Powerpoint Notes Flashcards
(136 cards)
1
Q
hormone
A
Hormones are chemical messengers synthesized by cells of endocrine glands or tissues, secreted into the bloodstream, and act on specific target tissues to evoke a specific physiological response.
2
Q
hormones are _____ in circulation and act on _____ target cells and tissue
A
transported
distant
3
Q
hormones affect _____ with highly ______ receptors which _____ and ______ with hormone
A
target cells
specific
recognize and bind
4
Q
Classic endocrine signaling
A
hormones are released into blood and lymphatic channels and circulate throughout the body to affect distant target cells
5
Q
Intracrine signaling
A
Synthesizing cell > Synthesizing cell
Signal affects within cells
non-classical local
6
Q
Neurocrine signaling
A
(or neural transmission or synaptic action)
Axon of presynaptic cell >Synapse > Postsynaptic target cell
non-endocrine signaling
7
Q
Exocrine signaling
A
cells secrete signaling molecules into into lumen of gut
8
Q
Ectocrine (pheromones)
A
One organism releases a substance causes a response in another organism
• Lee-Boot effect: Crowded female mice become anestrous when no males are present.
• Bruce effect: A newly mated female mouse will abort if placed with a strange male (not the previous mate)
• Dormitory effect: menstrual synchrony in all-females living groups
9
Q
Conclusion of Berthold’s experiment.
A
Presence of a testes is needed to maintain male behavioral and physiological functions.
10
Q
Male behavior: neural or hormonal regulation? (Berthold’s)
A
Hormonal – secretory, blood-born product of the testes determines rooster characteristics.
11
Q
Design an experiment to test your hypothesis.
(berthold, male hormonal behavior)
A
(1) Cut nerves of testes, roosters have normal appearance, development, and behavior – suggest NOT neural regulation. (2) Nerve re-connecting is nearly impossible.
Berthold’s follow-up experiment demonstrated that a testes-derived product exerts these effects in roosters:
Instead of replacing testes, replace extraction of testes.
Testes release an agent that may have direct effects or indirect effects
(activate a stimulatory effect/agent or remove an inhibitory effect/agent).
12
Q
compensatory hypertrophy
A
Hormones released from the testis (testosterone and inhibin) exert negative feedback on pituitary cells to restrain pituitary hormone release.
Lower than normal levels of testicular hormones stimulate the anterior pituitary hormone (FSH and LH) release, stimulate testicular growth and enlargement of the testis.
13
Q
what was bertholds (father of endocrinology) ultimate conclusion?
A
secretory, blood-borne product of the testes determines rooster characteristics.
14
Q
Conclusion of Starling and Bayliss’ experiment
A
Exp 1: Introduce acid into a denervated but vascularized section of the jejunum (part of small intestine) caused flow of pancreatic juice; which does not require nerves.
Exp 2: Introduce acid into an isolated piece of jejunum (part of small intestine).
Extracts of jejunum produced similar effects on pancreatic secretion.
15
Q
Pancreatic secretion (enzyme and HCO3-): neural or hormonal regulation? Explain. (Starling and Bayliss’)
A
Hormonal regulation. Nerve is not necessary.
A substance is liberated by the mucosa of the small intestine, gets into the blood, reaches the pancreas, stimulates the flow of pancreatic juice.
16
Q
Banting and Best’s experiment
A
isolated insulin reduced blood glucose levels in a diabetic dog, whose pancreas had been surgically removed. (discovered insulin)
Obtained extracts of pancreatic Islets => Insulin
17
Q
What did Otto Loewi demonstrate?
A
demonstrated neurons transmit using a chemical messenger in 1921
Vagus nerve releases substances (acetylcholine) causes relaxation of cardiac muscle contraction
18
Q
Conclusion of Loewi’s experiment
A
After stimulation, the vagus nerve releases acetylcholine on cardia muscle (also release into the media), which causes relaxation of cardiac muscle contraction.
19
Q
Heart rate (also cardiac muscle contraction): neural or hormonal regulation?
Explain.
A
Neurotransmitter – does not get into circulation.
