Exam III Flashcards
Vitamin D
- Steroid hormone
- Gets mobilized into an active form caled calcitriol
- Hypercalcemid by increasing Ca absorb in small intestine
Adenylate cyclase
- Enzyme in G protein system
- Turned on by G protein
- Takes AMP and makes cAMP
PTH and Bone
- Increase osteocytic osteolysis
- Increase osteoclast activity (slowly)
Addison’s Disease
- Decrease in cortisol
- Decrease HGO
- Decrease glycogen store
- Decrease adipose
- Decrease in muscle glycogen (weak)
- Decrease sympathetic response
- Skin darkening
- Decrease aldosterone (high K low Na)
Calcitriol
- Active form of vitamin D hormone
- Acts on intestine to increase Ca absorb
Alpha 1 Adrogergic Receptors + Cortisol
- Cortisol helps maintain
Sympathetic release of NorEpi –> Vasoconstriction
- Cortisol maintains receptor numbers so this response can occur
GLUT 4 and insulin
- Sugar transporter across the membrane
- Insulin takes GLUT4 from cytoplasm and places in membrane to increase transport
Zona Glomerulosa
- Makes aldosterone
- Regulated by renin angiotensin system
- ACTH help maintain Z.Glo
- Regulates kidney Na retention and K excretion
Feedback in Follicular Phase
- Follicles secrete estrogen
- Esterogen does positive feedback to HPA
- This positive feedback is responsible for the surge of LH at time of ovulation
Median Eminence
- Capillary bed at base of hypothalamus
- Neurosecretory neurones release hormones here
- Pick up hormones from hypothalamus and forms portal Vessel
Sarcomere purpose
- Generate Tension - Sarcomere = Striation
Nuclear Hormone Receptors
For steroid hormones
Pancreas Exocrine
- Ducts - Digestive enzymes and bicarb
Isometric Experiment
- Anchor one end of skeletal muscle and connect other end to a force transducer
- Length constant
- Add $ and measure tension
Skin darkening in Addison’s
- Decrease cortisol… less negative feedback in HPA
- Increase CRH
- Increase ACTH
- ACTH mimics hormone MSH (skin dark)
Prostaglandins
- Free fatty acids - Chains of carbon atoms with various subgroups that might have regulatory function
Three layers of adrenal cortex
Zona Glomerulosa
Zona Fasciculata
Zona Reicularis
Pars Intermedia
- Tissue that differentiates during development to make MSH
Serum Ca and Calcitonin
- Ca too high, Calcitonin released
G-Actin
- Globular proteins arranged in a double helix to form a filamentus actin
Ca Hormones
PTH
Calcitonin
Vitamin D
Oral Contracepties
- Small amount of estrogen and some progesterone
- Provides levels similar to luteal phase or early pregnancy
Slow Twitch Fiber
- Smaller diameter - Darker because of myoglobin - Fatigue resistant
Active Insulin
- Alpha and beta chains
GLUT 2
- Liver, pancreativ B cell, serosal surfaces of gut and kidney
- Low affinity for glucose
- Can also take up fructose
Starvation among plenty
Type I diabetes - High blood glucose but no insulin to get GLUT 4 to bring it into cells
Db/Db + Ob/Ob
obob loses weight
dbdb stays the same
Growth Hormone - Hyperglycemic
- Hyperglycemic
- Store of blood glucose in liver as glycogen… put into blood
- GH acts on liver to mobilize glyocgen and put into the blood
Cortisol and Kidney
- Increase renal blood flow
- Increase glomecular filtration
- Helps excrete H2O load
Muscle Contract
- Every myofibril and sarcomere is activated and shortens
Cortisol Paradox and Insulin
- Cortisol alone gives a true lipolytic response
- Modern western society: release cortisol but also get fed…. cortisol with insulin
- Some lipolytic behavior, but also have insulin
- Abdominal fat is particularly sensitive to insulin so even with low levels of insulin can get extra abdominal fat
Girls mature first because
- Hypothalamic axis matures first
T4 Actions
- Regulate metabolic rate
- Increase oxygen consumption
- Regulate body temperature
- Helps with normal growth and development
Actin Structural Proteins
- Nebulin - Titin
Anabolic Steroids
- Testosterone knockoffs
- Formulated to increase muscle stregnth
Men who take it:
- Decrease GNRH, LH, FSH –> shring testis
Women who take it:
- Experience liver and reproductive issues
Exophthalmos
- Hypothyroid
- Looks like eyes popping out of head
- Fluid and protein accumulation behind the eyes
Testosterone to Estrogen
- Acted upon by aramotase
Cretinism
- Lack of thyroid hormone when developing
- Physical dwarf
- Mentally compromised
Hormone Quantities
ng/mL 10^-9 g/mL
Insulin Receptor
- Has its own enzyme activity (kinase)
- Insulin binds, causes change
- Receptor undergoes autophosphorylation
- Starts a huge phosphorylation cascade
Sarcoplasmic Reticulum
- No ER in muscles - Stores Ca 2+
Gonadotropins
FSH and LH
Myosin Head
- Interacts with actins
- Forms bonds and rotates towards the center of the sarcomere
- Grab actins, pull them together… shorten sarcomere during contraction
- Contains Mg-ATP complex
- Contains ATPase Enzyme
- Head in couplets
DHP
- Dihydropyridine
- Signaled by action potential in T-Tubule
- Interacts with RyR protein in sarco. reticulum
Gigantism
- Over secretion of GH
- Inc. cell division in pit to make GH
- Pit grows but encased in bone… pushes on hypothalamus which pushes optic chiasm
- Vision problems
- Other issues…. adrenal, reproductive, high blood sugar
Decrease Iodine in Diet
- Decrease T3 and T4
- Increase TRH
- Increase TSH –> hyperplasia and hypertropy
Metabolizing FFAs
- Type I diabetes
- Increase ketone bodies in liver …. highly acidic (blown off as acetone)
- Ketones can lead to ketoacidosis
Glycosuria
- Kidney cannot handle excess glucose
- Glucose in urine… takes water with it
- People feel dehydrated and drink more
Testosterone to DHT
- 5-alpha-reductase reduces it to DHT
EOF Smooth Muscle
- 300x better than skeletal muscle
SEC
- Series eleastic compnenet - Tendons at the end
A Band
- Actin and myosin overlap - Each myosin surrounded by 6 actins
Glycogen Depletion
- Muscles run out of glycogen
- Need glycogen to fuel oxidative resp.
