1
Q
Behavioral Endocrinology
A
the study of the interaction between hormones and behavior
- behavioral endocrinologists use a variety of techniques and are represented in many fields
2
Q
Aristotle
A
he thought that if you damaged the area near a bird’s genitals, that is loses male traits
- it’s cromb turns pale, it stops crowing, and loses sexual desire
- if this happens when the bird is young, it never develops male traits at all
**Aristotle thinks this also applies to humans
3
Q
Charles Edouard Brown-Sequard
A
he furthered mainstream scientific interest in internal secretions with his famous auto-experimentation
- he studied the anatomy and physiology of the spinal cord
- he was the first scientist to work out the physiology of the spinal cord, demonstrating decussating (***he found it crosses like an X) of the fibers carrying pain and temperature sensation occurs in the cord itself
4
Q
Brown-Sequard Syndrome
A
when you cut the spinal cord in half vertically, this results in paralysis and loss of proprioception (sense location, movement, and actions) on the same (ipsilateral) side as the injury or lesion (area of body that’s been damaged) and loss of pain and temperature sensation on the opposite (or contralateral) side as the lesion
**contralateral –> pain and temperature
**ipsilateral –> proprioception
5
Q
Brown-Sequard (1817-1894)
A
- he was one of the first people to believe the existence of substances (hormones) secreted into the bloodstream to affect distant organs
***there is something in peripheral tissues that you can extract, inject, and use to impact behavior
- Sequard reported that he had rejuvenated himself, increased his physical strength, mental abilities, and appetite by injecting himself with an extract derived from the testicles of dogs and guinea pigs
*he claimed that the daily injections made him feel younger
- he could lift heavier weights than before, work for hours after dinner, and run up and down steps (this caused others to research organotherapy (using animal tissues or extracts to rejuvenate human organs)
6
Q
Testosterone Production in Men
A
as males age, hormones change
- companies promote the idea of HRT for the purpose of growing tissue and increasing strength
testosterone production in men increases when they get 20 and then starts decreasing when they get older than that
US Hormone Replacement Therapy Market:
- it keeps increasing over the years in billions (starts in 2020 at 7.2 Billion)
products:
- DHEA supplement (increases estrogen and tesosterone)
- Androgel (prescription medication used for hormone replacement therapy in adult males with low or no testosterone)
7
Q
Arnold A. Berthold
A
he was the first person to recognize experiments in behavioral endocrinology
- he did a series of tests on roosters in 1849 while he was curator of the local zoo
- he’s famous for a study he did on roosters and their testes
8
Q
Rooster and Hen
A
comb = the top of the hair of the rooster
wattle = the bottom red part of the rooster’s mouth
9
Q
Berthold’s Rooster and Chickens
A
experiment:
He put 6 cockerels (young chickens) into 3 experimental groups, each with 2 birds
- He removed the testes from each of the two cockerals in the first group, and they developed as capons (immature adult chickens) – they showed their weird behavior, and their bodies were different (small head and body, and their combs and wattles were atrophied and pale in color)
The second pair of cockerals (group 2) were also castrated but he reimplanted one testis from each bird in its stomach — these birds grew up exactly like roosters, looked like them and acted like them
The last group were castrated, but after their testes were removed, he testes from different birds in the other’s stomach — they also developed normally like roosters
- He studied the testis he implanted and they connected to the body’s system and produced sperm
10
Q
Berthold’s Experiment - Conclusions
A
**the testes were transplantable organs
- Transplanted testes function and produce sperm
No specific nerves telling testicular function what to do because he cut the original nerves
when he castrated the chickens
***he decided that there must be something secreted in the blood
***he found that testes influence behavior not by the action of nerves, but by secreting a substance into the bloodstream
11
Q
Berthold’s Experiment Summary
A
Group 1: castration
caponization
- small comb and wattles
- no interest in hens
- no aggression toward other males
group 2: castration and reimplantation of testes
*normal male development
- normal comb and wattles
- normal male behavior
group 3: castration and transplantation of testis
*normal male development
- normal comb and wattles
- normal male behavior
12
Q
Berthold Forward Thinking
A
Berthold proposed that a secretary blood-borne product of the testes was responsible for normal development
