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stress and hormones Flashcards

1
Q

review of transcription and genetic translation

A
  1. to synthesize mRNA, the two strands of DNA must be unraveled by enzymes called HELICASES
  2. gene consists of unique linear sequence of DNA (special marker sequences denote the start/end points of each gene)
  3. PROMOTER/FACILITATORY region marks the start of the gene
  4. binding of a TRANSCRIPTION factor to promoter allows enzyme RNA POLYMERASE to attach to promoter and begin process of DNA SYNTHESIS
  5. sequence of RNA nucleotides (determined by sequence of nucleotides along the DNA) eventually determines sequence of AMINO ACIDS in the PROTEIN product of the gene
  6. DNA METHYLATION and HISTONE MODIFICATION are EPIGENETIC processes
  7. DNA methylation is a process of LONG-TERM GENE SILENCING that involves adding a methyl group to cytosines in the promoter version of a gene
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2
Q

transcription versus translation

A
  1. transcription:
    converts DNA into mRNA
  2. translation:
    decodes mRNA into amino acids, forming proteins essential for life functions
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3
Q

helicases

A

the enzymes that unravel the two strands of DNA

because DNA must be unraveled in order for it to be synthesized

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4
Q

genes consist of unique…

A

linear sequences of DNA

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5
Q

what marks the start of a gene?

A

promoter/facilitatory region

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6
Q

binding of what to the promoter allows RNA polymerase to attach and begin RNA synthesis?

A

transcription factor

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7
Q

what determines the sequence of amino acids in the protein product of the gene?

A

the sequence of RNA nucleotides

which is in turn determined by the sequence of nucleotides along the DNA

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8
Q

DNA methylation and histone modification are what kind of processes?

A

epigenetic

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9
Q

DNA methylation

A

process of long-term gene silencing

involves attaching a methyl group to cytosines in the promoter region of a gene

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10
Q

percentage of acute myocardial infractions (AMIs - heart attacks) are associated by patients to specific stress triggers?

A

48%

wars, natural disasters, anxiety-provoking events are associated with increase in heart attack rates

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11
Q

4 main questions in the behavioural endocrinology of stress

A
  1. why are some groups/individuals affected more severely by a potentially stressful event than others?
  2. are there differences among individuals in perception of stressors, perturbations to homeostasis, and physiological, psychological and behavioural responses to stressors?
  3. are stress responses always detrimental, or can they be adaptive in some circumstances?
  4. how can we measure stress?
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12
Q

homeostasis

A

the ability to maintain optimal conditions in the body

hormones are critical in this process

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13
Q

homeostasis involves the regulation of…

A

fluid and sodium balance

energy balance

eating

body mass and temperature regulation

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14
Q

stressors and homeostasis

A

stressors typically disrupt homeostasis

this affects the brain and behaviour

important to note: brain itself can perceive psychological factors as stressful and evoke a stress response

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15
Q

3 main sources of stressors

A
  1. environmental factors:
    temperature extremes, noises
  2. physiological factors:
    insufficient food quality/quantity, water deprivation
  3. psychosocial factors:
    maltreatment, social subordination, novel situations, lack of control
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16
Q

stress

A

any significant disturbance of homeostasis

ie. extreme temperatures, psychological factors

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17
Q

stressor

A

condition, agent or other stimulus that causes stress in an organism

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18
Q

stress-response

A

suite of physiological and behavioural responses that help to re-establish homeostasis

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19
Q

flight or flight response

A

automatic and endocrine responses that prepare an individual to battle or flee from real or perceived threat, attack or harm

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20
Q

examples of systems involved in mediation of stressors

A

glucocorticoids

sympathetic/parasympathetic transmitters

cytokines

metabolic hormones

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21
Q

systems that mediate stress operate as a nonlinear….