- People train to increase glycogen storage in muscle… run and then carb load!
Vitamin D in The Kidneys
- 1-alpha-hydroxylase (PTH positive feedback) act on Vitamin D3
- Released from kidneys as calcitriol
- Acts on intestines to increase Ca absorb
GHRH
Growth Hormone Releasing Hormone
- Increases GH
- Act on cells in pituitary to act on GH release
Male Target for LH
- Leydig cells
D Cells
- Islets of Langerhans - Make somatostatin
GH and growth
- Protein anabolic - Bone growth
Adrenal Medulla
- Inner adrenal gland
- Makes epinephrine
- Controlled by sympathetic nervous system
Vitamin D Synthesis in Body
IN LIVER
- Cholesterol → Vitamin D3 Precursor
Through blood to skin
- Absorb UVB light → Pre Vitamin D3
Return to LIVER
- Convert to Vitamin D3
Goes into blood to kidneys
Release of sperm
- Travel from epididymis through the ductus deferens
AA –> Glucose in Liver
- Need to deaminate
- Left with carbon atoms
- Turn carbons into glucose
- AA used move often is alanine
- If you see deaminating enzymes in the blood = liver damage
Endocrine regulation of Ca
- Ca is most highly regulated ion in the body
- 9-11 mg % in the blood
- Regulate via fast turnover
Treatments for Type II Diabetes
- Glucophage
- Oral insulin
- TZDs
- Fliptin DPP-4
- GLP-1 Receptor Agonists
- SGLT-2 Inhibitors
Type II Diabetes
- 95% of diabetics… adult onset
- Insulin resistance
- Obesity is a huge risk factor
- Have insulin but tissue does not responds to it
Stored form of thyroid hormone in blood
T4
Calcitonin
- From C cells in thyroid
- Calci tone down
- Peptide
- Hypocalcemic
- More important in juveniles
What happens in type I diabetes?
- High blood glucose
- Cannot turn on GLUT 4 to get glucose into cells
- Starvation amidst plenty
- Glucose spills into urine
- Cells metabolize free fatty acids
Bill Daughaday
- Tissue + radioactive S35
- Add GH… expect epiphyseal disc to grow and incorp S
- Nada… Repeat with same conditions + a piece of live - Incorporated!
- Liver is the difference… “Growth Mediator”
Suckling
- Milk letdown - Milk synthesis Oxytocin and Prolactin
Two Major Communication Systems in the Body
- Nervous - Endocrine
MSH
- Melanocyte stimulating hormone
- From pars intermedia
- No function in humans
- Lower vertebrates… change color of skin
Male Birth Control
- Treatment with progesterone and testosteron
- Pro: inhibits HPA
- Test: balances test
Type I Muscle
- Slow oxidative
- Mostly posture
- Resistant to fatigue
- High oxidative capacity (lots of mitochondria)
- Moderate SR activity
Functions of Testosterone
- Sperm development
- Maintainance and development of male reproductive tract
- Secondary sexual characteristics
- Central Nervous System
- Metabolic Hormone
Islet of Langerhans Cell Types
Alpha: glucagon
Beta: insulin
D: somatostatin
Muscle Type Transform
Cannot go 1 –>2 but can go from a and b and vice versa
A Band
- Anisotropic - More than one type of protein
Puberty and Bones
- Estrogen and Test stimulate bone growth –> spurt!
- At end, reach terminal height
- Epiphyseal disc disappears and becomes solid bones
Adipose tissue
- Responds to many hormones
- Secretes hormones
- talks to everyone!
- First hormone discovered from adipose tissue = leptin
Source of estrogen in postmenopausal women
- DHEA from adipose tissue
Decrease Calcium Release from SR
- When working hard, inorganic phosphate sneaks back into the SR via chloride channels,
- Phosphate binds up calcium and keeps it from being released
Rickets
- Vitamin D deficiency
- Either not enough in diet OR enough in diet but cannot be absorbed (not enough UVB)
- In juveniles leads to permanent bone deformation
- Adult verision is called osteomalacia
Causes of Fatigue
- Lactic Acid Buildup 2. Glycogen Depletion 3. Decrease in Ca release from SR
Ant Pit –> Thyroid
TSH stimulates thyroid
Rigor Mortis
- No ATP - Muscles are stuck - Cannot separate A and M
Treating castrated animal with inhibin
- Decrease FSH
- take extract from testicular lymph or rete testis
Protein / Peptide Hormones
- Most - Insulin - Growth Hormon - Prolactin - Generally water soluble
How do you get cAMP levels back down?