20
Q
Claude Bernard stance on homeostasis
A
A constant internal environment is the condition of an independent life
21
Q
Walter Cannon
A
Coined the phrase “Homeostasis
22
Q
Compartments of body fluids
A
60% of body mass
Intracellular (2/3) and extracellular (1/3)
23
Q
how are intra and extracellular fluid similar
A
Both have: metabolic substrates and nutrients (sugar, fatty acids, amino acids), inoganic (electrolytes) and organic ions, metabolites, minerals, O2, CO2 .
24
Q
How are componnents of intra and extracellular fluids different
A
Extracellular fluid: extracellular matrix (proteins, polysaccarides, etc).
Intracellular fluid: proteins important in regulating cellular growth and metabolism, and cofactors (vitamins needed for enzyme function).
25
What are the two fluids that constitute the extracellular fluid? Are they same or different?
Interstitial fluid (75-80% of extracellular fluid) and plasma (20-25% of extracellular fluid).
Except for protein concentration is much higher in the plasma, two fluids are almost identical in composition.
26
What physiological variables need to be maintained in mammals?
1) Concentration of nutrients and waste products
2) Concentration of O2 and CO2
3) Concentration of salt and other electrolytes
4) pH of the internal environment
5) Volume and pressure of the internal fluid
6) Internal temperature
27
components of maintaining homeostasis
Variable, set point, inputs and outputs, receptors, effectors
28
Neg and Pos feedback stimulus (endocrine)
variable is out of the optimal range of set point.
For example: stimulatory factor causes an increase in secretion or
activity of a hormone on its target tissue.
29
Neg fdback endocrine responce
Effector target organ (secretion or metabolite) inhibitory control of hormone secretion
30
Pos fdback endocrine responce
stimulatory responce
31
Pos fdback endocrine results
maintain effects of stimulus factor explosive output events
32
Pos fdback endocrine significance
amplification of an endocrine signal; accelerates a process
33
Neg fdback endocrine results
Turn off effects of stimulatory factor (shuts the system off)
decrease in the magnitude of the stimulus
34
neg fdback significance
prevents from getting out of control
maintain at constant (baseline) level
maintain homeostasis
35
explain positive feedback in regards to
LH Surge and Ovulation
**Increased LH secretion stimulates estrogen production from the ovary which through positive feedback leads to the midcycle LH surge that causes ovulation**.(hypo and ant. pit.)
36
positive feedback (Parturition)
Oxytocin release is stimulated by neural inputs to the hypothalamus from cervical receptors during late pregnancy (dilation of the cervix), increasing uterine contractions.
A series of positive-feedback events involving neural and chemical cues promotes the cascade of uterine contractions (smooth muscle) during childbirth.
37
Feedforward regulation
anticipates a change
initiates an adaptive response before variable is being changed
happens before homeostasis has been disrupted
38
Feedforward regulation significance
speeds up homeostatic response
minimizes fluctuations, reduces the amount of deviation for the set point
39
example of One single gland that secretes multiple hormones
Presence of different types of endocrine cells in the same gland (testis: sertoli cells – inhibin, Leydig cells – testosterone; pancreas: insulin, glucagon, somatostatin; thyroid gland: thyroid hormones, calcitonin)
40
One hormone that is secreted by different organs
Somatostatin (from hypothalamic neurons regulates GH; from stomach epithelium regulates gastrin; from pancreas regulates insulin and glucagon)
41
One endocrine organ regulates another, which may then reciprocally regulate the first or regulate a third organ.
Hypothalamus-pituitary-gonads/thyroid/adrenal cortex/liver/breasts
Angiotensin (liver) – aldosterone (adrenal cortex) – kidney tubule
Parathormone (parathyroid) – Vit D (kidney) – intestine
42
types of peptide horomones
insulin, gastrin, vasopressin,
growth hormone, prolactin,
many hypothalamic releasing hormones
43
peptide horomone biochemistry
short chains of linked amino acids
## Footnote
Amino end (NH2) = N-terminal group;
Carboxy end (COOH) = C-terminal group
44
\*1st step of insulin\*
how does Modification of preproinsulin into mature insulin occur
via processing through the secretory pathway
45
The conversion of the nascent preproinsulin molecule into proinsulin in the RER (rough ER) is accompanied by....
removal of the signal peptide and formation of disulfide bonds.
