showed that hormones do not have a direct, but rather an indirect action via intermediates, which regulate, but do not mediate reactions"
Term
Guilleman and Schally's big year and contribution
Definition
  • 1950s-1960s
  • Elucidated hypothalmic control of the pituitary endocrines
  • Discovered releasing factors
  • 1st of all was Corticotropin Releasing Factor (CRF)
  • Considered the "Fathers of neuroendocrinology"

1977 - Shared NOBEL PRIZE with Berson and Yalow

 

 

Term
Berson and Yalow's big year and contribution
Definition
  • 1960
  • Developed radioimmunoassay (RIA) techniques
  • Allowed for accurate measurements of hormone concentration (picogram/mL);
  • Again, insulin was the first measured

1977 - Shared NOBEL PRIZE with Guilleman and Schally

Term
Claude Bernard's year and contribution
Definition
  • 1849
  • Originated the concept of internal vs external environment
  • "milieu interior which is the condition of free and independent life"
Term
Walter B. Cannon's year and contribution
Definition
  • 1932
  • Built upon Claude Bernard's concept of milieu interior
  • coined the term homeostasis and expanded idea
  • steady state condition
  • homeostasis is the result of a organized self-regulation
  • early idea of fight or flight response
Term
Homeostasis definition
Definition
  • Process by which organisms maintain the "constancy" of their internal environment in response to changes in their external environment
  • Self adjusting mechanism involving feedback regulation (negative more commonly, and positive)
  • Works to maintain the internal environment within a narrow range of conditions conducive to life
Term
Major aspects of internal environment in need of balance and control in order to survive:
Definition
  • Glucose (30-300mg/dL)
  • Calcium
  • Sodium
  • Body Temp
  • Blood Volume/Body Fluid levels
Term
What's the most prominent example of multilevel control of the endocrine system?
Definition
  • The "Hypothalamus-pituitary-endocrine organ axis"
 
  • The Hypothalamus -> Pituitary -> Endocrine Gland     -> Target Organ -> DESIRED EFFECT
Term
What are the four characteristics of "Negative Feeback"?
Definition
  1. The response of the target organs/glands diminishes the original stimulus
  2. Output of a pathway inhibits inputs to the pathway
  3. Can continue forever
  4. Maintains homeostasis
Term
General chain of events in "Negative Feedback"
Definition
  1. Destabilizing stimulus is sensed
  2. Hormone secretion is triggered
  3. Hormone activity lowers a parameter to bring process back to pre-stimulus state
Term
Functions requiring Calcium (Ca2+)
Definition
  • Secretion
  • Blood clotting
  • Muscle contraction
  • Thermoregulation
  • Nerve signal conduction

Its concentration is maintained within very narrow limits both inside and outside the cell

 

Its level in the blood is what is regulated by the body

Term
Calcium Homeostasis
Definition
[image]
Term
Simplified Regulation of Blood Glucose Levels
Definition
  1. Elevation of blood glucose concentration
  2. Beta cells in pancreas release insulin
  3. Insulin facilitates entry of glucose into cells
  4. Blood glucose level falls sufficiently
  5. The stimulation for insulin release falls
  6. Insulin secretion stops
Term
What's an example of a "feed forward mechanism"?
Definition
GI hormones trigger insulin secretion before BGL increases
Term
General Overview of Endocrine Regulation
Definition
[image]
Term
Positive Feedback overview
Definition
[image]
Term
Positive Feedback Characteristics
Definition
  1. Unstable system
  2. It is used to trigger a sudden even / phenomenon
  3. Cannot continue forever / always has a limit
  4. Does not result in homeostasis
  5. Beneficial in only special circumstances
  6. Usually terminated by a dramatic event (i.e. Childbirth, Death)
Term
Ovulation - Positive Feedback Example
Definition
[image]
Term
LH Surge and Ovulation
Definition
[image]
Term
Neuroendocrine Cell definition
Definition
a cell that gets a NERVOUS input, and releases a HORMONE into the BLOOD
Term

Neuroendocrine Integration

definition and examples

Definition

Def: an intertwining of the nervous system and the endocrine system

 

Ex: Adrenal medulla - releases epinephrine, norepinephrine, and dopamine into the blood.

