Endo Corino
-
Upload
bruno-mora -
Category
Documents
-
view
20 -
download
2
Transcript of Endo Corino
Endocrine system
Dr. Victor J. Samillan
ES and Homeostasis• Homeostasis
Tissues can be targeted by multiple hormones
Hormones can act synergistically, permissively, or antagonistically
Synergistic effects of hormones on blood glucose concentration
Peptide Hormones
Synthesis/transport/half-life
Storage?
Multiple processing patterns for protein hormones
Hormone-Receptor interactions• Definition: a protein that binds a ligand with high
affinity and low capacity. This binding must be saturuable.
• A tissue becomes a target for a hormone by expressing a specific receptor for it. Hormones circulate in the blood stream but only cells with receptors for it are targets for its action.
Agonist vs. Antagonist• Agonists are molecules that bind the receptor
and induce all the post-receptor events that lead to a biologic effect. In other words, they act like the "normal" hormone, although perhaps more or less potently
• Antagonists are molecules that bind the receptor and block binding of the agonist, but fail to trigger intracellular signaling events
Metabolic clearance rate (MCR)
• Defines the quantitative removal of hormone from plasma
• The bulk of hormone is cleared by liver and kidneys • Only a small fraction is removed by target tissue
• protein and amine hormones bind to receptors and are internalized and degraded
• Steroid and thyroid hormones are degraded after hormone-receptor complex binds to nuclear chromatin
• 99% of excreted hormone is degraded or conjugated by Phase I and Phase II enzyme systems
MCR of some hormones
Hormone Half-life
Amines 2-3 min
Thyroid hormones: T4 T3
6.7 days0.75 days
Polypeptides 4-40 min
Proteins 15-170 min
Steroids 4-120 min
Methods of intercellular communication by secreted molecules
(a) Endocrine signaling
Bloodvessel Response
Response
Response
Synapse
Response
Response
(b) Paracrine signaling – short distances
(c) Autocrine signaling – short distances
Neuron
(d) Synaptic signaling
Neurosecretorycell
Bloodvessel
(e) Neuroendocrine signaling
Different receptorsSame receptors but differentintracellular proteins (not shown)
Different cellularresponses
Different cellularresponses
Epinephrine Epinephrine Epinephrine
receptor receptor receptor
Glycogendeposits
Vesseldilates.
Vesselconstricts.
Glycogenbreaks downand glucoseis releasedfrom cell.
(a) Liver cell (b) Skeletal muscleblood vessel
Intestinal bloodvessel
(c)
Figure 45.9
Types of receptors
Second messengers for cell-surface receptorsSecond messenger systems include:
Adenylate cyclase which catalyzes the conversion of ATP to cyclic AMP;
Guanylate cyclase which catalyzes the conversion of GMP to cyclic GMP (cyclic AMP and cyclic GMP are known collectively as cyclic nucleotides);
Calcium and calmodulin; phospholipase C which catalyzes phosphoinositide turnover producing inositol phosphates and diacyl glycerol.
Hormones and their receptors
Hormone Class of hormone
Location
Amine (epinephrine)
Water-soluble Cell surface
Amine (thyroid hormone)
Lipid soluble Intracellular
Peptide/protein Water soluble Cell surface
Steroids and Vitamin D
Lipid Soluble Intracellular
Binding vs. biological response
Spare receptors Amplification by 2nd messenger
Spare Receptors• Maximum response with 2-3% receptor
occupancy• 97% of receptors are “spare”• Maximum biological response is achieved when
all of the receptors are occupied on an average of <3% of the time
• The greater the proportion of spare receptors, the more sensitive the target cell to the hormone
• Lower concentration of hormone required to achieve half-maximal response
Spare receptors• In most systems the maximum biological
response is achieved at concentrations of hormone lower than required to occupy all of the receptors on the cell.
• Examples: • insulin stimulates maximum glucose oxidation in
adipocytes with only 2-3% of receptors bound• LH stimulates maximum testosterone production in
Leydig cells when only 1% of receptors are bound
Control Pathways and Feedback Loops
• There are three types of hormonal control pathays
Pathway Example
Stimulus Low bloodglucose
Receptorprotein
Pancreassecretesglucagon ( )
Endocrinecell Blood
vessel
LiverTarget
effectors
Response
Pathway Example
Stimulus Suckling
Sensoryneuron
Hypothalamus/posterior pituitary
Neurosecretorycell
Bloodvessel
Posterior pituitarysecretes oxytocin( )
Targeteffectors
Smooth musclein breast
Response Milk release
Pathway Example
Stimulus Hypothalamicneurohormonereleased inresponse toneural andhormonalsignals
Sensoryneuron
Hypothalamussecretes prolactin-releasinghormone ( )
Neurosecretorycell
Bloodvessel
Anteriorpituitarysecretesprolactin ( )Endocrine
cellBloodvessel
Targeteffectors
Response
Mammary glands
Milk production
(c) Simple neuroendocrine pathway
(b) Simple neurohormone pathway
(a) Simple endocrine pathway
Hypothalamus
Glycogenbreakdown,glucose releaseinto blood
Figure 45.2a–c
Figure 45.8-2
EXTRACELLULARFLUID
Hormone(estradiol)
Estradiol(estrogen)receptor Plasma
membrane
Hormone-receptorcomplex
NUCLEUS
DNA
CYTOPLASM
VitellogeninmRNA
for vitellogenin
Figure 45.7-2
Epinephrine
G proteinAdenylylcyclase
G protein-coupledreceptor
GTP
ATP
cAMP Secondmessenger
Inhibition ofglycogen synthesis
Promotion ofglycogen breakdown
Proteinkinase A
Figure 45.6-2
Lipid-solublehormone
SECRETORYCELL
Water-solublehormone
VIABLOOD
Signal receptor
TARGETCELL OR
Cytoplasmicresponse Gene
regulation
(a) (b)
Cytoplasmicresponse Gene
regulation
Signalreceptor
Transportprotein
NUCLEUS
Lipid-soluble (hydrophobic)Water-soluble (hydrophilic)Polypeptides Steroids
0.8 nmInsulin Cortisol
Amines
Epinephrine Thyroxine
3 Chemical classes of hormones
Because peptides are impermeable, they must use membrane receptors and second messenger signal transduction mechanisms to produce the desired effects.