46
After sorting through the Golgi is completed, proinsulin is converted to **insulin** within .....
the immature secretory vesicles through the actions of the prohormone **convertases** (Any of several enzymes that convert a compound into smaller, biologically-active compounds).
47
\*final insulin step\*
## Footnote
Mature insulin is then retained in the \_\_\_\_\_\_\_\_\_\_\_, and is eventually stored within the \_\_\_\_\_\_\_\_\_\_\_\_. Both insulin and the inactive C chain peptide are released via \_\_\_\_\_\_\_\_.
immature secretory granule
mature secretory granule
48
Amines
amino acid-derived hormones
49
Catecholamines
- Derivatives of amino acid tyrosine
- INCLUDE: Dopamine (hypothalamus); epinephrine and norepinephrine (adrenal medulla)
- Water-soluble (hydrophilic)
50
Thyroid hormones
INCLUDE: Thyroxine and Triiodothyronine
- Derivatives of amino acid tyrosine
- Unique since inorganic iodine ion is incorporated into structure
- Lipid-soluble (lipophilic)
51
Indolamines (hormone melatonin)
- Derivatives of amino acid tryptophan
- Precursor to melatonin is serotonin (a neurotransmitter derived from the amino acid tryptophan; is water-soluble)
- Synthesis and secretion of melatonin from the pineal gland is affected by light exposure to the eyes
- Lipid-soluble
- Membrane receptor
- Amine
52
Steroid Hormones
**- Lipid-derived hormones**
## Footnote
- Derived from cholesterol
- Gonadal or adrenal cortex origin,
includes **Adrenal cortex** – corticoid hormones
Glucocorticoids e.g. cortisol
Mineralocorticoids e.g. aldosterone
**Kidney** - 1,25-dihydroxyvitamin D (Ca2+ balance)
**Gonads** -
Progestin steroid hormones (e.g progesterone, pregnenolone)
Androgen steroid hormones (e.g. testosterone, 5-DHT)
Estrogen steroid hormones (e.g. 17β-estradiol, estrone)
53
Progestin steroid hormones
progesterone, pregnenolone
54
Androgen steroid hormones
testosterone, 5-DHT
55
Estrogen steroid hormones
17β-estradiol, estrone
56
what kind of horomone are Eicosanoids
lipid-derived
57
Eicosanoids
Generally function as **paracrine** signals
* Coupled to endocrine signals by stimulating synthesis of hormones (such as testosterone and corticosteroids)
* **Diverse** functions: blood clotting (prostacyclins and thromboxanes), induction of inflammation and fever (prostaglandins and leukotrienes), smooth muscle contraction, vasodilation, vasoconstriction, and bone remodeling (prostaglandins)
* Increase **inflammation**, regulate **immunity** (leukocytes recruitment, cytokine production, antibody formation, cell differentiation, cell proliferation, migration and antigen presentation)
58
Arachidonic acid
a polyunsaturated fatty acid present in the phospholipids of membranes of the body's cells, and is abundant in the brain, muscles, and liver.
lipid-derived horomones derived from them
59
Aspirin-like drugs suppress inflammation by \_\_\_\_\_\_\_\_
inhibiting prostaglandin (an eicosanoid) synthesis.
60
Endocannabinoids
- signaling molecules
- Two most biologically active endocannibanoids are anandamide and 2-arachidonoylglycerol (2-AG).
–neuromodulatory lipids produced by the brain (fatty acid neurotransmitters)
–Chemically similar to cannabinoids (Δ9-tetrahydrocannabinol THC and cannabidiol CBD) found in cannabis plant (such as Marijuana)
• stimulate appetite, pain-sensation, immune response, blood pressure, stress, mood, memory, sleep, and thermoregulation.
61
Peptide hormones - solubility?