(It's innervated by the sympathetic autonomic nervous system)

Term
Hormone Storage
Definition
Many hormones are kept in vesicles, analagous to neurotransmitters kept in vesicles ready to be released
Term
Homonal Effects
Definition
These can last up to 10x as long as neurotransmitters
Term
What is the major center of neuroendocrine integration?
Definition
Hypothalamus and Pituitary Gland
Term
Where do Hypothalamic neurosecretory cells release factors?
Definition

The hypothalamic median eminence,

and the bloodstream. 

Term
What is a hormone?
Definition
This is a chemical messenger that coordinates the activities of different cells in a multicellular organism, and is a chemical substance that is synthesized by particular endocrine glands, and then enters the bloodstream to be carried to a target tissue, which has specific receptors that bind to it.
Term
What are the different types of Chemical Integration via Delivery (what are the different types of delivery)?
Definition
  1. Endocrine/Neuroendocrine
  2. Paracrine 
  3. Autocrine
  4. Neurocrine
  5. Intracrine
Term
Endocrine/Neuroendocrine Delivery definition
Definition
Delivery via the bloodstream to the target tissue or cells
Term
Paracrine Delivery definition
Definition
Delivery via diffusion to neighboring cells
Term
Autocrine Delivery
Definition

Delivery via hormone feedback on the cell of origin in a form of self regulation

 

(e.g. the ultrashort loop)

Term
Neurocrine Delivery definition
Definition

Delivery via hormones released into the synaptic cleft by neurons that are in contact with the target cells

 

(e.g. peptide hormones)

Term
Intracrine Delivery definition
Definition

Delivery via hormonal action within a cell

 

(e.g. steroid hormones acting through intracellular (mostly nuclear) receptors).

Term
Mechanisms of Hormone Delivery (Cont.)
Definition
[image]
Term
How Hormones Function
Definition
[image]
Term
Hormone Inactivation, why? how? what?
Definition
  1. They must be metabolized rapidly and removed, so FEEDBACK MECHANISMS can operate and cellular functions can be regulated
  2. Removal/inactivation of these follows a pattern of exponential decay (kinetics).
  3. Its "half-life" is how its longevity is measured
  4. Synthetic versions/analogues are designed to have a longer half-life in order to be more effective for longer periods of time than those naturally occuring
Term
What are the 4 different ways to degrade a peptide hormone?
Definition
  1. Peptidases - e.g. cathepsins (proteases): in lysosomes split all the peptide bonds in the molecules
  2. Exopeptidases - degrade peptides from the carboxy-terminal OR the amino terminal end.
  3. Endopeptidases - e.g. trypsin and chymotrypsin: degrade proteins at specific sites like lysine or arginine, and phenylalanine or tryptophan or tyrosine
  4. Deamination or reduction of disulfide bonds (like the ones in insulin) - This occurs in the kidney, liver, and in target cell lysosomes
Term

How can a hormone increase its half-life?

 

Definition

1. Be a steroid hormone (which can hang out in adipose tissue due to the steroids' lipophilicity)

2. Bind to a protein carrier

3. Stay away from the liver and kidney to avoid the 2-phase degradation process

Term
How do hormones get degraded?
Definition
Enzymes add functional groups (e.g. hydroxyl groups) to the broken up hormones, and that makes them conjugate to sulphates or glucuronic acid. Makes them more water soluble. Excreted by the kidney, or by the liver as bile salts.
Term
Structure of Steroid Sulfates and Steroid Glucuronides
Definition
[image]
Term
How do hormones interact with each other?
Definition
  1. Concerted/Additive - Thyroid,  T3, Growth Hormone works on RNA expression and thus, growth
  2. Non-Additive - Epinephrine works on insulin and glucagon, so does cortisol to release more glucose into the bloodstream
  3. Synergistic - Tand Cortisol, genes affected, somatotropin
  4. Permissive - estradiol permits expression of progesterone receptors in oviduct
Term
Concerted/Additive definition
Definition
The two hormones cause the same response and the combined effect of the hormones is simply the sum of the separate actions of the individual hormones (hormones act via different mechanisms)
Term
Non-Additive definition
Definition
two different hormones cause the SAME EFFECT, but the hormones MAY NOT ACT BY THE SAME COMMON MECHANISM
Term
Synergistic definition:
Definition
The effect of the two different hormones is more than the sum of the separate effects of the individual hormones
Term
Permissive definition
Definition
If two different hormones have NO EFFECT ON THEIR OWN, but must be present for ANOTHER HORMONE TO HAVE AN EFFECT. (could act by increasing the number of receptors, or affecting the activity of the second messenger system for the other hormone)
Term
Physiological effects of hormones depend on what?
Definition
  1. Concentration of hormone in blood and exracellular fluid
     