- these substances travel thru the bloodstream to target organs
13
Q
Lead Exposure Risk and Family Income
A
there’s an association of lead-exposure risk and family income with childhood brain outcomes
***exposure to heavy metals impacts cognitive function –> poorer cognitive performance
high income: higher cognitive test scores and higher
middle income: middle cognitive test scores
low income: lowest cognitive test scores
***more lead exposure causes less cortical volume
14
Q
Hormones
A
organic messengers made and released by endocrine glands
- can act over a long distance
- coordinate phsyiology and behavior and reproduction
***hormones can also act as neurotransmitters
**long distance, slower acting (because they travel), graded response (more hormones, more response)
graded response = gradually you get more hormones and more response
15
Q
Neurotransmitters
A
chemical messangers used by the nervous system
- they travel short distances
- some neurotransmitters can act as hormones
- acts across the neural synapse
- short distance, fast acting, sort of digital response (when it hits a receptor, something will happen)
16
Q
Cytokines
A
chemical signals made by cells of the immune system
- cytokines are important in health and disease and are important for healthy immune system function
**they can travel locally or through the bloodstream
- locally = they don’t travel thru the bloodtsream and instead, acts once it’s released on nearby cells
17
Q
Presynaptic Neuron
A
the whole presynaptic neuron = axon terminal
- there’s synaptic vesicles
- voltage-gated Ca+++ channels
18
Q
Postsynaptic Neuron
A
*the synaptic cleft is between the presynaptic neuron and the postsynaptic neuron (short distance)
- there;s neurotransmitter receptors at the top of it
- the bottom part is the dendrite spine
19
Q
Neural Transmission (synaptic cleft)
A
- controlled
- fast
- digital response, happens or not
- eating movement
20
Q
Hormonal Communication
A
- bloodstream
- somewhat not controlled
- slow
- analog (graded response)
- growth
21
Q
Hormones Influence Behavior
A
birds singing example
*** Hormones increase the probability of things happening
**behavior also influences hormones
22
Q
Singing in Birds
A
Singing in Birds:
- Only male zebra finches sing
- If the testes of an adult male finches are removed, then the birds reduce signing, but castrated finches resume singing if the testes are reimplanted or if the birds are given testosterone or estrogen
Singing behavior is most frequent when blood estrogen concentrations are high
normal bird: song
castrated bird: no song
bird with testosterone replacement: song
***hormones increase the probability of things happening
23
Q
2010 World Cup Soccer
A
*behavior influences hormones
watching the final world cup soccer game
***increased testosterone in males, but not females
24
Q
Evidence for Determining Hormone-Behavior Interactions
A
- the behavior should disappear when a source of hormones are removed or actions of hormones are blocked
- after the behavior stops, restoration of the hormone should reinstate the behavior
- Hormone concentrations and the behavior they want should be covariant (should be related - they have a relationship)
- this is complicated
25
Ablation and Replacement
*Berthold's Experiments
goal: determine if the gland is responsible
***tests if hormone influences Behavior
4 steps:
1. castrated
- the gland that is suspected to be the source of the hormone affecting behavior is removed
2. the effects of the removal are observed
3. hormone are restored (by gland or injection)
- Berthold did restoration by reimplanting testes onto the bird that was castrated before
4. determine if consequences of ablation (removing tissues) can be reversed
26
Radioimmunoassay (RIA)
***measures levels of hormones within a sample
*many techniques are immune-related
***Rosalyn Sussman Yalow discovered this technique
- she used radioactivity to measure activity
antibody (against oxytocin) binds to the specific target/antigen (oxytocin)
27
RIA Specifics
uses radioisotopes to detect antigens and antibodies within that sample
- competitive binding between the radioactive labeled antigen and the unlabeled one
an antibody produced because of an antigen (or hormone) has a binding site for a specific antigen
- antibody has certain number of binding sites for its antigen
**an antibody doesn't know the diff. between an antigen that is radiolabeled or a normal nonradiolabeled antigen
- the radiolabeled and the non-radiolabeled hormone compete for binding sites on the antibody so the non-radiolabeled hormone is in the tube and the other will bind to the antibody
***measure the radioactivity from the radiolabeled hormone to determine how much of the radiolabeled hormone you have
28
Comparing RIA sample
the patient sample has unknown amount of substance (ex: oxytocin)