- Water-soluble (hydrophilic)
- Do not passively permeate cells by diffusion through plasma membrane
- typically interact with cell surface membrane receptors, then coupled to activation of intracellular signal transduction pathways
62
Amines/ thyroid horomone solubility
- Lipid-soluble (lipophilic)
- Typically interact with a cytosolic or nuclear receptor
63
Amine/Catecholamines solubility
- Water-soluble (hydrophilic)
- typically interact with cell surface membrane receptors
64
amine/Indolamines specifically serotonin solubility
- Water-soluble neurotransmitter
- packaged into vesicles prior to export
65
amine / Melatonin solubility
- Lipid-soluble (high lipid solubility; low water solubility)
- Leaves pineal gland via passive diffusion
- Binds to cell surface membrane receptors
66
Peptide hormones synthesis
Typical protein synthesis - synthesized as preprohormones; prohormones (ER)
Initial events occur within the secretory cell – convert large gene products to smaller secretory forms.
Once secreted, a peptide encounter peptidases which inactivate the peptide or convert it to forms with different biological activities.
67
how can Hormone isoforms arise?
from differential splicing of mRNA (separate gene products) or post-transcriptional or post-translational modifications (sulfation, glycosylation, etc.)
68
POMC
ex of multiple horomones being produced from one gene transcript
## Footnote
Depending on what pituitary cell type expresses it, can be converted different active hormones
69
amines / Thyroid hormones synthesis
Synthesized on large proteinaceous substrate in lumen of thyroid
Synthesized on thyroglobulin (large proteinaceous substrate) in lumen of thyroid
70
lipid derived / Steroid hormones synthesis
Synthesis occurs in smooth ER and lipid-rich cells of gonads and adrenal gland
Requires numerous complex, multi-enzyme synthetic pathways (both cytoplasmic and mitochondrial)
71
Steroid hormone synthesis from cholesterol
Following import cholesterol into mitochondria via transmembrane steroidogenic acute regulatory (StAR) transporters, cholesterol is converted into pregnenolone.
Pregnenolone is converted to progesterone in the smooth ER. The smooth ER of sex steroid producing tissues, such as the testes and ovaries, convert progesterone into sex steroids, which diffuse into the blood stream. Corticosteroids, such as aldosterone and cortisol, require further processing by the mitochondria prior to release by adrenal cortex cells.
72
synthesis of sex steroids
Pregnenolone is converted to progesterone in the smooth ER. The smooth ER of sex steroid producing tissues, such as the testes and ovaries, convert progesterone into sex steroids, which diffuse into the blood stream. Corticosteroids, such as aldosterone and cortisol, require further processing by the mitochondria prior to release by adrenal cortex cells.
73
Eicosanoid hormone biosynthesis pathways
Arachidonic acid is synthesized by the action of phospholipase A2 (PLA2) on smooth ER membrane phospholipids.
Lipoxygenases convert arachidonic acid into leukotrienes, and cyclooxygenases use arachidonic acid to generate prostaglandins, thromboxanes, and prostacyclins.
Whereas anti-inflammatory steroids inhibit the synthesis of all eicosanoids by inhibiting PLA2 activity, non-steroidal anti-inflammatory drugs (NSAIDS) specifically inhibit the synthesis of eicosanid products generated by COX enzymes.
74
endocannabinoids synthesis (lipid derived)
by cleavage of phospholipid precursors that are present in cellular membranes
75
C-peptide
a short chain of amino acids that is released into the blood as a byproduct of the formation of insulin by the pancreas.
76
When insulin is released from the beta cells into the blood in response to increased levels of glucose, equal amounts of _____ are also released.
c-peptide
77
Peptide hormone secretion
Packaged into secretory vesicles; released by exocytosis
Prohormones can be secreted & altered after secretion
78
Insulin is degraded in the _____ after secretion which occurs pretty fast
liver.
c-peptide an indicate insulin level
79
Secretion is regulated by
hormonal and neural factors.
80
Regulated release secretion (peptide horomone) occurs when
Ca2+ enters stimulated cells
81
Calcium dependent exocytosis - requires increase in
[Ca2+]
82
Amines / Thyroid hormones secretion
Constitutive release secretion – minimal storage; dependent on rate of synthesis
Synthesis is regulated by synthetic enzyme activities.