  2. Hormone-receptor interaction (Binding)
     
  3. Intracellular signaling mechanisms (Phosphorylation, signal transduction pathway, etc.)
     
Term
What are some hormones that ebb and flow on a daily basis?
Definition
  • Melatonin
  • Cortisol
  • Thyrotropin
  • Growth hormone
Term
What are some body metrics that ebb and flow on a daily basis?
Definition
  • Core Body Temperature
  • Urine Volume
  • Cerebral Blood Flow
  • Systolic Blood Pressure
Term
Why do hormones get secreted in "Pulses" with a certain "Rhythm"?
Definition

It's a consequence of 

1. Feeback Controls

2. Regulated Secretion

3. Limited lifespan of a hormone

Term
What are the 7 patterns of Hormone Secretion? -what are their lengths? (what's and example)?
Definition
  1. Circhoral - an hour (testosterone)
  2. Ultradian - recurrent periods/cycles repeated during a 24-hour circadian day (sleep, feeding)
  3. Circadian - endogenously driven cycle of roughtly 24-hours (Melatonin, corticosteroids)
  4. Quotidian (diurnal) - occurs every day (body temperature)
  5. Infradian - periods longer than a day (human menstrual cycle)
  6. Circatrigintan - a month, approximately (ovulation)
  7. Circannual (seasonal) - a year (thyroxine, dog reproduction)
Term
The most important driver of biological rhythms
Definition
light
Term
How are Biological rhythms expressed?
Definition
They are expressed as Cycles (oscillations), which can change over time.
Term
All seven different types of rhythms have these two things in common
Definition
They all have PERIODICITY (time interval between two similar points in an oscillation) and PHASE (any point in their cycle)
Term
External or environmental factors involved in the maintenance of Biological/Endocrinological Rhythms
Definition

Diet

Disease

Light

Temperature

Noise

Term
Internal Factors in maintenance of biological/endocrinological rhythms
Definition

Ca++

Lipid

Temperature

Na+

P

Mg

Term
Effects due to hormones
Definition
  1. Changes in cellular metabolism 
  2. Activate genes to influence gene expression and ultimately protein synthesis
  3. Alter catalytic rates of enzymes by phosphorylation or dephosphorylation
  4. Alter membrane permeability (affects transport processes and ion movements, muscle contraction, exocrine secretion, and water permeability)
Term
Effects due to hormone actions
Definition
  1. Morphological changes (sex steroids alter appearance)
  2. Act as mitogens (accelerate cell division or alter gene expression to trigger differentiation of cells)
  3. Simulate overall rate of protein synthesis or synthesis of specific proteins
  4. Stimulating smooth muscle contractions (oxytocin stimulates contraction of myoepithelium in the mammary gland for milk ejection)
Term
Effects are due to hormones
Definition
  1. Affects exocrine secretions; (secretin peptide hormone from intestine stimulates pancreatic secretions)
  2. Controls endocrine secretions (trophic hormones from ant.pit. stimulate/inibit hormone secretion from target organs)
  3. Regulate ion movements across membranes and permeability to water (ADH, vasopressin)
  4. Affects behavior (sex-related behavioral characteristics, maternal behavior)
Term
Hormone Selectivity
Definition
  1. Target cells have specific receptors 
    • (hypophyseal - portal system)
      • hypothalamus to the pituitary gland
      • smaller quantities of hormones are needed due to less dilution across space.
  2. Many Hormones linked to CARRIER PROTEINS
    • stabilize the hormone / increase half-life
    • (Sex hormone-binding globulin)
Term

Hormone Selectivity

(Receptor specificity)