A

nonlinear, interactive network in which mediators UP and DOWN-REGULATE one another

depending on factors like:
1. concentration
2. location in the body
3. sequential and temporal patterning

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22
Q

two systems that constitute the major components of the stress response

A
  1. system involving epinephrine/adrenaline
    - from adrenal medulla
  2. system involving norepineprhine/noradrenaline
    - from adrenal cortex
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23
Q

emergency theory

A

within seconds of perceiving a stressor:

  1. sympathetic NS begins to secrete norepinephrine
  2. adrenal medullae begin to secrete epinephrine

immediate and non-specific component

involved in changes in:
a) cardiovascular tone
b) respiration rate
c) blood flow to muscles from trunk that support fight or flight behaviours

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24
Q

modern perspectives on stress = less likely to focus on fight or flight than on…

A

psychological features of stress

namely the degree of control the stressed individual has over the situation

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25
Q

exam: epinephrine and norepinephrine levels

A

epinephrine and norepinephrine levels increase and peak on the day of the exam

and then fall afterwards

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26
Q

parachute jump: hormone levels

A

cortisol, growth hormone and epinephrine all increase at the time of the jump

testosterone drops though

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27
Q

Hans Selye (1930s) is considered the…

A

founder of modern stress research

he was the first to observe epinephrine and glucocorticoid release in response to virtually any stressor (shows that stress response is NON-SPECIFIC)

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28
Q

common endocrine event underlying very different stress responses is…

A

release of glucocorticoids from adrenal cortex

caused by stressors as diverse as frostbite, formaldehyde exposure, hemorrhage

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29
Q

the two primary “stress hormones”

A

epinephrine and cortisol

despite facts that:

  1. their major endocrine functions involve metabolism
  2. circadian variation in these hormones occurs even in absence to stress exposure
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30
Q

both rats with ovarian hormone injection AND saline injection…

A

developed peptic ulcers, adrenal hypertrophy, regression of immune organs

was probably the handling of the animals in the lab that was causing them stress - not the injections

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31
Q

prolonged stress response - the _______ _______ syndrome

A

general adaptation syndrome

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32
Q

general adaptation syndrome consists of 3 stages…

A
  1. alarm reaction stage
  2. stage of resistance
  3. stage of exhaustion
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33
Q

alarm reaction stage

A

initial phase of body’s response to stress

stressor is perceived - body activates fight or flight response

^involves release of stress hormones (epinephrine, cortisol)

physiological changes occur rapidly (increased heart rate, heightened awareness, mobilization of energy reserves)

all to prepare the body to cope with the stressor

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34
Q

stage of resistance

A

if stressor persists beyond initial alarm reaction stage…

body enters stage of resistance

during this phase, body tries to adapt to ongoing stressor

by maintaining elevated levels of hormones and physiological responses

body tries to cope with stressor and restore homeostasis

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35
Q

stage of exhaustion

A

if stressor persists for extended period of time OR if body’s resources become depleted…

stage of exhaustion occurs

body’s ability to cope with stressor diminishes

physiological resources are depleted

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36
Q

Chrousos definition of stress

A

“the recognition by the body of a stressor and therefore, the state of heightened homeostasis. this way the stressors are threats against homeostasis; and adaptive responses are the body’s attempt to counteract the stressor and reestablish homeostasis”

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37
Q

Sapolsky definition of stress

A

“anything that throws your body out of homeostatic balance. considered together, stress is the sum of all nonspecific effects of factors that can act on the body to increase energy consumption above some resting, or basal, level.

in the short term, the stress response is adaptive and helps individuals cope with emergency situations; in the long term, the stress response tends to be maladaptive”

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38
Q

3 limits to the homeostatic concept of stress

A
  1. doesn’t address issue that PSYCHOLOGICAL stressors can evoke a full stress response; this psychological stress response actually causes HOMEOSTATIC IMBALANCE in an individual, rather than restoring it
  2. doesn’t account for INDIVIDUAL VARIATION in perception of stressors
  3. for a definition of stress to be useful, must address how the SAME STIMULUS can be STRESSFUL to one individual and PLEASURABLE to another
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39
Q

stress is a condition in which individuals are aroused by…

A

aversive stimuli

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40
Q

for an event to be defined as stressful, the individual must…

A

perceive it as aversive

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41
Q

a stressful event involves an individual’s lack of…

A

perception of control over the aversive stimuli

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42
Q

predictive homeostasis

A

the response range that comprises daily and seasonal variation in a given hormone

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43
Q

reactive homeostasis

A

range of mediator fluctuations necessary to respond to threats

allostasis

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44
Q

homeostatic overload

A

values above the reactive homeostasis range

allostatic load/overload

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45
Q

homeostatic failure

A

mediator values below the predictive homeostasis range

allostatic load/overload

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46
Q

physiological effects of stress response: within seconds…

A
  1. sympathetic NS secretes norepinephrine and epinephrine

from adrenal medulla

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47
Q

physiological effects of stress response: after release of epinephrine and norepinephrine…