83
Catecholamines secretion
Regulated release secretion
84
Serotonin secretion
Regulated release secretion
85
Melatonin secretion
Constitutive release secretion
86
Constitutive release secretion
minimal storage; dependent on rate of synthesis
87
Regulated release secretion
occurs when Ca2+ enters stimulated cells
88
Steroid hormones and endocannabinoids secretion
Constitutive release secretion – minimal storage; dependent on rate of synthesis
89
Insulin input signal
increase in plasma glucose
90
Glucagon input signal
decrease in plasma glucose
91
Parathyroid hormone input signal
decrease in plasma calcium
92
Calcitonin input signal
increase in plasma calcium
93
Growth hormone input signal
increase in plasma amino acids
94
Example of hormone(s) secreted;
only during special circumstance (e.g. pregnancy)
human chorionic gonadotropin (hCG)
95
Example of hormone(s) secreted;
## Footnote
response to specific stimulation (e.g. suckling)
oxytocin
96
Example of hormone(s) secreted:
in a pulsatile pattern
gonadotropin-releasing hormone (GnRH)
97
Example of hormone(s) secreted:
with a circadian rhythmicity
cortisol
98
Example of hormone(s) secreted:
response to stress
adrenal catecholamines/adrenal steroids
99
Example of hormone(s) secreted:
at higher levels during pubertal maturation
gonadotropic hormones (FSH & LH) / gonadal hormones / growth hormone
100
Functions of hormone binding globulins:
1. Globulins transport hormones
• increasing solubility of hormones in blood
2. Regulate bioavailability of hormones
• since bound hormone cannot enter cells and have physiological action
3. Regulate metabolic clearance of hormones
• since bound hormone can not enter liver/kidney cells for degradation and excretion
4. Storage of hormone
* provide readily available store of hormone
* carrier proteins extend the half-life of a hormone
101
peptide circulation
free unbound
102
amine thyroid circulation
Bound to carrier proteins (binding globulin)
103
amine catecholamines circulation
free unbound
104
amine Melatonin circulation. bound how?
~ 70-80% Bound to carrier proteins;
~ 20-30% free
105
Steroid hormones circulation
- Bound to carrier proteins in blood circulation (globulins)
- Examples:
* corticosterone binding globulin (CBG)
* steroid hormone binding globulin (SHBG)
106
Endocannabinoids circulaion
- Bound to fatty acid biding proteins
107
T1/2 half-life
Amount of time required for half the molecules to become inactivated or cleared from the circulation.
108
Peptide hormones metabolism
- Short T1/2
- Inactivated by enzymes
- Liver and/or kidney and/or target organ Internalization
109
Thyroid hormones metabolism
- Bound to protein carrier - longer half-life
- Occurs in many tissues, usually by deamination
- Deiodinating enzymes (modify T3/T4 hormones)
- In liver, conjugation to glucuronic acid occurs à bile salts (Fig 2.9)
110
Catecholamines metabolism
- In liver and brain
- catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO)
111
Melatonin metabolism
- In liver by melatonin hydroxylase
- Then convert to a sulfate or a glucuronide for urinary excretion
112
Steroid hormones metabolism
- Bound to protein carrier - longer half-life (except aldosterone)
- Metabolism typically occurs in liver
- Convert to steroid sulphates and steroid glucuronides (make them water soluble for excretion in urine) (Fig 2.9)
- May be excreted with bile salts (from the bowel)
113
Peptide hormones Action Mechanisms
- bind to surface receptors on target cells
114
Thyroid hormones Action Mechanisms
bind to nuclear receptors of target cells
115
Catecholamines action mechanisms
- bind to surface receptors
116
steroid horomone action mechanisms
bind to intracellular receptors
117
Endocannabinoids action mechanisms
- bind to surface receptors
118
Lipid soluble hormones action mechanisms (steroid and thyroid hormones)
easily pass through cell membrane, bind to cytosolic and nuclear receptors in order to regulate gene expression.