Definition
  1. Specific (protein) receptors bind a specific hormone
  2. Receptors present in small numbers (10,000 molecules per cell)
  3. Two types (cell-surface and intracellular)
  4. Peptide / protein hormones usually do not enter the cell, but interact with cell-surface receptors
Term
Hormone Action / Activity
Definition
  1. Activity mediated by how many receptors are bound to hormones
  2. Cell-surface receptors (usually) require a second-messenger system to transmit the hormone response signal from the outside to inside
    • Protein kinase A phosphorylation
  3. Steroid hormones / Thyroid hormones enter the cell to interact with intracellular receptors to regulate gene expression (penetrate plasma membrane)
Term
Cell-Surface Receptor pathway example
Definition
  1. -Hormone 
  2. > membrane spanning receptor 
  3. > Active protein Kinase 
  4. > Protein Substrate phosphorylation 
  5. > Cellular response
Term
Hormone receptor locations
Definition
  1. Cell surface
  2. Inside the cell
Term
Receptor Types
Definition
  1. Extracellular
    1. Second messenger system
      • cAMP 
      • cGMP
  2. Intracellular Receptors
    • Protein Kinase A (PKA)
    • Protein Kinase C (PKC)
Term
Extra cellular receptor properties
Definition
  1. Large macromolecules
    • Insulin receptor= 200-400kDa (2alpha 130kDA/2beta subunits 90kDa)
    • Must span the membrane, bind a hormone, and undergo conformational change- requires many moving subunits.
Term
Second Messenger Systems
Definition
  1. Adenylate cyclase
    • cAMP or cGMP
    • PKA or PKC
  2. Inositol Phosphate
    • Phospholipase C
    • Calcium dependent
Term

cAMP messenger system example:

Epinephrine

Definition
  1. Epinephrine binds to RECEPTOR, causes conformational change
  2. Activates G-PROTEIN (alpha, beta&gamma subunits dissociate)
  3. The active G-protein (now with GTP bound rather than GDP) binds to ADENYLATE CYCLASE
  4. Alter activitiy of a.c. converts ATP to cAMP!
  5. cAMP activates PROTEIN KINASE A!
  6. PKA phosphorylates various targets, activating or deactivating them, to initiate a cellular response 
    • (In epinephrine's case, elevates blood glucose levels by:
      • phosphorylating "phosphorylase kinase" which then 
      • phosphoylates "Glycogen phosphorylase A" which then 
      • Degrades Glycogen to 
      • Release glucose into the bloodstream)
Term
The "other" cell-surface receptor system (not Adenylate Cyclase->cAMP->PKA)
Definition
  1. Hormone binds to the receptor (transcription factor)
  2. Activates PHOSPHOLIPASE C which splits into
    • Inositol phosphate (in the cell membrane) and 
    •  Diacylglycerol
  1. Inositol Phosphate increases levels of intracellular calcium
  2. DAG activates Protein Kinase C (along with the C++)
Term
A typical way to deactivate a hormone's effect on target intracellular proteins
Definition
Remove a phosphate using phosphoprotein phosphatase
Term
This is an amplification step in the Adenylate cyclase pathway
Definition
the formation of cAMP
Term

1.What enzyme degrades cAMP?

 

2. What's the end product of the degradation?

Definition

1. Phosphodiesterase

 

2. AMP

Term
What are 4 reasons cAMP is a good second messenger molecule?
Definition
  1. Chemical stability - derived from ATP
  2. ATP is ubiquitous - is formed from ATP in a single reaction (doesn't take a lot of energy to make)
  3. It's an allosteric regulator ( not a metabolic precursor) - controlled separately independently of metabolism
  4. It's a small and easily diffusable molecule, has functional groups that allow specific binding to regulatory subunits of protein kinases (PKA)
Term
Adenylate Cyclase can be activated or inhibited by what proteins?
Definition
G-Proteins
Term
What are some physiological or cellular responses that are mediated by cAMP?
Definition
  • Increased heart rate
  • Cortisol secretion
  • Glycogen breakdown
  • Fat breakdown 
Term
What molecules activate cAMP pathway?
Definition
  1. Cholera toxin - increases levels of cAMP
  2. Forskolin- a diterpine natural product that activates adenylate cyclase
  3. Caffeine and theophylline- inhibits cAMP phosphodiesterase
  4. Bucladesine (dibutyryl cAMP, db cAMP) - Also an inhibitor of phosphodiesterase
Term
What molecules inhibit cAMP pathways?
Definition
  1. cAMP phosphodiesterase- and dephosphorylates cAMP into AMP,
  2. Gi Proteins- inhibitory G proteins inhibit adenylate cyclase,
  3. Pertussis toxin- decreases cAMP levels (whooping cough)
Term
What enzymes degrade cAMP?
Definition

PHOSPHODIESTERASES!!!