- Phosphodiesterase
- cAMP –> AMP
- Form of regulation is to regulate amount of PDE
ACTH
- Ant. Pit. - Adrenal hormones - Peptide
VMax dist. vs. load
- Vmax is a function of type of ATPase
Denervation Experiments
- Take muscle fiber
- Innervate from axon causes muscle contraction and also info for where to put ACh receptors
- Remove axon, ACh channels appear on surface of cell at points where there are no axons attached
Adrenal medulla + lungs
- Act on beta receptors… cause smooth muscle relaxation
Covalent Regulation
- Myosin kinase phosphorylates serines on myosin so it can bind to actin and form crossbridge
Actin Structure
- Formed from G-Actin in a double helix
- G actins form filamentus actin
- Troponin every 7 and tyopomyosin (regulatory proteins)
- Nebulin runs through the middle -
Titin helps stabilize Sarcomere
Adrenal Gland
- Sits on top of kidneys - Outer = adrenal cortex - Inner = adrenal medulla
Actin
- Thin filaments
Role of progesterone in male birth control
- Inhibits the HPA
Tyrosine Derivative Hormones
- Epinephrine
- Thyroxine
- Both are water soluble
Peroxidase
Enzyme that hook up iodines and thryoglobulin
Epididymis
- Where sperm is stored
- Final maturation process takes place here
Type I diabetes
- No insulin
- Juvenile
- Autoimmune
- antibodies to beta cells in pancreas
Hyperthyroid
- Too much thyroid hormone - Increase metabolic rate - Feel warm - Anxious, nervous
PDE
- Phosphodiesterase
- Degrades cAMP –> AMP
- Form of regulation is to regulate amount of PDE
Ca Pump
- Uses ATP
- Brings Ca into the SR and out of the cytoplasm
- Decrease [Ca] in cytoplasm
Glucagon and Liver
- Increase glycogenolysis
- Increase gluconeogenesis
- Increase protein catabolism
Hyperglycemic hormones
GH
T4
T3
Cortisol
Epinephrine
Glucagon
Two uses of ATP in muscle
- Hydrolyze and use energy in phosphate bond to rotate head
- Use fresh ATP sterically to to separate actin from myosin
Thyroid Hormone Synthesis
- Take iodine out of blood and bring into cell
- Na symporter moves I into cell
- Pendrin transporter moves I into the colloid where peroxidases put thyroglobulin
- Tyrosines attach
- Couple Iodine to tyrosines
- Now have thyroglobulin and iodines
- Draw thyroglobulin into the cell and use enzyme to cleave T3 and T2 and put in blood
Neurosecretory Neurons
- Long axons - Terminate in post. pituitary - Neurohemal… post pit
Luteal Phase
- Signaled by LH surge
- Estrogen and Progesterone
- Progesterone provides NEGATIVE feedback on HPA… keeps FSH and LH low
Epipen
- Makes bronchioles dilate
Insulin resistance location
- Can develop at any point along the phosphorylation cascade
H Zone
- Myosin alone with no actin - Heavy
Sarcomere length and muscle velocity
- Small sarcomeres lined up have to work less hard - Long sarcomeres lined up work harder
What does smooth muscle do?
- Sphincters - GI tract - Vaso constriction/ dilation
Where progesterone acts
- Hypothalamus
- Acts indirectly on the neurons that make GnRH
- GnRH neurons connected to the rest of the brain by other neurons
- Progesterone acts on those
GLUT 3
- Brain neurons and tissue
- High affinity for glucose
Regulatory Ion of Smooth Muscle
Calcium 2+
Biological Clock
- Regulated by hypothalamus - Secretion of cortisol is expression - Part of circadian rhythm
Posterior Pituitary Origin
- Outgrowth of hypothalamus
PTH and Kidneys
- Increase Ca reabsorption
- Decrease Ca in urine
GLP 1
- Glucagon like peptide - Incretin
Cortisol and time of day
- Biological clock - Fluctuate over 24 hours - High 4am to 8am… prepped metabolically for the day
Osteoblast
- Builds bone… lays down new bone
- On the outside of the osteon… goes through maturation and works its way inward
- Matures into osteocyte
Vasopressin
- Post. Pit - Acts on blood vesses (esp. arteries) - Causes constriction which helps to increase blood pressure
How testis make testosterone
- Leydig cells
- Testosterone diffuses out of leydig cells into Semineferous Tubules to help with maturation of sperm
- Diffuses into blood too
Z- Line
- Proteins that differentiate the end of the sarcomere
Sertoli Cell
- Make inhibin
- Interact with spermatogonia
Taking GH…
- Cannot take orally - Inject in blood - Because protein
Euthyroid
- Normal thyroid hormone - important for…. Metabolic Rate Oxygen Consumption Body Temp Effects on the CNS
Myofibril
- Long thread of protein - 1-2 microns in diameter - Runs end to end - Made up of sarcomeres
Type IIa Muscle
- Fast Oxidative
- More red
- Fast ATPase
- More capillaries
- More ox capacity
- High SR activity
- In runners
Master Gland
- Old name for anterior pituitary
Infundibulum
- Connects pituitary and hypothalamus
GLUT 5
- Fructose transporters in small intestine
- Medium affinity for glucose
Dwarfism
- Unde secretion of GH - Can correct now with biotech
Sarcomere Contraction
- A band stays the same
- I band gets shorter
- H band gets shorter
Blood sugar regulation hormones
- Insulin
- Glucagon
Sarcolemma
- Muscle fiber membrane
CaM
- Calmodulin
- Can bind 4 Ca
- Removes caldesmon and calponin regulatory proteins
MHC Gene
- Type I diabetes - Major histocompatibility complex
Two main hormones of Posterior Pit.
- Oxytocin - Vasopressin
Glucose Intolerance
- Type II diabetes
- Do not handle glucose well
What causes insulin secretion?