119
**GnRH**
a. Major structural class of hormone
Solubility:
b. Synthesis
c. Secretion into portal vessel blood
d. Circulation
e. Metabolism
f. Action mechanisms
a. Major structural class of hormone
Peptide hormone;
Solubility – water soluble
b. Synthesis
precursor: preproGnRH
encoded by a gene
process: ribosomes – DNA à mRNA à preproGnRH
Golgi (proteolytic processing enzymes) – cleave to proGnRH and mature GnRH
c. Secretion into portal vessel blood
regulated release mechanism (in pulsatile release pattern)
d. Circulation
not bound to a carrier in blood (free form)
e. Metabolism
short half-life in blood; metabolized by peptidases, at the liver, kidney and target organ
f. Action mechanisms
membrane receptors
120
**Estrogen**
a. Major structural class of hormone
Solubility:
b. Synthesis
c. Secretion into portal vessel blood
d. Circulation
e. Metabolism
f. Action mechanisms
a. Major structural class of hormone
Steroid hormone
Solubility – lipid soluble
b. Synthesis
precursor: cholesterol;
process: LH binds to G-protein coupled receptor on ovarian thecal cells; via 2nd messenger system, activates cholesterol esterase, which frees cholesterol from lipid droplets; mitochondria, smooth ER and cytoplasm – Sequential modifications of cholesterol by steroidogenic enzymes
c. Secretion into circulation
Constitutive release secretion – depends on synthesis rate, which is regulated by feedback mechanism
d. Circulation
bound to a carrier in blood (SHBG)
e. Metabolism
long half-life in blood, metabolized in the liver and kidney
f. Action mechanisms
Mainly nuclear receptors
121
**Dopamine**
a. Major structural class of hormone
Solubility
b. Synthesis
c. Secretion into portal vessel blood
d. Circulation
e. Metabolism
f. Action mechanisms
a. Major structural class of hormone Amines (Catecholamines)
Solubility – water soluble
b. Synthesis
**precursor**: tyrosine
**process**: Tyrosine à L-DOPA (by tyrosine hydroxylase) à dopamine (by DOPA decarboxylase)
c. Secretion into portal vessel blood
* regulated release mechanism*
d. Circulation
* not bound to a carrier in blood*
e. Metabolism
* short half-life in blood; metabolized in the liver or the CNS by enzymes COMT and MAO*
f. Action mechanisms
* membrane receptors*
122
Neuroregulators
include neurohoromones, neurotransmitters, neuromodulators.
usually synthesized in neurons
123
Neurohormones
- Synthesized and released by neural cells à circulation
- Nonpeptidergic (dopamine) or peptidergic, these are generally hydrophilic
Synthesis - Remember preprohormone and prohormone forms for peptidergic.
Synthesis can also be enzymatically converted from tyrosine
124
Neurotransmitters
- Synthesized in neurons and released into synapses;
- Peptides (i.e., substance P) or non-peptides (acetylcholine, histamine, serotonin, etc.)
125
Neuromodulators
- Synthesized in neural and non-neural tissues
- Modulate neural function
- Longer lasting, slower effects
126
Cooperative activity of AMPA and NMDA receptors essential for
long-term potentiation
127
Eicosanoids (prostaglandins etc.)
- Produced by all tissues from membrane arachidonic acid
- Work in a paracrine or autocrine manner
- Rapidly degraded in lung
- Eicosanoid hormones are generally lipophilic, but work by binding to cell surface receptors
128
Pheromones - Intraspecific (within species) chemical messengers.
They differ from hormones by:
They are transmitted via the external environment.
They have a higher degree of species specificity.
They produce adjustments in the bodies of other individuals.
129
Hyposecretion
too little horomone
130
Primary Hyposecretion
gland destruction
decreased hormone synthesis
dietary deficiency (iodine)
131
Secondary Hyposecretion
too little tropic hormone
132
Addison’s disease
failure to secrete cortisol due to adrenal cortex tuberculosis
failure to secrete ACTH from pituitary gland or CRH from hypothalamus
133
Hypersecretion
overproduction of hormone secretion
134
Primary Hypersecretion
overproduction of hormone secretion
135
secondary Hypersecretion
excessive stimulation by tropic hormone
136
Cushing’s syndrome
excess cortisol secretion due to adrenal cortical tumors
excess ACTH from pituitary gland or CRH from hypothalamus