(PDE)

  1. PDE1A and PDE1B preferentially hydrolyse cGMP
  2. PDE1EC degrades both cAMP and cGMP, high affinity
    • (Generic PDE1 does more than 50 percent of hydrolysis of cyclic nucleotides in airway smooth muscle)
Term

What does Phosphodiesterase do?

(picture)

Definition
[image]
Term
Facts about PKA
Definition
  1. aka cAMP-dependent protein kinase
  2. activity depends on cAMP levels w/in the cell
  3. regulates (indirectly) metabolism of glycogen, sugar, and lipids
  4. activity is affected by epinephrine and glucagon (upregulated via adenylate cyclase)
  5. phosphorylates many important metabolic enzymes
    • acetyl-CoA carboxylase
    • pyruvate dehydrogenase
      • allosteric regulation inhibits lipogenesis
      • promotes net gluconeogenesis
      • (insulin works in opposition and promotes lipogenesis)
Term

Calcium-Dependent phospholipase C-protein kinase

(PKC)

Definition
  • Primary intracellular effector in this pathway is Ca2+
  • Activates calcium-dependent protein kinase C
Term

Phospholipase C-PKC System

(steps)

Definition
  1. Hormone binds to receptor, 
  2. G-Protein activated
  3. Phospholipase C activation
  4. Phosphatidylinositol-4,5-bisphosphate hydrolyzed to produce:
    • Diacylglycerol (DAG) -> ER Ca2+ Channels open
    • Inositol-1,4,5-phosphate (IP3) -> activates PKC (w/Ca2+)
  5. PKC then phosphorylates cellular proteins to regulate their activity
Term
How is G Protein activity studied?
Definition
  1. Using 
    • a non-hydrolysable form of GTP
    • Cholera toxin
    • (both inhibit GTPase activity)
Term
What does the RAS oncogene do?
Definition

Codes for a permanently active G-Protein

(might explain its role in the development of cancer)

Term
What is the "Yin-Yang Hypothesis"?
Definition

The cGMP system works in opposition to cAMP

 

(activation of cAMP-dependent kinases results in smooth muscle relaxation, while activation of cGMP-dependent kinases results in smooth muscle contraction)

Term
cGMP is more potent than cAMP
Definition
levels of cGMP is normally 10-50 times lower than those of cAMP, creates the same effect in the body
Term

What hormones act via

the adenylate cyclase-cAMP-protein kinase A

pathway?

Definition
  1. Glucagon
  2. Vasopressin
  3. Thyrotropin (TSH)
  4. Adrenocorticotropic hormone (ACTH)
  5. Luteinizing hormone (LH)
  6. Follicle stimulating hormone (FSH)
  7. Chorionic gonadotropin
  8. Parathyroid hormone
  9. Thyrotopin
  10. Thyrotropin Releasing Hormone (TRH)
  11. Secretin
  12. LH Releasing Hormone (LHRH)
  13. Calcitonin
Term
Intracellular Receptors are found where?
Definition
Cytoplasm and Nucleus
Term
What receptors are found in the nucleus?
Definition
  1. Thyroid hormone receptors (TR)
  2. Estrogen receptors (ER)
  3. Progesterone receptors (PR)
  4. Retinoic Acid receptors (RAR)
  5. 1,25-dihydroxy vitamin D3 receptors (VDR)
Term
What hormones are found in the cytoplasm?
Definition
  1. Glucocorticoid receptors (GR)
  2. Mineralocorticoid receptors (MR)
  3. Androgen receptors (AR)
Term
What do receptors for steroid hormones act as, to regulate the transcription of target genes
Definition
TRANSCRIPTION FACTORS!
Term
Steroid receptors of the nuclear receptor family are all...
Definition
transcription factors (Type I receptors)
Term
Upon binding by the hormone
Definition
  1. the receptor undergoes a conformational change
  2. the hsp90 comes off
  3. the receptor and hormone (bound together) enter the nucleus to act upon transcription
Term
Types of Steroid Receptors
Definition
  1. Group A: Estrogen Receptors (sex-hormones)
  2. Group B: Estrogen-Related Receptor
  3. Group C: 3-Ketosteroid Receptors
Term

What are the 4 common steroid hormone receptor domains?