A

HPA axis: hypothalamus releases cortico-tropin releasing hormone

this stimulates release of adrenocorticotropin hormone from anterior pituitary gland

within minutes, adrenal cortex begins to secrete glucocorticoids

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48
Q

3 main events of hormone release immediately after stressor presentation

A
  1. sympathetic NS (adrenal medulla) releases norepinephrine and epinephrine
  2. hypothalamus releases corticotropin-releasing hormone - stimulates release of adrenocorticotropin hormone from anterior pituitary
  3. adrenal cortex begins to secrete glucocorticoids
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49
Q

other hormones secreted from endocrine tissues during a stress response

A

prolactin

urocortin

glucagon

thyroid hormones

vasopressin

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50
Q

7 steps of the physiological stress response - zebra being hunted example

A
  1. need quick energy supply in order to sustain sprint back to a safe place
  2. immediate release of catecholamines (NE and EP) raises respiration and cardiovascular rates within seconds - body requires increased energy availability to sustain these high rates
  • immediate increase in glucose and oxygen levels available in the blood
  • EP increases delivery of oxygen to tissues and raises sympathetic tone
  1. glucocorticoids (secreted within minutes - likely only after stressful event) act on metabolic pathways to replenish energy reserves used to escape predator
  2. rapid effects of glucocorticoids operate via non-genomic pathways to affect behavioural stress responses
    - although genomic pathways mediate some of the long-term effects of stressors
  3. responses to injuries that might curtail movement (ie. pain, inflammation) are inhibited by the stress-induced release of endorphins and endocannabinoids
  4. energetically expensive activities like growth and reproduction, and some components of immune function, are also suppressed until after emergency has passed
  5. other components of immune function, like trafficking of immune cells to the skin where injuries might occur, are enhanced during stressful events
51
Q

what happens to parasympathetic tone and metabolic rate as stress response subsides?

A

parasympathetic tone increases

metabolic rate returns to baseline

52
Q

stress response: release of catecholamines does what?

A

catecholamines: NE and EP

raises respiration and cardiovascular rates within seconds

(body needs increased energy availability to sustain these high rates)

53
Q

raised respiration and cardiovascular rates require…

A

increased energy availability

immediate increase in available levels of glucose and oxygen in blood

EP increases delivery of oxygen to tissues, raises sympathetic tone

54
Q

rapid effects of glucocorticoids operate via…

A

non-genomic pathways

to affect behavioural stress responses

(although genomic pathways mediate some long-term effects of stressors)

55
Q

what energetically expensive activities are suppressed until after the emergency has passed?

A

growth

reproduction

some components of immune function

56
Q

stress response: endorphins and endocannabinoids do what?

A

stress-induced release of endorphins and endo-cannabinoids

in response to injuries that might curtail movement (pain, inflammation)

57
Q

adaptive effects of proper stress response

A
  1. increased immediate availability of energy
  2. increased oxygen intake
  3. decreased blood flow to organ systems not needed for movement
  4. inhibition of energetically expensive processes that are not related to immediate survival, such as digestion, growth, immune function and reproduction
  5. decreased pain perception
  6. enhancement of sensory function and memory
58
Q

stress response: both the predator and prey…

A

experience similar acute stress responses during the chase

despite their disparate roles

another example of non-specificity of stress response

59
Q

epinephrine is what kind of molecule?

A

polar

60
Q

epinephrine, as a polar molecule, doesn’t easily…

A

cross the blood-brain barrier

so glucocorticoids are good candidates for mediating behavioural effects of stress

61
Q

evidence for glucocorticoid importance in behaviour

A
  1. these steroid hormones are released in response to numerous stressors
  2. steroid hormones can easily diffuse past blood brain barrier
  3. there are glucocorticoid receptors in several brain regions
62
Q

implication of a hormone in behaviour requires evidence of…

A

hormonal signalling in the CNS

63
Q

not only glucocorticoids act in the CNS during stress response - what else does?