- you compare the radioactive (labeled) and the non-radioactive (non-labeled) and see which bonded to more antibodies
***if there is more antigen (non-labeled oxytocin) binded to the antibodies, then less radioactive antigen is able to bind, so there's lower levels of radioactive antigens
rule: if high amount of non-labeled antigen, there's low radioactivity
29
RIA Steps
prepare the sample and dilute it
- make the antigen radioactive and then label it
- then put the antibody into the well and let it incubate
- then antigen competition happens (compete for binding sites on the antibody)
- the radioactivity of the wells is measured using gamma counter
- if there's more unlabeled antigen = decreased radioactivity
ex: if the sample has a lot of norepinephrine, that means the enzyme makes a lot of radioactive product
***if a lot of the hormone is in the blood, that means the unlabeled antigen binds more to the antibody which means there's less radioactive antigen (if you see less radioactivity (less binding of radioactive antigen) you can conclude that there's higher levels of that hormone in the body)
- you don't know unlabeled antigen amount, but you do know radioactive (labeled) antigen amount
ex: using RIA to measure insulin in the blood
30
Example of RIA using Oxytocin
get hormone labeled/unlabeled
- put the labeled one in well plate -- the antibodies bind to plate (ex: anti oxytocin)
**you saturate the plate with radioactive oxytocin
2. put a known amount of unlabeled oxytocin and measure how much labeled oxytocin is kicked off (over time, more unlabeled oxytocin might get kicked off)
3. pour in the rat blood to determine the concentration
- plot the concentration curve using known amounts (standards)
- test the unknown one and plot it
31
Enzyme Immunoassay - Overview
EIAs (or ELISA) are used to measure levels of hormones using enzyme reaction
- they use antibodies and color changing enzymes to tell you if you have positive or negative test results
(3 types: direct, indirect, and sandwhich)
32
Steps of EIA
1. binding/blocking
- the primary antibody binds
- it gets attached with a blocking agent
step 3: sample added
- if the antigen/hormone/protein is present, then it will bind to the primary antibody
step 4: washing
- the unbound antigens get washed away
- either tris or phosphate-buffered saline
- the antigens that are bound stay there
step 5 and 6: secondary antibody/washing
- the secondary antibody and the enzyme get added (if the secondary antibody is not enzyme-conjugated (means the hormone is bound to the antibody), a third antibody can be used)
- then wash again
step 7: substrate added
- enzyme then coverts the substrate to a colored product
step 8: color change
- if there's a color change then, it's positive
- if there's no color change, then it's negative
33
Example of EIA: Pregnancy Test
first the antibody is present
- if hCG is present, then it binds to first anti-hCG antibody
test region:
- the anti-hCG antibodies (they can't move) make a sandwhich
- there's a color change from the enzymes
- the color change in this region (second line) tells us that hCG is present
***unbound antibodies move to control region
- they bind to third type of antibody
- the attached enzyme causes a color change
- color change in this control region means the test is working correctly
34
Human Chorionic Gonadotropin Hormone
this is the pregnancy hormone (only pregnant ppl have it)
*HCG made by the placenta during pregnancy
- an egg is normally fertilized by a sperm cell in a fallopian tube
- after 9 days, the fertilized egg moves down the fallopian tube into the uterus
- the blasocyst then implants itself to the wall of the uterus
35
HCG - Blastocyst Stages
blastocyst attaches (implants) itself into the wall of the uterus
the outer layer of the blastocyst becomes the trophoblast
- forms the outer layer of the placenta
- the growing placenta starts releasing hCG into your blood
summary: blastocyst --> trophoblast --> placenta --> hCG
**we can tell if someone is pregnant by detecting hCG
36
Days of the fertilized egg
ovulation
- oocyte
fertilized egg (zygote)
day 1: first cleavage
day 2: 2 cell-stage
day 3-4: 4-cell stage
- 8 cell uncompacted morula
day 4: early blastocyst
day 8-9: blastocyst implants
37
hCG Mouse
the anti hCG from the mouse gets put onto a test
- then it binds to the HCG
- the one line is test line
- then anti mouse (the unbound antibodies and the imbolized antibodies) recognizes it and binds to the antibodies on the reaction zone (2 lines)
38
Negative Pregnancy Test
the antibodies aren't bound to hCG
- they don't bind to anti-hCG
- they bind to the control --> dye changes color
39
EIA vs. RIA
EIA:
- uses color change
- less sensitive
- consumer friendly (can do at-home tests)
RIA:
- uses radioactive isotopes
- more sensitive
- used in lab setting
40
Immunocytochemistry
measure protein (receptors) levels
there is direct and indirect immunocytochemistry methods