- Increase blood glucose (after you eat)
- Increase AA
- Increase in Vagal activity
- Incretins
Prolactin
- Ant. Pit
- Hypothalamus signals release
- Acts on mammary tissue to stimulate milk synthesis
Cortisol and immune effects
- Decrease allergic response
- Decrease ability to form antibodies
- Decrease histamine (from MAST cells) – anti inflammatory
Three major hormones with Ca regulation
PTH
Calcitonin
Vitamin D
How peptide hormones get into cells
- Cannot cross membrane
- Binds receptor
- Receptor does signal transduction
Ketoacidosis
- Acidic blood pH - too high –> coma - Will cause death if untreated
Adrenal Medulla and Heart
- Chrono and ino
- Increase cardiac output
- Increase coronary blood flow
- Act on beta adrenergic receptors
- Increase BP
Hypothalmus to Ant. Pit
- TRH stimulates ant pit
GH and Protein Anabolic
- Increase protein synthesis
- As you grow, muscles and organs get bigger because laying down protein
- Need energy to promote growth
TRH
- Released by hypothalamus
- Stimulates production of TSH in anterior pituigary
- Negative feedback from T3 and T4
Four Major Classes of Receptors
- Nuclear Hormone Receptors (for steroids)
- Ligand-Gated Ion Channels
- G-Protein Coupled Receptors
- Enzyme linked receptors
Adrenal Medulla
- Extension of sympathetic nervous system
- Release epinephrine
T-Tubules
- Connective tubule system in muscle fiber
Bone Growth
- From epiphyseal plate - Cartilage - Then ossified
Oxytocin + Uterus
- Birth
- Oxytocin speeds up strength of uterine contraction
- Receptors in greater intensity near top of uterus, less at bottom (proper movement DOWN)
LH
- Ant. Pit. - Luteinizing hormone - Peptide
Metformin (Glucophage)
- Type II Diabetes Treamtn
- Degrease HGO
- Increase insulin sensitivity in peripheral tissues
Glucagon and Adipole Tissue
- Lipolytic… promote lipolysis
Osteon
- Turns over bone - Every 11 months
Thryoid to Blood
- T3 and T4
- Negative feedback to stop TRH
Signal for muscle to contract
- Increase in Ca in the cytoplasm …. above 10^-7 Molar
Aldosterone
- Z. Glo
- mineralcorticoid
- Regulates Na and K
- Acts on kidney
- causes Na retention
- causes K excretion
Treatment for Type I diabetes
- Administer insulin
Growth Hormone
- Somatotropin 2 Actions: Metabolic, Growth
Alpha Cells
- Islets of Langerhans
- Make hormone glucagon
Osteoclasts
- Macrophages from the immune system
- Invade bone and result in serious bone resorption
Regulatory Proteins in Smooth Muscle (Actin)
- Caldesmon
- Calponin
Hyperglycemic
Increase blood glucose
Testosterone Inhibits
Hypothalamus (GNRH)
Anterior Pituitary (FSH and LH)
No tetanus in heart… why?
- Cannot bring a second electrical stimulus - Good!
Creatine phosphate
- Take a phosphate and donate it to ADP to help regenerate ATP in muscle
Glucose tolerance test
- Come in fasted
- Monitor blood gluocse over time
- Drink sugary drink
Thyroid Colloid
- Inside - Stored thyroid hormone
Cortisol Actions
- Metabolic hormone
- Immune effects
- Cardiovascular system
- Bone
- Kidney
GLUT 1
- Brain vaculature, RBC, all tissues
- High affinity for glucose
I-Band
- Isotropic… just one type of protein
Cortisol as a metabolic hormone
- Hyperglycemic
- Increase lipolysis
- Decrease glucose utilization
- Decrease insulin sensitivity
- gluconeogenic
Resistin
Generates insulin resistance
Mechanism of Smooth Muscle Contraction
- Release NT around varicosity… diffuse into cell
- Ca into the cell and binds to CaM
- CaM removes caldesmon and calponin from actin
- Myosin kinase phosphorylates serines on myosin
- Phosphorylated myosin binds to actin and forms crossbridge
- Phosphatase enter and remove phosphate off myosin so A and M can detach… system reset
Glycogen
- Stored glucose - Break it down into glucose - Need glucose for anaerobic component
Adult Rickets
Osteomalacia
- Weak bones
- Malformations
Increase # Mito in Cells
- Especially endurance trainging - Also increases metabolic rate
External Development of Male Genitalia
- From DHT
Sertoli Cells
- Make inhibin
- Involved in sperm maturation
- keep track of number of sperm being made
- Communicate sperm number to pituitary via inhibin
Intracellular Receptor
- Receptor inside the cell
- Steroid hormones
- Act on nucleus
Change gene transcription
Zona Fasciculata and Zona Reticularis
- Make a glucocortiocid (mainly cortisol) - Also cortisone and corticosterone
ADH and Vasopressin Work Together
- Dehydration = lower blood volume… decrease blood pressure
- Secrete ADH to conserve water… increase BP
- Vasopressin also increases BP
Polyurea
- Increase urine flow
Neurohemal
- Release hormone to blood - Posterior pituitary
Active form of Vidamin D Hormone
- Calcitriol
- From reaction of vitamin D3 and 1-alpha- hydroxylase in kidneys
Maximum tension in a WHOLE muscle depends on
- Recruitment of motor units 2. Size of motor units
PTH and Intestine
- Helps Vitamin D action with Ca absorption
Actin and Myosin in Smooth Muscle
- Set up like mesh inside cell
- Have protein anchors in cell membrane and cytoplasm
- Sarcomeres attached
Steroid Hormone Receptors
Ligand activated site specific DNA binding proteins
- in cytoplasm
- Hormone enters cell via membrane diffusion and brings the compex to the nucleus
- Regulates gene transcription (turns on and off genes)
Leptin in humans
- Amount of leptin in blood is proportional to fat tissue
- As body fat increases, amount of leptin increases
- If leptin levels too low, can stop reproductive cycle in women
- Too high get leptin resistance
Bones and Ca
- Calcium storage
Sarcomere at Resting Length
- Optimized a/m overlap - Optimized # crossbridges
Serum Ca and PTH
- Decrease Ca, Increase PTH
Titin
- Structural protein in actin - Provides elasticity - Stabilize sarcomere Z to Z
DHEA
- Dehydropiandosterone
- Male like hormone
- From Zona Reticularis
- Can be metabolized to testosterone
- Test –> est in adipose tissue
- In postmenopausal women… source of DHEA available throug DHEA… why a little adipose tissue is good!