A

CRH (a polypeptide)

64
Q

corticotropin releasing hormone (CRH) mediates aspects of stress response…

A

adaptive and pathological responses

actes in hypothalamus and amygdala

65
Q

CRH in hypothalamus

A

mainly involved in regulation of HPA axis

66
Q

CRH in amygdala

A

involved in mediating anxiety responses

67
Q

transgenic mice that express high levels of CRH in the amygdala…

A

are more ANXIOUS in a novel environment than control mice

same is true of wild-type mice/rats that are injected with exogenous CRH

68
Q

CRH receptor antagonists decrease…

A

anxiety normally associated with alcohol withdrawal and social defeat in rats and mice

69
Q

high levels of CRH expressed in transgenic mice also decrease…

A

female sexual receptivity

this isn’t reversed by adrenalectomy

70
Q

CRH1 knockout mice…

A

were less anxious

71
Q

CRH1 receptors seem to mediate…

A

hormonal, behavioural, and nociceptive responses to stress

appear to be involved in NEGATIVE FEEDBACK regulation of the HPA axis

72
Q

role of CRH1 in negative feedback - hippocampus and maybe amygdala

A

notion that hippocampus and maybe the amygdala provide role in negative feedback during stress response

supported by CRH1 receptors that are located in these regions

receptors are presumably inactivated by conditional gene inactivation

73
Q

activation of CRH2 receptor suppresses…

A

food intake in food-restricted and freely fed mice

suggests a mechanism for how stress suppresses appetite

74
Q

how many CHR2 genes exist in mammals? what happens if all three are deleted?

A

three

if all three are deleted, knockout mice fail to recover from stress

display enduring anxiety responses

75
Q

corticosteroid receptors in hippocampus

A

type I - mineralocorticoid receptors (MRs)

type II - glucocorticoid receptors (GRs)

76
Q

mineralocorticoid receptors

A

type I corticosteroid receptors

have higher affinity for circulating glucocorticoids

usually engaged under baseline conditions

activation of these receptors is thought to modulate homeostatic balance

but, as glucocorticoids increase during a stress response, low-affinity GRs are activated

77
Q

glucocorticoid receptors

A

type II corticosteroid receptors

low-affinity receptor (ie. more specific to cortisol)

provides negative feedback and brings the stress response back under control

78
Q

role of aldosterone in stress response

A

aldosterone is a mineralocorticoid

central role in homeostatic regulation of:
1. blood pressure
2. plasma sodium (Na+)
3. potassium (K+)

79
Q

are endo-cannabinoids involved in stress response? if so, how?

A

yes

endo-cannabinoids mediate the effects of glucocorticoids on stress response

via synaptic mechanisms

80
Q

glucocorticoid and endo-cannabinoid interactions

A
  1. glucocorticoids bind to membrane-bound glucocorticoid receptors
  2. g protein signalling cascade induces endo-cannabinoid ligand production
    (no gene transcription in this process - non-genomic)
  3. endo-cannabinoid ligand molecules are released into the synapse
  4. they bind to CB1 cannabinoid receptors on GABA-ergic terminals to inhibit GABA secretion
  5. the decrease in GABA disinhibits norepinephrine secretion and modulates stress responses

remember: GABA is an inhibitory neurotransmitter AND there are glucocorticoid receptors in the membrane too

81
Q

although ACTH is the pituitary hormone that is most often associated with stress, several other pituitary hormones, including… play important roles

A

vasopressin

prolactin

endorphins

enkephalins

82
Q

vasopressin role in stress

A

increased blood concentrations of vasopressin in response to stress

directly affects behaviour

ENHANCES MEMORY CONSOLIDATION and RETRIEVAL

increases AGGRESSION in defence

works in concert with CRH to augment release of ACTH from anterior pituitary

83
Q

urocortin role in stress

A

urocortin is a CRH-like neuropeptide

amplifies stress signals by activating CRH receptors

84
Q

prolactin role in stress

A

suppresses reproduction temporarily

by acting at multiple sites within the hypothalamus-pituitary-gonadal (HPG) axis

85
Q

endorphins/enkephalins role in stress

A

provide relief from PAIN

suppress gonadotropin-releasing hormone (GnRH)

thereby inhibit reproductive function

86
Q

glucagon role in stress response

A

alpha cells of endocrine pancreas are stimulated to secrete glucagon

glucagon increases energy availability

beta cells of pancreas are inhibited by glucagon - from secreting insulin

87
Q

adaptive-stress response

A

ideally, stress reponse is initiated by stressful stimuli

and then the system deactivates

negative feedback

88
Q

what factors can deregulate the normal stress response?