***good for cell counting
***better at looking at location of receptors
*both use antibodies with fluorescent tags as a way to measure the location and abundance of proteins within cells
steps: pick the protein recpetor (ex: serotonin receptor)
- then stain it with a florescent tag
- then add the antibody that matches the protein or hormone they're looking for (the antibody then sticks to the protein/hormone inside the cell wall)
- then they add the second antibody which then sticks to the first antibody (the second one has the dye)
- look under microscope to see where the location of receptors are
41
Immunocytochemistry - DIRECT
direct: *the antibody is labeled with a viewable dye (ONLY 1 ANTIBODY = PRIMARY)
- one antibody (primary) is linked directly to a fluorescent molecule
- weaker signal if there's a low amount of protein
- quicker and cheaper
**use direct immunochemistry when you want a result fast and don't want to do a lot of background staining and there's a lot of antigen
42
Immunocytochemistry - INDIRECT
uses 2 antibodies (an unlabeled primary one to bind to the protein and an secondary one to detect where the protein is)
- primary antibody binds to the target protein, and then the secondary antibody (with florescent tag) binds to the primary antibody
**called indirect ICC because the color comes from the secondary, not the primary
- it's sensitive so it detects small amount of proteins
- strong, bright signal
- takes longer, more background staining (showing color where there shouldn't be)
- do blocking to fix extra background staining
43
Immunosytochemistry - Estradiol example
pregestin receptor expression within hypothalamus
estradiol-treated: *a big increase in receptors with the Estradiol-treatment
***subjects who were treated with estradiol had an increase in progesteron recpetors than subjects who weren't treated with estradiol
oil treated: way fewer receptors (barely any)
**estrogen increases progestin receptors
44
Western Immunoblot
*measures protein (recepetors) levels
- good at measuring the amount of receptors
- more quantitative
*separates proteins by their size
steps:
clumped cells
then they homogenize (they break up the cells to release a protein) the cells with a detergent
then it adds a negative charge to proteins by treating it with SDS (sodium dodecyl sulfate)
all of this is loaded into the gel:
- the mixture of proteins goes into the gel electrophoresis with a negative charge at top
- then the large molecules stay at the top of the well (negative) and the small molecules migrate to the bottom (positive end)
**negative proteins move to positive side
45
Western Blot goal
western blot happens to get immunocytochemistry (the whole point)
**better at quantifying the receptors
*the molecules from the well transfer to the membrane (filter) = blotting
- you incubate the membrane with the antibody against the protein you want
- then the primary antibody binds to a specific protein band
- then the secondary antibody with dye binds to make the protein band visible
- then you can detect the bound antibody by chemiluminescence (looks like bands)
(the reaction makes bands that you can see so you can detect the target proteins)
***if you can see the band, that means that there's a protein and it tells you the size of the protein
46
In Situ Autoradiography
*measures hormone binding -- way to visualize how much hormone is being used by looking at if they binded or not
- a method used to determine where a hormone is binding in the brain
- attach a radioactive probe in the brain
- ligand (molecule) (ex: estrogen) gets labeled with radioactivity
- then it gets spread onto slide
- the receptors in the brain where hormones bind to cells
steps:
- put radioactively tagged hormones to a sample
- Hormones bind to their receptors
- Using a tool to detect radio active emissions, you can see where the hormones bound to their respective receptor
- Radio = radioactive + Graphy = image
**you see where the dark spots on the film are and the spots correspond to the locations in the brain tissue
47
Why use In Situ Hybridization
the location is important for where the gene expression is
- it can show you if what you're looking for is there and where it is
ex: diagnosing cancer -- shows you if there's cancer and where it is
48
In Situ Hybridization
*measures RNA levels and where it is in the tissue
- if you know the structure, you can use this technique
*you want to look at RNA (not DNA) because RNA is single-standed and once you have RNA, you can get the protein
hybridization = base pair binding between complemenatry sequences
nucleus:
- DNA replication happens
- transcription
- then RNA and then RNA
- translation then forms protein
*if you know DNA, then you know RNA, which is targeted by the in situ hybridization
in situ hybridization targets RNA to see where it is in the cell