Pituitary Gland (Hypophysis) Location
- Lies in sella turcica - Outlet to brain via hypothalamus by infundibulum - Anterior and Posterior
Things that use calcium
Nerves
Synapses
Muscle
Pendrin
- Transporter that moves iodine into the colloid
Hypoglycemic Hormones
Insulin
Spermatogonia
- Immature sperm
- Hang out along the edges of the smineferous tubules
- Move in as they mature into spermatids
- In close contact with sertoli cells
ACTH on Kidney
Maintain Z. Glo
Path of hormone in post. pit.
- Made at cell body
- Transport down axon
- Into blood
Cushing’s Disease
- Elevated Cortisol
- Increase HGO
- Muscle weakness
- Increase urea production
- Central obesity
- Easily bruised skin
- Increase response to sympathetic activation
- Hypertension
- Increased mieralcorticoid activity (aldosterone)…. increase Na retention, decrease K levels
Optic Chiasm
- Info from one eye to another - Right by hypothalaus
FSH and Testis
- FSH stimulate sertoli cells
- Sertoli cells involved in sperm maturation
- Sertoli cells keep track of number of sperm being made… communicate that to the pituitary via inhibin
Anaerobic Threshold
- Has to do with metabolizing lactic acid - More you train, the better your liver gets at the cori cycle
Smooth Muscle Morphology
- Increase surface to volume ratio (high surface area per volume)
- Small cells (2-5 micron diameter)
- 100-400 micrometers long
Which is more active, T3 or T4?
T3
Crossbridge Formation
- Ca levels increase
- Ca binds to troponin
- Tropo-Ca pulls toptomyosin away from actin’s myosin binding site
- Myosin binds to active and completes power stroke
- Actin filament moves
Fasting Glucose
- Good indicator of glucose tolerance level
- Normal… 100 mg % or below
- Intolerant is around 125 mg %
How to get Type I Diabetes
- Gene
- Virus… immune system responds and makes antibodies for beta cells in pancreas
- immune system destroys beta cells over months
Leydig Cells
- Make testosterone
Isotonic Study
- muscle anchored to a displacement transducer and weight pan
How steroid hormones get into cells
- Can move in via cell membranes
- Bind an intracellular receptor
- Acts on nucleus
- Change in gene transcription
Cortisol and Bones
- Decrease osteoblast activity
- Decrease new bone formation
Somatostatin
- From D cells
- Turn off secretion of glucacgon and insulin
Cortisol and cardiovascular system
- Maintain alpha 1 receptors for norepinephrine
Anterior Pituitary Origin
- Tissue buds developmentally from roof of mouth
Increase [Ca] in cytoplasm
- Calcium binds troponin
- Change shape troponin
- Change shape of tropomyosin
- Tropomyosin slides away and allows myosin head to interact with actin
- Finish hydrolyzing ADPPhosphate to ADP +Pi …. use energy to rotate head and move actin
What hormones actually do
- Change rate function within the target cell
Testosterone and Central Nervous System
- Sexual behavior
- Libido
G-Protein Coupled Receptor Names
GPCR or 7TM
Load and muscle velocity
- Greater load, lower speed
things that can influence muscle velocity (speed of contraction)
- ATPase type
- Load
- Sarcomere length
Polydipsia
- Drink more
Decrease in cortisol HPA axis
- Less negative feedback for HPA axis
- Increase CRH from hypothalamus
- Increase ACTH
Myxedema
- Fluid accumulates under the skin - Due to accumulation in glycoprotein - Hypothyroid
Troponin C
-Subunit on troponin to which Ca binds causes a conformation change
Oral Insulin
Causes beta cells to secrete more insulin
Adrenal Medulla Target Tissues
- Heart
- Skeletal Muscle
- Adipose Tissue
- Liver
- Lungs
Fast Twitch Fiber
- Larger diameter - Pale color - Fatigue easy
Phases of the ovarian cycle
Follicular (first 14 days)
Lutela (last 14 days)
Paracrine Regulation
- Cells talk to neighbors (diffusion) - I.e. Gonad
Growth Hormone + Metabolic
- Hyperglycemic - Lipolytic
Osteopetrosis
- When bone does not turn over
PTH
Parathyroid hormone
- Hypercalcemic (increases plasma Ca)
- Peptide hormone
Growth Hormone - Lipolytic
- Store fats as triglycerides - Break down trigylcerides into FFA
Hyperplasia
Increase cell size Exhibited in muscles
TSH
- Ant. Pit. - Thyroid Stimulating Hormone - Peptide
Calcitriol
Active form of Vitamin D
Hypercalcemic
Adipose tissue + adrenal medulla
- Lipolytic
- Beta receptor
Castrated Animal
- Removes testosterone
- Increase in FSH and LH
- If you treat with tesosterone…. decrease LH but not FSH
Hypothyroid
- Not enough thyroid hormone - Decrease in MR - Feel tired, cold - Depression, fatigue
Two types of ATPasw
- Fast - Slow
Three forms of testosterone at cellular level
- testosterone
- becomes DHT
- becomes estrogen
Gh and Bone Growth
Stimulates bone growth - Growth plate - Maturation
Effects of Hemicastration
- Initial increase in FSH
- Remaining teste undergoes compensatory hypertrophy
- Eventually get a decrease in FSH as sperm production increases
- Increase sperm production increases inihibin which decreases FSH