A
  1. chronic stress
  2. genetic differences in glucocorticoid receptor numbers/subtype
  3. other individual diffs in:
    a) endocrine secretion
    b) responsiveness
    c) carrier-binding proteins

this provokes inappropriate/pathological stress response

89
Q

prolonged stress shifts the useful, adaptive short-term stress response to a…

A

pathological condition

can jeopardize health, economics, survival

90
Q

4 health conditions associated with high levels of childhood stress

A
  1. asthma
  2. depression
  3. diabetes
  4. cardiovascular conditions
91
Q

acute versus pathological effects of long-term stress responses

A

actue stress response:
a) shift from energy storage to energy use
b) increased cardiovascular tone
c) inhibited digestion
d) inhibited growth
e) inhibited reproduction
f) altered immune function and inflammatory responses
g) enhanced cognition
h) enhanced analgesia

pathological state associated with chronic stress:
a) fatigue; myopathy; steroid diabetes
b) hypertension
c) peptic ulcers
d) psychosocial dwarfism
e) impotence; anovulation; loss libido
f) impaired disease resistance; cancer
g) accelerated neural degeneration during aging

92
Q

brain: effects of pathological state of stress

A

dendritic atrophy

impaired neurogenesis

impaired synaptic plasticity

enhanced benzodiazepine tone

93
Q

heart: effects of pathological state of stress

A

basal hypertension

sluggish responses to and recovery from stress

pathogenic cholesterol profile

94
Q

ovary: effects of pathological state of stress

A

decreased levels of gonadal hormones

increased risk of anovulation and miscarriage

95
Q

immune system: effects of pathological state of stress

A

basal immunosuppression

decreased immune responsiveness to challenge

96
Q

adrenal glands: effects of pathological state of stress

A

elevated basal levels of glucocorticoids

sluggish response to and recovery from stress

feedback resistance

97
Q

testis: effects of pathological state of stress

A

testicular trophy

decreased levels of hormones of the gonadal axis

98
Q

myopathy: pathological effects of stress response

A

muscle loss

with prolonged glucocorticoid secretion

inevitable

stress-induced breakdown of glycogen and lipids to elevate blood glucose concentrations cannot continue indefinitely

99
Q

severe cases of stress-induced myopathy can induce…

A

irreversible loss of muscle cells in the heart

100
Q

myopathy is an example of what we called ____ ___ ____ stress

A

Wear and Tear

101
Q

reproductive function: pathological effects of stress response

A

reproductive function is inhibited by high glucocorticoid concentrations

and psychological stress can reinforce its effects

psychological stress of experiencing infertility, in addition to stress of treatments, causes more stress and consequently reinforces the infertility

102
Q

inhibited digestion: pathological effects of stress response

A

prolonged inhibition of digestion during stress can lead to:

a) ulcers
b) chronic IBS

in concert with immune suppression - can allow bacteria to attack stomach

103
Q

growth and repair processes: pathological effects of stress response

A

ie. fingernails are more flimsy/brittle, hair grows slower during stressful periods of life

chronic stress delays cutaneous wound healing

104
Q

glucocorticoid inhibitory effects on broad range of immune responses

A

because of their inhibitory effects on multiple types of immune cells

glucocorticoids = remarkably efficacious in managing many of the ACUTE DISEASE MANIFESTATIONS of inflammatory and autoimmune disorders

105
Q

example of an autoimmune disease that’s treated with glucocorticoids

A

lupus

106
Q

chronic stress alters the ____ and ____ of the brain

A

structure and function

a) reduced neurogenesis

b) retraction of dendrites of hippocampal and cortical neurons

c) but expansion of dendrites in basolateral amygdala

d) increased inflammation in the brain

107
Q

structure/function of which brain areas are particularly altered by chronic stress?

A

hippocampus

amygdala

PFC

108
Q

strange: stress usually results in dendrite retraction, but in what area is it associated with physical expansion of dendrites?