- uses a labeled probe with a complementary DNA sequence to the RNA that they're looking for (the labeled prob on the DNA sequence will attach to the RNA)
- the labeled probe binds to the RNA (hybridizes)
49
Transgenic
*genetic manipulation -- it asses the function
***test the consequence of deleting or altering the expression of a gene (removes receptors/proteins) by the mutant to study gene function
50
Optogenetics - Halorhodpsin
**genetic manipulation -- assesses function
***virus/gene manipulation technique to turn off or on particular cells or brain regions
*uses light to turn cells off or on
*shining light on part of their brain to open channels and then observe behavior
- the halorhodpsin is a light-gated ion pump, which only chloride ions can go thru
*injected via viral vector
- action potentials on both ends
yellow light gets emmited outside the cell and the NpHR receptor then allows the Cl- to go through the cell
**more negative hyperpolarization of the cell
51
Optogenetics - Channel rhodopsin
it's also a light activated channel pump but only for Na+
*injected via viral vector
(470 nm of light)
- action potentials in the middle
blue light gets emmited from the outside of the cell, and then ChR2 receptor allows the Na+ to go thru the channel
*more positive depolarization in cell
52
Optogenetics Steps
illumination cqauses the inhibition or activation of action potentials
then through the cortex, there's optical stimulation
- targeted neuron type expressing ChR2 or NpHR
- the adjacent non-targeted neuron (unaffected)
problem:
- it's hard to get light into the brain
- you can see where/broad regions, but not change expression or target genes that are being affected
- it's invasive - you have to put a probe into their brain
53
Chemical Messenger
any substance that is made by a cell that effects the function of another cell
ex: a hormone
54
Neuromodulator
a hormone that changes (modulates) the response of a neuron to some other factors
ex: botox -- temporarily relaxes muscles reduce wrinkles
55
Neurohormone
a hormone produced by a neuron
ex: oxytocin and vasopressin
56
Neuropeptide
a peptide hormone made by a neuron
ex: oxytocin
57
Neurosteroid
a steroid hormone made by a neuron
ex: progesterone
58
Intracrine Mediation
- no secretion
- produced in cells, regulates intracellular events
(we can assume it's hormones or a signaling molecule)
mechanism where things are made in the cell and act directly on the parts inside the cell (like the nucleus)
***a hormone can be intacrine, autocrine, and paracrine all at once
59
Endocrine Mediation
- secretes chemicals into the bloodstream
- influences distant target cells
ex: the hormone gets secreted into the bloodstream and then acts on distant target cells
60
Autocrine Mediation
- produced in cells, secreted locally (it means the hormone or substance gets secreted and immediately acts on nearby cells - doesn't get transport thru the bloodstream)
- influences the same cell that secreted it
61
Paracrine Mediation
affects adjacent cells
- local signaling
62
Ectocrine Mediation
released into the environment by individuals to communicate with others
ex: pheremones, defensive toxins
63
Endocrine Cells
****they secrete hormones into the bloodstream
- the secretory vesicle blips off and secretes the hormone thru the cell membrane and into the bloodstream
- once in the bloodstream it binds to hormone receptors on the target cell
64
Exocrine Cells
***they make chemicals and then secrete them via ducts into the epithelium (tissue) -- doesn't go directly into the bloodstream
ex: stomach
The exocrine cells secrete the chemical into the lumen (an empty cavity) that surrounds the collecting duct
ex: sweat, salivary, and mammary glands are all exocrine gland structures
65
Features of the Endocrine System
1. endocrine glands are ductless (the diff. between endo and exo secretion)
2. endocrine glands have rich blood supply
3. hormones, products of endocrine glands, are secreted into the bloodstream
4. hormones can travel in blood to every cell the body
5. Hormone receptors are binding sites for specific hormones in the membrane or in the cell
66
Major Endocrine Structures: Hypothalamus
control of hormone secretions
67
Major Endocrine Structures: Pineal Gland
reproductive maturation; body rhythms
68
Major Endocrine Structures: Pituitary Gland
Anterior Pituitary:
Hormone secretion by thyroid, adrenal cortex, and gonads; growth
Posterior pituitary:
water balances; salt balance
69
Major Endocrine Structures: Thyroid
growth and development; metabolic rate
70
Major Endocrine Structures: Adrenal Glands
Adrenal Cortex: outer part
- salt and carbohydrate metabolism; inflammatory reactions
Adrenal Medulla: inner core
- emotional arousal
71
Major Endocrine Structures: Pancreas
islets of langerhans
sugar metabolism
72
Major Endocrine Structures: Gut
digestion and appetite control