Most use g-protein coupled receptors, but some use tyrosine kinase type receptors (i.e. insulin)
STIMULUS
HypothalamusReleasing Hormone
(Release-Inhibiting Hormone)
PituitaryStimulating HormoneGland
Hormone Target
Characteristics of hypothalamic releasing hormones
• Secretion in pulses• Act on specific membrane receptors• Transduce signals via second messengers• Stimulate release of stored pituitary hormones• Stimulate synthesis of pituitary hormones• Stimulates hyperplasia and hypertophy of target
cells• Regulates its own receptor
Hypothalamic releasing hormonesHypothalamic releasing hormone Effect on pituitary
Corticotropin releasing hormone (CRH)
Stimulates ACTH secretion
Thyrotropin releasing hormone (TRH)
Stimulates TSH and Prolactin secretion
Growth hormone releasing hormone (GHRH)
Stimulates GH secretion
Somatostatin Inhibits GH (and other hormone) secretion
Gonadotropin releasing hormone (GnRH) a.k.a LHRH
Stimulates LH and FSH secretion
Prolactin releasing hormone (PRH) Stimulates PRL secretion
Prolactin inhibiting hormone (dopamine)
Inhibits PRL secretion
Hypothalamus and Pituitary• The hypothalamus-pituitary unit is the most dominant portion
of the entire endocrine system.• The output of the hypothalamus-pituitary unit regulates the
function of the thyroid, adrenal and reproductive glands and also controls somatic growth, lactation, milk secretion and water metabolism.
Three major groups
1. Posterior pituitary/hypothalamus
• Vasopressin (ADH)
• Oxytocin
2. Anterior pituitary/hypothalamus
3. Catecholamines of the adrenal medulla
Tropic effects only:FSHLHTSHACTH
Nontropic effects only:ProlactinMSH
Nontropic and tropic effects:GH Hypothalamic
releasing andinhibitinghormones
Posteriorpituitary
Neurosecretorycells of thehypothalamus
Portal vessels
Endocrine cellsof the anteriorpituitaryPituitaryhormones
HORMONE FSH and LH TSH ACTH Prolactin MSH GH
TARGET Thyroid MelanocytesTestes orovaries
Adrenalcortex
Mammaryglands
Liver, bones,other tissues
Figure 45.16
Pinealgland
Cerebellum
Spinal cord
Cerebrum
Thalamus
Hypothalamus
Pituitarygland
Posteriorpituitary
Anteriorpituitary
Hypothalamus
Figure 45.14
• The posterior pituitary stores and secretes hormones that are made in the hypothalamus
• The anterior pituitary makes and releases hormones under regulation of the hypothalamus
2. Anterior pituitary –hypothalamus• Prolactin
• Thyroid stimulating hormone (TSH)
• Adrenocorticotropic hormone (ACTH)
• Growth hormone (GH)
• Follicle stimulating hormone (FSH)
• Leutinizing hormone (LH)
Most target other endocrine glands or cells
Example of Hormone Regulation – Vasopressin (ADH)
• Regulation of body water is a response to ECF volume changes (in particular, blood volume)
• When blood volume changes, volume receptors in the blood vessels and atria respond
• Carotid sinus and aortic baroreceptors
• Afferent nerves from these receptors go to the cardiovascular center in the brainstem
• Increased pressure would signal the center to
• Decreased pressure would signal the center to
• When blood volume changes, stretch receptors in the atria also respond
• Increased pressure also signals the cardiovascular center to
• Increased pressure signals the hypothalamus (this is where ADH release is controlled)
• When blood volume increases, filtration in the kidney is adjusted so that more fluid is filtered per minute
• Typically, under normal situations, the kidneys are not under the influence of ADH and water follows ions as they pass through the kidney tubules
• There are few aquaporin molecules in the cell membranes of the kidney collecting ducts in the absence of ADH. They are stored inside the cells.
Influence of ADH on the Collecting Ducts
Feedback Loop for ADH
Negative feedback
What regulates NaCl?
Regulation of Na+• Increasing osmolarity of the blood stimulates thirst behaviors, and increases
ADH secretion. Drinking and preventing water loss from the kidneys, decreases blood osmolarity
How would this graph change if an individual had hypertension (high blood pressure)?
Long-term regulation of Na+ • Under the control of aldosterone; it increases Na+ reabsorption into the
blood from the kidney filtrateWhat will happen to plasma [K+]?
What will be the overall effect on plasma osmolarity?
Oxytocin• Stimulates uterine contractions during childbirth by
mobilizing Ca2+ through a PIP2-Ca2+ second-messenger system
• Also triggers milk ejection (“letdown” reflex) in women producing milk
• Plays a role in sexual arousal and orgasm in males and females