A

basolateral amygdala

109
Q

changes in brain following chronic stress are potential ways in which stress can lead to…

A

cognitive dysfunction

depression

110
Q

why do our minds go blank when we get stressed? ie when taking a test

A

because stress deactivates the PFC

adaptive: to not be scared by a predator/threatening situation

111
Q

hippocampus and HPA regulation: hypercorticolism

A

hippocampus = key site of HPA axis negative feedback

and hippocampus is damaged by chronic stress

vicious cycle can develop

  1. prolonged elevated glucocorticoids cause hippocampal dysfunction and impair negative feedback
  2. this in turn leads to ever-increasing glucocorticoid concentrations
112
Q

blunted HPA axis responsiveness

A

normal response has a peak in glucocorticoids and then a sharp decrease

blunted/disrupted negative feeback:
a) glucocorticoids don’t reach the peak that occurs in normal response

b) they stay elevated for too long

113
Q

hippocampus and HPA regulation: differences due to SOCIAL DOMINANCE

A

feedback system implicated in cortisol response can vary according to social position

stress has diff effects on dominant/subordinate baboons

114
Q

diff effects of stress on dominant versus subordinate baboons

A

after stressful event:

  1. dominant animals display ELEVATED CORTISOL
    - but because they have an efficient HPA axis feedback system, cortisol concentrations return to baseline faster
  2. subordinate individuals have blunted sensitivity to CRH in anterior pituitary
    - thus, a similar stressful stimulus results in LOW CORTISOL RESPONSE
    - but also LONG TERM ELEVATION OF GLUCOCORTICOIDS

may ultimately harm these individuals

115
Q

for something to be considered stressful, individuals must… but…

A

perceive the stressor as aversive

but humans = exposed to diff circumstances that aren’t necessarily perceived as stressful but that can have deregulatory effects on physiological responses that aim to restore homeostasis

adversity can be conceived as the exposure to harmful/threatening stimuli, or the absence of stimulation needed for typical development

116
Q

two ways to conceive ADVERSITY

A
  1. exposure to harmful/threatening stimuli
  2. absence of stimulation needed for typical development
117
Q

adverse exposure forms

A

exposure to harmful/threatening stimuli

or absence of stimulation needed for typical development - which in turn will require SIGNIFICANT ADAPTATION by the infant

118
Q

two effect levels of adverse exposure forms

A
  1. direct effects:
    a) family psychiatric problems
    b) maltreatment
    c) family functioning
    d) witnessing/suffering domestic violence
  2. contextual effects:
    a) growing up in poverty
    b) living in violent areas
    c) occupational disruptions
119
Q

Romania’s example of negligence: the policy

A

70’s-80’s : President Nicolae Ceausescu created policy aimed at increasing population

plan was to increase pop from 23 to 30 million by 2020

prohibition of contraception and criminalization of abortion

specific state laws for women’s health, requirements for examination by state doctors

120
Q

Romania’s example of negligence: the policy’s effects

A

it “worked”

birth rate increased from 1.9 births per woman to 3.6 in one year

but people were poor - no money to support children

left them on street

121
Q

Romania’s example of negligence: orphanages

A

government created orphanages to house the abandoned children

employees of these shelters = instructed not to show any affection to babies

if crying, told to ignore them until they “learned it wouldn’t get them attention”

slept in identical cradles, lined up in large sheds - little human contact

122
Q

The Bucharest Project

A

randomized controlled trial of foster care as an ALTERNATIVE to institutionalized rearing of abandoned children

changes in ANS and HPA axis measurements during 2 tasks

a) two social stressors (the Trier Social Stress Test - TSST) which includes preparation, speech, and math portions

b) nonsocial stressor (frustration task)

assigned to 3 intervention groups:

a) deprived from care

b) high quality foster care intervention

c) typically developing Romanian

123
Q

The Bucharest Project findings

A

group differences in ANS reactivity to stressor tests

care as usual group
foster care group
never institutionalized group

  1. children who remained in institutional care exhibited significantly blunted HPA AXIS REACTIVITY
  2. children who remained in institutional care exhibited significantly blunted SYMPATHETIC RESPONSE
124
Q

importance of child attachment for the HPA axis

A

parent and child relationship is crucial for infants

secure versus insecure attachment

children with more secure attachment have better stress response

Psyc 342 (10 decks)

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