Timing for Hormones
- Steroids… take a few hours
- cAMP is FAST, minutes
Reinnervation Experiments
- Take type I cell
- Remove type I axon and re innervate with type II
- Cell is now type II
- Re innervation happens at ACh receptor site
- Can do same thing in reverse…
Relaxed State Myosin Head
- Myosin head cocked
- Close proximity of myosin head and actin
- ATP is partially hydrolyzed
Acromegaly
- Over secretion of GH in adult
- Hands, face, feet respond… disfigurement
- Can be caught early
- Metabolic issues too
ob/ob mouse
- Homozygous… becomes obese
- Parabiose with normal, gets thin
- Tells us there is something in the blood that makes it obese
- Jeffrey Friedman… discovered leptin
- OBOB has defective leptin
- Gets normal leptin from the normal mouse
F- Actin
- Filamentus actin - Made of double helix of G-Actin
Type IIb Muscle
- Fast Glycolytic
- White fibers
- Easy fatigue
- Low ox capacity (fewer mito)
- High SR activity
Maximum tension in a muscle fiber (cell) depends on
- Number of cross bridges formed
- Muscle length
- Muscle type (fast or slow due to ATPase)
Cortisol Metabolic Actions
- Hyperclycemic
- Increase lipolysis
Autocrine Regulation
- Cells talk to themselves - Release peptide or something and bind to cells to change and do something else
Norepinephrine receptors
alpha
Protein Turnover in Skeletal Muscle
- Every 6 Weeks or so
Osteocyte
- Mature osteoblast
- Causes bone resorption (take away Ca)
aka osteocytic osteolysis
Actin Regulatory Proteins
Troponin (every 7 G actin) Tropomyosin
Distance Shortened vs. Time
- Dist/Time = Velocity
Stress
- Make cortisol when stressed
Oxytocin + Breast Tissue
- Infant suckle sends signal to hypothalamus
- Stimulates neurosec. neurons which end in post. pit
- Release oxytocin to blood –> mammary gland
- Milk letodwn
Hyperinsulinemia
- To get over insulin resistance, body makes excess insulin
- Type II diabetes
Goiter
- Increase TSH - Hyperplasia and hypertrophy
Anterior Pituitary Overview
- Celles are distinctly separate
Ghrelin
- Act on hypothalamus to increase appetite
- Also increase GH
- GH = hyperglycemic…. Ghrelin released when blood sugar is low
PTH
- Secreted when Ca levels are low
- Acts on…
Bone
Kidney
Intestine
Feedback in Luteal Phase
- Progesterone provides negative feedback on the HPA
- Keeps FSH and LH low
HPA Axis
Hypothalamus
CRH (+)
Anterior Pituitary
ACTH (+)
Adrenal Cortex
Cortisol (- on ant. pit, hypo)
Graves Antibody
- Agonist
- Used to be called LATS (long acting thyroid stimulator)
- Made in immune system
- Causes decrease in TRH and TSH
Why do anabolic steroids shrink testis?
- Decrease GNRH, FSH, and LH
What training does
- Increase glycogen storage
- Increase # mitochondria in muscle cells
- Increase anaerobic threshold
Oxytocin
- Peptide - Smooth muscle contraction - Breast tissue + uterus
Isotonic
- Constant tension - Measure muscle shortening
Cortisol on skeletal muscle
- Causes protein catabolism
- Release AA into blood
- AA circulate to liver where convert to glucose
Gluconeogenesis
Renin Angiotensin System
- Regulates K levels
Epinephrine receptors
beta
Synthroid
Mix of T3 and T4
How G Protein System Works
- Hormone binds receptor stimulating G Protein
- G protein turns on adenylate cyclase… takes AMP and makes cAMP
- Increase levels of cAMP in cell
- cAMP binds protein kinase which phosphorylates proteins
Leptin
- Peptide hormone
- Made when adipose tissue sees glucose
- Goes into blood and acts on CNS (hypothalamus)
- Decreases level of NPY neurotransmitter… decreases appetite
HGO
- Hepatic glucose output
Seminiferous Tubules
- Where sperm are made in the testis
- Can see spermatogonia on the outside
- As they mature, move into the tubules and become spermatids
Healthy blood sugar level
100 mg %
RyR
- Protein in sarcoplasmic reticulum
- Activated by DHP
- Opens calcium channels…. Ca leaves SR and dumps into cytoplasm
Osteocytic Osteolysis
- Osteocytes cause bone resoprtion… remove Ca
- Every 11 months Ca is turned over
Economy of Force Equation
EOF = Force * Time/ATP Used
Beta Cells
- Islets of Langerhans - Make insulin
Glucagon
- Peptide hormone from alpha cells
- Secrete when blood glucose low
- Acts to bring up blood sugar
- Targets: liver and adipose tissue
Tissues involved in Ca Regulation
Bone
Small intestine… absorb
Kidney… excrete
GLUT 4 Location and Km
- Muscle, fat cells
- Medium affinity for glucose
Gene in type I diabetes
- MHC Gene - 50%
M-Line
- Middle of the mysoin
Caveolae
- In-folds on smooth muscle membrane - Conserve Ca and increase surface area
Other types of regulation that are not endocrine
- Paracrine - Autocrine
Zona Reticularis
- Make DHEA
Testosterone as a Metabolic Hormone
- Anabolic
- Increases protein synthesis
- Increase # RBC
- Testosterone is lipolytic
- Promotes closure of the epiphyseal disc during puberty
ACh –> Contraction
- AP down motor axon releases ACh….