 

What do they do?

Definition
  1. Variable Domain - 
    • N-terminal and is the most variable domains
  2. DNA Binding domain - 
    • Centrally located highly conserved DNA binding domain;
    • This region controls which gene will be actived.
    • On DNA it interacts with the hormone response element (HRE)
  3. Hinge Region - 
    • Controls the movement of the receptor to the nucleus
  4. Hormone binding domain - 
    • Moderately conserved ligand binding domain
Term
Classes of nuclear receptors:
Definition
  1. Type I
    • Bind Steroids
    • Have a heat shock protein (hsp) associated with the inactive receptor that will be released when the receptor interacts with the ligand
  2. Type II
    • HAVE NO HEAT SHOCK PROTEIN (NO HSP)
    • Located only in the cell nucleus
Term
Type I nuclear receptors all bind to...
Definition
Steroid hormones
Term
The cell membrane aldosterone receptor has shown what:
Definition
to increase the activity of the basolateral Na/K ATPase
Term
Mechanism of action: Steroid Hormones
Definition
  1. Hormone penetrates plasma membrane
  2. Receptor/hsp90 complex binds hormone in cytosol
  3. Hormone/receptor/hsp90 complex alltogether enters nucleus, 
  4. Hsp90 chaperone dissociates
  5. Receptor hormone complex binds to DNA Associated receptor
  6. Phosphorylation of sites on chromatin
Term
Mechanism of action: Type II
Definition

NO HSP

Hormone binds to receptor (Transcription factor) in the nucleus

Transcription factor affects transcription of RNA

 

Term
What are the different methods for termination of hormone action
Definition
  1. once the hormones interact with their receptors, the cluster together and trigger vesicularization of the membrane and endocytosis
  2. receptors are then degraded by lysosomal enzymes or the receptor can be recycled
  3. The hormone at the cell surface can be degraded by plasma enzymes
  4. The cyclic nucleotides are degraded by phosphodiesterases and the phosphorylated proteins are dephosphorylated by phosphoprotein phosphorylase
Term
What are the 4 different types of hormones?
Definition
  1. Steroids - (cholesterol as a building block)
  2. Proteins, polypeptides, and glycoproteins (added sugar moiety)
  3. Amino-acid derivatives (especially derivatives of tyrosine; neurotransmitters)
  4. Fatty acids and derivatives (prostaglandins)
Term
What are the 11 endocrine "glands"
Definition
  1. Pineal gland
  2. Thyroid gland
  3. Heart
  4. Bone
  5. Pituitary gland
  6. Parathyroid gland
  7. Pancreas
  8. Adrenal gland
  9. Kidney
  10. Ovaries
  11. Testes
Term
What's a regularly mentioned avian endocrine gland?
Definition
Bursa Fabricious
Term
Structure of Protein Hormones: Signal peptides
Definition
  1. A short sequence of 15-30 hydrophobic amino acids located at the amino-terminal (beginning) of the proteins
  2. a signal sequence (S) directs the newly synthesized protein into the ER and then to export from the cell
  3. other proteins enter the cytosol and from there are directed to the mitochondria (M) or nucleus (N) or to other sites within the cell
  4. proteins move between the various compartments by vesicular transport
  5. uptake of proteins by particular vesicles is controlled by the sorting signal sequences in the proteins
Term
Structure of Protein Hormones: Prehormones
Definition
  • Newly synthesized protein hormones CONTAINING SIGNAL SEQUENCES
Term

Structure of protein hormones: Prohormones

(e.g. proparathyroid hormone)