73
Major Endocrine Structures: Gonads (testes/ovaries)
body development; maintenance of reproductive organs in adults
74
4 Classes of Hormones
1. Protein and peptide hormones (polypeptides) -- amino acid-based
2. steroid hormones (3 rooms and garage) -- made of 6-carbon rings and 1 5-carbon ring
3. monoamines
4. lipid-based hormones (prostaglandins)
***they differ in how they release hormones, how they move thru blood, where their target receptor is, and their biological/cellular response
75
Peptide and Protein Hormones
Hormones that are made up of a few amino acids = peptide hormones (less than 50)
- bigger ones made of 50 amino acids
***they are soluable in blood (dissolves in blood) --- doesn't need carrier proteins
Large protein hormones: growth hormones - 200 amino acids
- can have a half-life of 20-30 mins (greater than 50 amino acids)
small peptide hormones: thyroid-releasing hormones -- 3 amino acids
- they can have a half-life of 5 minutes
- less than 50 amino acids
***GH = Protein Hormone
***TRH = TRH (thyrotropin-releasing hormone)
76
Pituitary Gland Structure
the Hypothalamus and the Pituitary gland together regulate every body system
- the hypothalamus is important and influences peripheral systems using the pituitary
pituitary made of:
- posterior pituitary
- Anterior pituitary
77
Anterior Pituitary
***acts as a portal system (has specialized vascular arrangement with 2 capillary beds separated by a portal vein)
***chemical messengers in the blood stimulate the endocrine cells to release hormones
(the capillary beds are the blue twisty things)
chain:
hypothalamus has neurons --> releasing factor with portal veins --> endocrine cells secrete hormones
78
Posterior Pituitary
***neurons project down to the posterior pituitary and stimulate release (directly)
chain: hypothalamus has neurosecretory cells that secrete the hormone
79
Hypothalamic Hormones: Peptide Hormones (releasing of inhibiting hormones)
Releasing Hormones: ends in RH
- Gonadotropin releasing hormone (GnRH)
- Growth hormone-releasing hormone (GHRH; somatocrinin)
- Croticotropin-releasing hormone (CRH)
- Thyrotropin-releasing hormone (TRH)
- Prolactin-releasing hormone (PRH)
- Kisspeptin (onset of puberty)
Inhibiting Hormones: ends in IH
- Growth-hormone inhibiting hormone (GHIH; somatostatin)
- Gonadotropin inhibiting hormone (GnIH)
- Dopamine (prolactin inhibitory hormone)
- hypocretin (sleep, metabolic function)
80
Pathway of the hormones - IMPORTANT
The hypothalamus releases releasing or inhibiting hormone (small peptide hormones --ex: GnRH)
- those get secreted into the pituitary portal vein and then go thru to the anterior pituitary gland (that releases tropic hormones like LH --- peptide hormones too)
- the tropic hormone stimulates the endocrine gland and the endocrine cells releases hormones and then they go thru the bloodstream and bind to their target tissue
ex: GnRH are in the hypothalamus and then go into the portal vein, GnRH goes into the pituitary portal vein into the anterior -- then the endocrine cells secrete LH and FSH
- then LH and FSH travel into the gonads where they can regulate the release of other hormones
- tissues that are feminized (get estrogen and progestin)
- tissues that are masculinized (androgens)
portal system = pituitary portal vein, anterior pituitary, endocrine cells
81
GnRH example
***abnormal regulation can impact puberty and fertility
- they have negative feedback loops for regulation of hormones
82
GHIH (somatostatin) and GHRH example
they secrete hormones
- then the endocrine gland secretes GH
- then GH binds to the liver: secretes insulin-like growth factor
- GH also binds to other cells throughout the body
Growth Hormone Deficiency:
too much = really tall
too little = short
- pituitary gland makes GH
symptoms of GH deficiency:
- depression, lack of concentration, poor memory, anxiety
83
CRH example
CRH in hypothalamus secretes hormone into anterior pituitary
- endocrine cells secrete ACTH
- ACTH binds to the adrenal gland
- adrenal gland secretes cortisol
cortisol: stress response hormone
- can suppress appetite
- increase anxiety
stress hormones = CRH and ACTH
84
TRH example
TRH in hypothalamus
- TRH secreted
- endocrine cells secrete TSH
- TSH binds to thyroid gland
- Thyroid gland secretes TH (T3 and T4)
T3 and T4 regulate your body's temperature, metabolism and heart rate
- they increase rate of glucose oxidation
- T4 is a lot more released than T3
de-iodination: process where once your thyroid releases T4 into your blood, certain cells can transform it into T3
85
Hyperthyroidism vs. Hypothyroidism
Hyperthyroidism: too much thyroid hormone
Grave's disease: immune cells attack the thyroid gland which responds by secreting an excess amount of thyroid hormone
- causes thyroid gland to get big and increased metabolism
symptoms:
- fast heart rate, sweating, high blood pressure, fatigue, weight loss, hair loss, don't like heat, heart palpitations, light or absent periods, increased bowel movements
Hypothyroid disease: too little thyroid hormone (not enough)
- fatigue, weight gain, puffy face, don't like cold, muscle pain, dry skin, thinning hair, not a lot of sweating, bad periods, depression, goiter, decreased heart rate, constipation
86
PIH and PRH Example
the cells in the hypothalamus secrete PIH (dopamine) and PRH
- endocrine cells secrete prolactin
- prolactin binds to breast tissue
ex: prolactin - MILK PRODUCTION
- released in response to PRH/TRH
- known for its role in lactation but first discovered to promote corpus letuem in rats
helps with reproduction, growth and development, water balance, steroid-sensitive tissues
***involved in milk production but not milk release
87
Posterior Pituitary Hormones - Pathway
direct -- hypothalamus releases hormones and they travel to the posterior pituitary
- the posterior stores them (doesn't make hormones) and then releases them directly into the bloodstream
- oxytocin and vasopressin (AVP) get released
- oxytocin goes to uterine muscles, mammary glands (causes contraction) - RELEASE OF MILK
- vasopressin goes to the kidney (causes vasocontriction and water retention)
88
Central Brain Actions
oxytocin and vassopressin regulate social cognition and behavior
oxtytocin and vassopresin can also be used for therapy for mental disorders, autism, social anxiety disorder, personality disorder, schizophrenia
89
Oxytocin Milk Letdown
the baby sucks on the mom's nipple which causes the mom's brain activity -- nerve impulses sent to the hypothalamus
- hypothalamic cells get sensory info from the periphery
- cells in the hypothalamus produce oxytocin and release it from the posterior pituitary
- the oxytocin causes the cells of the mammary glands to contract by releasing milk
- the baby gets milk and this continues until the baby is done
90
Steroid Hormones
fat soluable -- they move easuly thru membranes
***intracellular properties
Not water soluable -- they can't travel thru water so they need carrier properties in the blood
- carrier proteins protect against degradation (like sex steroid hormone binding globulin and serum albumin)
- they travel thru blood -- when they hit the target cell, they get released from their carrier protein and bind to the receptor or enter cell
***the response can be slow (or fast)
- the steroid impact can last awhile
91
Steroid Receptor Structure
the steroid hormones act by binding to steroid receptors
steroid receptor structure: they have
- binding domain (site), DNA binding site
- the receptors interact mostly with DNA
- transcription altered by hormone binding
- they're activated by phosphorylation or by ligand domain
important: neurotramitters lead to phosphorylation (ex: dopamine)
- they're able to respond more than hormone
92
Organization of Steroid Receptors
nuclear hormone receptors share a similar structure made of 4 functional domains:
A/B region: ligand-independent activation, activation function 1
C region: DNA-binding domain
D region: hinge region (allows for conformational change)
E region: ligand-binding domain, activation function 2
pathway:
- steroid receptor found in cytoplasm -- then gets dimerized
- then they go thru the nuclear pore
- then coactivators float around, bind DNA once steroid receptor binds, brings in RNA polymerase
- RNA polymerase transcribes the RNA into mRNA
- the mRNA gets translated into a protein
93
Actions of Steroids on Target Tissues depend on:
1. levels of steroid hormones (if you lack hormone, there's no response)
2. levels of steroid receptors (if you have too many or don't have enough -- not a big response)
3. levels and combinations of co-regulatory proteins (co-activators (proteins) and co-repressors -- they're proteins)
94
5 Classes of Steroid Hormones
1. Androgens: tesosterone, androstenedione, Dihydrotesosterone (DHT)
2. Estrogens: estradiol, estrone, estriol (all start with e)
3. Progestins: pregenolone, progesterone (both start with p)
4. Mineralocorticoids: aldosterone (good for water retention)
- aldosterone tends to promote Na+ and water retention, and lower plasma K+
(act in brain but we don't know a lot about its neutral basis)
5. glucocorticoids: corticosterone, cortisol
95
High Cholesterol
High cholesterol in someone's diet can result in clogged arteries
- high cholesterol in blood can cause high blood pressure and clogged arteries (also known as atherosclerosis) -- this results in heart disease and stroke
*Dr. Daly helped discover this research
- Dr. Daly found strong correlation between high blood pressure and having high cholesterol levels in the blood
***she isolated histones from animals to see their properties -- her work helped us understand how DNA is organized
***all steroid hormones are from cholesterol
96
Enzymes to Know
21- hydroxylase