- ACh binds to nicotinic Channel (increase g Na and g K –> LCF –> AP in muscle membrane)
- AP sent down T-Tubule and stimulates DHP
- DHP interacts with RyR… open Ca channels, Ca into cytoplasm
Osteon
Functional group of the bone
- Osteoblasts
- Osteoclasts
- Osteocytes
Testosterone and Secondary Sexual Characteristics
- Distribution of body hair
- Deepening of boice
- Acts on sebaceous glands…. overstimulation = acne
Somatomedin Hypothesis
- “Growth Mediator” - Ant. Pit. releases growth hormone which acts on the liver which makes IGF-1
Daughaday Flaw
- Wasn’t sensistive enough
- TH… backup system to make bone grow
- IGF in blood negative feedback tohelp regulate growth hormone Much more complex than he gave credit for
Axon and Muscle
- Stimulates contraction of muscle - Gives cell information abuot what type of muscle cell it is going to be - Set up in development
Somatostatin Effects on GH
Decrease GH
Incretins
- From GI tract (intestine)
- 2 peptides (GLP1 and GIP)
- Causes insulin secretion
Calcium Absorption in Small Intestine
400-500 mg Ca in the GI tract per meal
Jet Lag
- Travel faster than your biological clock
Protein Anabolic
- Increase protein synthesis
Islets of Langerhans Cell Types
- Alpha - Beta - D
Steroid Hormones
- 27 C, based on cholesterole - Modified through series of enzyme reactions - Not very water soluble
Follicular Phase Overview
- First 14 days
- Follicles develop in ovary
- Peak of FSH promotes follicular development
- Follicles make estrogen (increase estrogen)
Achondroplastic Dwarf
- Have GH
- Lack specific fibroblast growth factor receptor 3
- Normal head, hands, fet
- Short torso
Calcitonin
- Hypocalcemic
- Secreted when there is an increase of Ca in plasma
- Acts on one
- More important in juvelies
Thyroid Structure
- Up along windpipe - L and R lobes - Connects by ismus - Follicle cell layer - Inside is the colloid
Initiation of contraction
- ATP fully hydrolyzed to ADP + Pi
Nutrition and Growth
- Nutrients –> liver
- Good nutrition more IGF-I
- Growth
- Connection between endocrine control, growth, nutrition
Isometric
- Keep length of muscle constant - Measure tension development
Pancreas Endocrine
- Blood Islets of Langerhans
Adiponectin
- Hormone from adipose tissue
- Target is skeletal muscle
- Increase insulin sensitivity in skeletal muscle
Estrogen and Testosterone act more on….
LH
Calcitonin and Bone
- Decrease osteocytic osteolysis
- Decrease osteoclast formation
Nebulin
- Structural protein in actin
- Runs through the middle
- Helps align actin
Action potential in cardiac muscle
- LONG - Couple of hundred msec - Heart muscle cannot tetanize
Adrenal medulla + liver
- Increase glycogenolysis
- Increase HGO
Hemoglobin A1C
- Glycosylated hb
- non eznymatic glycation
- Test shows glucose control over a long period of time
Normal: 5.7% or below
Prediabetic: 5.7- 6.4%
Diabetic 6.5% +
Why is calcitonin likely more useful for juveniles?
- Higher Ca in diet
Frank-Starling
- FOC proprotational to amount of blood
- More blood, more stretch
- Get slightly betwtter A/M overlap and crossbridge
- With heart stretch, better overlap, more cross, more force!
Oxytocin in Males
- Smooth muscle contraction in reproductive tract for ejaculation of sperm
Insulin Basics
- Peptide hormone
- 1 long chain
- Proinsulin –> active form
Adrenal Cortex
- Outer adrenal gland - Makes steroid hormones - Three layers = Zonas…. glomerulosa, fasciculata, reticularis
ADH
- Post. Pit. - Antidiuretic Hormone - Acts on kidney to decrease urine flow and increase water retention
Tetanus
- Given enough stimulation to complete a full smooth contraction
FSH
- Ant Pit - Follicle stimulating hormone - Peptide
Anterior Pituitary Hormones
FLAT PiG (All peptide)
FSH
LH
ACTH
TSH
Prolactin
GH
Three organs in type II diabetes
Liver
Skeletal muscle
Adipose Tissue
Visceral Smooth Muscle
- Gap junctions… transmit electrical signals from cell to cell
- Can contract spontaneously (one cell contracts and others follow in wave)
- Less innervation than multi
What Coffee Does
- Inhibits PDE
- Increase urination
- Increase glomerular filtration rate in kidneys
- Boost liver, increase glycogen
Stress and muscle cells
- Training makes your muscles BIGGER … does not change the number of cells, just increases the number of myofibrils
Where do you get ATP
- Glycosysis - Oxidative phosphorylation
Central obesity
- Symptom of Cushing’s
- Deposits of fat around central part of the body
- Oftentimes striations
Male Endocrine System
Hypothalamus
- GNRH
Anterior Pituitary
- LH
- FSH
Testis
- Testosterone (negative on Ant.Pit. and Hypo)
- Inhibin (Decrease FSH)
Classical Divisions for Smooth Muscle
- Multi Unit - Visceral
Third source of ATP for muscle
- Creatine phoshphate can take phosphate and donate it to ADP to help regenerate ATP pool
- Resting while working out… regenerate ATP pool with creatine phosphate
Nursing as Birth Control
- While nursing, decrease production of LH and FSH - No ovulaiton
Graves Disease
- Autoimmune
- Body makes antibody that acts on TSH receptor
- Antibody is an agonist
- Increase T3 and T4… hyperthyroid
- Diagnose by measuring T3, T4, and TSH
Myosin
- Thick filaments
Lactic Acid Buildup
- Contributes to fatigue - Not the whole story
Multi Unit Smooth Muscle - Iris
- External stimulus for contraction
- No action potential
- Let Ca do its thing
Timing of muscles
- Lag time between electrical signaling and when you see tension
Db/Db Mouse
- Obese and diabetic
- Parabiose to normal mouse
- Stays obese
- Defective leptin receptor
X-int of Velocity vs. Load
- Reflects number of crossbridges
Negative Feedback Example
- T3 and T4 negative feedback on hypothalamus - Stop TRH
What signals the start of the luteal phase?