Definition
  1. Peptide hormones synthesized as part of a larger precursor
    • (Proparathyroid hormone) the precursor of Parathyroid hormone
    • (Proinsulin) the precursor of insulin
    • (Proopiomelanocortin) is the precursor of several tropic hormones produced in the anterior pituitary.
    • Newly synthesized prohormone with a signal peptide is known as a preprohormone
Term
Why Prohomones?
Definition
  1. No health risk, minimal hormonal effect itself
  2. Enhances the strength (a ready supply, to be activated)
    • Prohormone Example: Pro-opiomelanocortin
  3. For peptide hormones, the conversion process from prohormone to hormone typically occurs after transport to the endoplasmic reticulum, requiring multiple processing enzymes. 
  4. For small molecule hormones, the conversion is often one step, and is often used to regulate hormone levels
Term
Structure of Protein Hormones: Glycoproteins
Definition
  1. Thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), and Luteinizing Hormone (LH), have sugar units attached to the amino-acid side chains
  2. After protein synthesis, the preprohormone moves from the ER moves to the Golgi apparatus, where sugar residues are attached to asparagine, serine and other amino-acid side-chains in a process called glycosylation
Term
The adrenal cortex produces what 2 types of steroid hormones?
Definition

Cortisol - A major glucocorticoid, promotes gluconeogenesis and fat & protein degradation.

 

Aldosterone - a major mineralocorticoid, increases absorption of sodium, chloride and bicarbonate by the kidney to increase blood volume and blood pressure

 

Term
Where in the adrenal cells does the synthesis of steroid hormones occur?
Definition
Smooth endoplasmic reticulum
Term
Synthesis of thyroid hormones
Definition
  1. Occurs in the thyroid gland
  2. Stimulated by thyrotropin (TSH) released from the anterior pituitary
  3. Thyrotropin is released in response to Thyrotropin Releasing Hormone produced from the hypothalamus in mammals (in birds, the MEDIAN EMINENCE is the primary source of TRH)
Term
Synthesis of thyroid hormones (continued)
Definition
  1. Thyroid hormones are synthesized by iodination of tyrosine residues in the thyroglobulin protein
  2. PROTEASES IN LYSOSOMES DEGRADE THYROGLOBULIN TO RELEASE THYROXINE (T4)
  3. T4 is converted to T3 (in the liver and thyroid) by selenium-dependent iodothyronine deiodinases
  4. T3 is metabolically more active than T4 in most animals, (but T3 and T4 are equally potent in birds)
Term
What are the 4 eicosanoid hormones?
Definition
  1. Prostaglandins
  2. Prostacyclins
  3. Thromboxanes
  4. Leukotrienes
Term
Where are eicosanoid hormones produced?
Definition
They are produced locally within the cell membranes and have autocrine and paracrine effects
Term
What do eicosanoid hormones do?
Definition

They:

  1. stimulate inflammation, 
  2. regulate blood flow 
  3. blood pressure, 
  4. affect ion transport, 
  5. modulate synaptic transmission
Term
What are eicosanoid hormones synthesized from?
Definition
20 carbon fatty acids, such as arachindonic acid (C20:4) delivered from membrane lipids
Term
What enzyme is important to eicosanoid hormone synthesis?
Definition
Cyclooxygenase (COX)
Term
Hormone Release: Steroids
Definition
Not stored, but released immediately to diffuse out of the cell
Term
Hormone release: Protein/peptide hormones
Definition
Stored in granules within the gland and are released in response to various stimuli
Term
Hormone Release: Tropic hormones
Definition

(they stimulate other hormone release)

  • TSH stimulates the release of thyroxine
  • FSH and LH stimulate the synthesis and release of adrenal steroids
  • ACTH stimulates the synthesis and release of adrenal steroids
Term
What environmental cues cause hormones to be released?
Definition

Light

smell,

sound,

temperature

Term
Neuroendocrine transduction: definition
Definition
neural stimulation of hormone secretion
Term
What hormones do plasma and intracellular glucose levels affect?
Definition

Glucagon

Insulin

Term
What hormones are involved with amino acid uptake?
Definition
somatotropin
Term
What hormones does the level of extracellular (blood level) calcium regulate?
Definition
Calcitonin and Parathyroid Hormone
Term
Where is the pituitary gland located?
Definition
in the "sella turcica" of the sphenoid skull. Below the hypothalamus
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