5 alpha - reductase
HELP
97
Cholesterol Enzyme Pathway
3 pathways of cholesterol:
cholesterol --> progestin/progestogen ---> 21-hydroxylase --> glucocorticoids
cholesterol --> progesterone --? androgens testosterone --> 5 alpha-reductase ---> DHT
DHT (stronger androgen than tesosterone --- DHT is responsible for most of tesosterone's roles in the brain)
cholesterol --> progesterone --> andorgens --> aromatase --> estrogens
98
Testosterone and brain receptors
two pathways:
1. testosterone --> 5 alpha reductase --> dihydro-testosterone --> androgen receptors (in the brain)
2. testosterone --> aromotase --> estradiol --> estrogen receptors
99
Androgens and estrogens called sex hormones
they shouldn't be considered male or female hormones
- all male vertebrates make estrogens and progestins
- all female vertebrates make androgens
***but there are differences in the levels of these hormones between males and females
***the gonads produce high levels of androgens, but females have high levels of aromatizing enzymes that convert androgens (primary source of estrogens) into estrogens
100
Monoamines
two classes: catecholamines and indole amines
catecholamines (fight or flight): epinephrine (adrenaline), norepeniephrine (noardrenaline) and dopamine
- release of the hormones epinephrine and norepinephrine from the adrenal medulla (location of action) of the adrenal glands is part of the fight-or-flight response
indole amines: serotonin (5HT) and melatonin
- serotonin levels are high in pineal gland (location) during light and go away during dark when it's converted to melatonin
101
Catecholoamines list:
tyrosine, dihydroxypenylalanine (DOPA), Dopamine, Norepinephrine, and Epinephrine
Catecholamines pathway:
tyrosine --> DOPA --> Dopamine --> norepinephrine ---> epinephrine
*norepinephrine = attention
*dopamine = motivation
*epinephrine = stress response
102
Indole Amines
serotonin (5HT) (mood regulation) and melatonin (sleep regulation)
- serotonin levels are high in pineal gland during light and diminish during dark when its converted to melatonin
Light: cells convert TRP to serotonin
- tryptophan --> tryptophan hydroxylase --> aromatic amino acid decarboxylase --> serotonin
dark: serotonin --> melatonin
- norepinephrine increases cycylic AMP, which elevates synthesis of N-actely..
- N-actely --> N-acetyl serotonin --> HIOMT --> melatonin
103
Melatonin Example
**blue light disrupts conversion from serotonin to melatonin
- texting at night worsens teens' sleep, academic performance
blue light:
- the effects of blue light emitted from phone are more intense in a dark room
- short wavelength light can impact on daytime sleepiness (since it can delay melatonin release)
***as the day goes on, cortisol decreases and melatonin increases
104
Lipid-Based Hormones (Prostaglandins)
Prostaglandins:
- made from phospholipids
- a lot of different behaviors, especially in reproduction
- role in inflammation
ex: aspirin is a cox-2 inhibitor (cox-2 increases Prostaglandis)
- aspirin blocks masculinization of the brain in rats
105
How Hormones Act on Cells
polypeptides:
- they are surface receptors
- not lipid soluable -- they bind to receptors on surface of target cell
Amino acid derivatives:
- most not lipid soluable
- bind to receptors on surface of target cell
Steroids:
- in cell receptors
- lipid soluable -- often bind to receptors inside target cell
106
Steroid Hormone Receptor
steroid hormone goes into the cell, then it binds to a steroid receptor
- then that complex goes into the nucleus where DNA gets transcribed
- then made into mRNA and gets translated
- then leaves cell into ribosome
- then new protein made
107
Peptide Hormone Pathway Example
binds ligand
- peptides have to bind to something because they can't cross the membrane like how steroids can
receptors have at least 3 domains:
1. extracellular domain - binds hormone
2. transmembrane domain (in membrane)
3. cytoplasmic domain (inside the cell)
108
Peptide Hormone Pathway - DIRECT
Direct: cytoplasmic domain has enzymatic activity and can phosphorylate intracellular proteins directly when activated
*very fast activation pathway
signal molecule binds to transmembrane domain
-then phosphorylation happens
- then fully activated receptor (phosphorylated dimer)
then made into activated relay protein
- causes 2 cellular response
109
Peptide Hormone Pathway - INDIRECT
indirect: requires second messenger: middleperson
- these are couple to G proteins
g protein activates
- g couple protein, cAMP, and protein Kinase A
- goal is to get the enzyme phosphorylated
hormone →GPCR>G protein (Gs)->Adenylyl cyclase>CAMP> PKA>Phosphorylation>Cellular response
**this pathway used for amplification
indirect:
***has G-protein, activates, signaling cascade
- small peptide changes leads to massive signaling cascade
Psych 513
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