- Estrogen from follicle cells –> HPA –> secrete LH
Metabolic Syndrom Consequences
- Increase cardiovascular disease
- Decrease wound healing
- Increase kidney disease
- Increase blindness
- Increase nerve pain (due to decrease myelination)
Lipolytic
Mobilize free fatty acids
Thyroid Biochemistry
- Tyrosine coupled with another tyrosine to make hormones - 3 Iodine …. T3 - 4 Iodine… T4
Proinsulin
- Three sets of disulfide bonds that form this structure - Clip off C peptide to make active
Contractile componenets
- Actin, myosin, crossbridge cycle
Breaking up Actin and Myosin
- Bring in fresh ATP - Causes a steric change that will allow you to separate them - Partially hydrolyze it… next cycle!
NPY Neurotransmitter
- Acted on by leptin
- Controls appetite
- Decrease NPY, decrease appetite
Metabolic Hormone
- Increase protein synthesis
- Hyperglycemic
- Lipolytic
- Energy mobilizer
Different Biochemical Hormone Types
- Tyrosine Derivative
- Steroid
- Protein/Peptide
- Prostaglandins
Adiponectin and Fat
- Increase fat, decrease plasma adiponectin
- Skeletal muscle become insulin resistant
Renal blood flow
Blood flow to the kidneys
Role of reproductive endocrinology in males
- Produce sperm
- Produce testosterone
Endocrine System Overview
- Hormones from glands
- Small quantities
- Circulate and act on target tissue
- Broad and specific
Inhibin Inhibits (Male)
FSH
What defines a target tissue?
RECEPTORS
GIP
Glucose independent insulinotrophic peptide - Incretins
Metabolic Syndrome
- Type II Diabetes is an example
- Hyperinsulinemia
- Insulin resistance
- Glucose intolerance
- Hyerlipidemia
- Hyertriglyeridemia
- Hypertension
Beta Cell Exhaustion
- From hyperinsulinemia
- Beta cells just wear out
- Type II diabetes
Heterolagous Disease
- Multiple sources or causes result in the same clinical picture
- I.e. Type II Diabetes
Tension vs. Freq
Y: Tension
X: Freq
Twitch –> wave summation –> tetanus
G- Protein Receptors
- Receptors coupled to G proteins
- Signal transduction starts with G protein
- Uses cAMP as a secondary messenger
IGF-I
- Insulin like growth factor 1
- Peptide
- Similar to insulin
- Acts on bone causing it to grow
- Bone itself also makes IGF-I and can act in autocrine paracrine matter
- GH can act on bone too
Prednisone Taper
- Large dose of cortisol…. decrease CRH, ACTH, cortisol from body
- If you come off too quickly, do not have own cortisol
- Decrease alpha-1 receptors, decrease blood pressure, pass out.
Working out and muscles
- Stress muscles
- Micro tears
- Lay down more protein/ number of myofibrils and sarcomeres
- Increasing number of sarcomeres in parallel and increase ability to generate tension
Smooth Muscle Cell
- Long and small
- Nucleated
- No SR
- No T Tubule
- No troponin and tropomyosin
Insulin Actions
- Increase cell permeability to glucose
- Increase glycogen storage in the liver + skeletal muscle
- Decrease gluconeogensis
- Increase AA transport into cells
- Increase lipogeneiss in adipose
- Increase K into cells
Motor Unit
Motor neuron and the skeletal muscle cell/fiber it innervates… the size of the motor unit varies
Thyroid responds to increase TSH by
- Hyperplasia and hypertrophy
- Increase cell number and size
- GOITER
Hashimoto’s Disease
- Immune system makes antagonistic antibody to block TSH receptor
- Decrease T3 and T4
- Sluggish and fatigued
- Increase TRH and TSH
- With extra TSH to act on thyroid… possible for TSH to outcompete antiboid
- Hypothyroid in waves
- When negative feedback kicks in go euthyroid
- More antagonist go to hypo
Sliding filament theory
- Myosin heads pull actin together… shorten sarcomere - Contraction
Skeletal muscle + adrenal medulla
- increase blood flow - increase beta adrenergic receptors
Girls mature first because
- Hypothalamic axis matures first
Gluconeogenic
- Make glucose from new sources
Deiodinase
- Enzyme - Converts T4 to T3 - Can make active form of hormone in target tissue
