Lecture 3 Flashcards by Sara Richmond

What is stress?

A Syndrome produced by Diverse Nocuous Agents (Nature, 1936) Nocuous Agents: cold, injury, excessive exercise

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“General Adaptation Syndrome”

Phase 1: atrophy of the thymus, loss of fat and muscle tone, drop in body temperature
Phase 2: hypertrophy of the adrenal cortex, growth ceases, gonads atrophy
Phase 3: exhaustion, succumb to symptoms of the first stage

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STress is A challenge to the organism that activates the _____________

autonomic nervous system or HPA axis

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three kinds of stress

physciological
emotional
stresser

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What are the responses of the Hypothalamus-pituitary- adrenal (HPA) axis

Increase in cardiovascular tone
• Increase in blood pressure
• Mobilization of stored energy to muscle
• Transient enhancements of immunity
• Inhibition of costly, long-term processes
such as growth & reproduction

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___________ (HPA) axis

Hypothalamus- pituitary-adrenal

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Magnocellular neurons of the supraoptic nucleus (SON) & paraventricular nucleus (PVN) make _____________

vasopressin VP

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Corticotropes that express CRH-R make ______________________

adrenocorticotrophic hormone (ACTH)

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Parvocellular neurons of the parvocellular nucleus make

CRH

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ACTH is synthesized from pro-opiomelanocortin (POMC)POMC processed into ______________

3 active proteins: ACTH, melanocyte stimulating hormone (MSH), & endorphin

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Corticotropes secrete_____________

ACTH

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Keratinocytes secrete ____________ in response to UV light from the sunàmelanin dispersal from melanocytes (tanning)

a-MSH

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• Appetite-suppressing neurons in arcuate secrete ____________to control food intake

a-MSH

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• Other neurons in the CNS produce __________ an endogenous opioid that suppresses pain

endorphin,

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Hypothalamus-pituitary-adrenal axis is regulated by: (3 things)

negative feedback
circadian rhythms
stressors (physiological and emotional)

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Capsule and Zona glomerulosa produce what steroid ______________________

Mineralocorticoids (e.g. aldosterone)

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Zona fasciculata produces ___________

Glucocorticoids (e.g. cortisol)

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Zona reticularis produces _____________

Androgens (e.g. DHEA, androstenedione)

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Adrenal Medulla produces ___________

Catecholamines (e.g. epinephrine)

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These four areas make up the \_\_\_\_\_\_\_\_\_\_\_\_\_
Capsule
Zona glomerulosa
Zona fasciculata
Zona reticularis

adrenal cortex

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Production of glucocorticoids and mineralocorticoids requires what two enzymes

21- hydroxylase & 11beta-hydroxylase

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______________ (C21)(e.g. aldosterone)

Mineralocorticoids

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______________(e.g. cortisol in humans and corticosterone in rodents)

• Glucocorticoids (C21)

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_____________Dehydroepiandrosterone (DHEA), androstenedione

• Androgens (C19):

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What is the chain of events for Mineralocorticoids (e.g. aldosterone)

- cholesterol _ progestogens_ glucocorticoids

What is the chain of events for Glucocorticoids (e.g. cortisol) ________________

cholesterol________progestogens_________glucocorticoids

What is the chain of events for Androgens (e.g. DHEA, androstenedione)

- cholesterol_progestogens_androgens

Notice that hormones in the adrenal cortex begin as

cholesterol

What would happen if glucocorticoid production were compromised?

- an accumlication of precursors - less cortisol/ aldosterone - elavated testosterone and estrogens

(type I) mineralocorticoid receptors (MRs) __________ - activated by cort and aldosterone in low and high concentrations - expression restricted to hippocampus, central nucleus of the amygdala (CeA), lateral and medial septum (LS and MS)

high affinity

type II) glucocorticoid receptors (GRs)____________ - activated when cort is high - Nearly ubiquitously expressed - GRs in PVN and anterior pituitary mediate negative feedback of the HPA axis

low affinity,

Which receptor is - activated by cort and aldosterone in low and high concentrations

(type I) mineralocorticoid receptors

Which receptor is. activated only when cort is high

type II) glucocorticoid receptors (GRs)

_________ is an integral part of the sympathetic nervous system

Adrenal Medulla

In the Adrenal Medulla, _________secrete epinephrine >> noreprinephrine >> dopamine as neurotransmitters

Chromaffin cells

In the adrenal medulla chromatin cells secrete

epinephrine >> noreprinephrine >> dopamine

what is the progression of Catecholamines (e.g. epinephrine) produced in adrenal medulla

- tyrosine_______dopamine_______norepinephrine________-epinephrine

Three main types of Adrenergic Receptors

- α1 & α2 greater sensitivity to NE norepinephrine | - ß2 bind almost exclusively to Epinephrine

Specific G-proteins confer different effects, e.g. opposite effects on __________

smooth muscle

Adrenergic Receptors Allow tissue-specific response to a ------------

singular stimulus

___________are typically fast changes

Adrenergic Receptors

__________ ARe Typically slow transcriptional changes

Glucocorticoid and Mineralocorticoid Receptors

___________Increases blood pressure, reabsorption of sodium and secretion of potassium

Aldosterone:

____________ Increases blood pressure

• Vasopressin:

__________: Increases blood pressure, blood sugar levels, increased heart rate, cardiac contractility, relaxation of smooth muscle in the airways. Reduces glucose uptake by tissues other than the brain.

• Epinephrine

________________ Increases blood glucose via gluconeogenesis. Reduces glucose uptake by tissues other than the brain. Increases lipolysis to use fat as an energy source in other tissues to conserve glucose for the brain. Anti- inflammatory and immunosuppressive effects. Suppresses reproduction.

• Cortisol:

Why would cortisol peak first thing in the morning?

Example of predicting physiological needs

Memory: the hippocampus expresses both

MR and GR | * stress is involved in memory

Less glucocorticoid synthesized, _______ | Less glucocorticoid leads to__________

recall is worse. a higher rate of forgetting Cortisol replacement restored recall to level of placebo

Sonia Lupien, PhD research was inhibiting the enzyme which results in the production of _______________

cortisol and corticosterone

Stress improves performance up to a point:

U shaped curve

What does Too much cortisol result in

higher GR activation and dysfunction

Access of glucocorticoids to receptors in hippocampus and other brain regions is regulated by 3 factors:

- Corticosteroid binding globulin(CBG) - MultipledrugresistanceP-glycoprotein (MDRpG) - 11b-hydroxysteroid dehydrogenase (11 HSD).

___________________binds natural glucocorticoids but not the synthetic glucocorticoid dexamethasone.

Corticosteroidbindingglobulin(CBG)

Conversionofcortisolintolargelyinactive cortisone by ________________

11b-hydroxysteroid dehydrogenase (11 HSD).

_____________, MDRpG at the blood-brain barrier actively transports synthetic steroids (such as dexamethasone), and to some extent 17- hydroxylated natural steroids, such as cortisol, out of the brain so that they do not enter very readily. It will be very effective at low doses, but cortisol will enter the brain when levels very high.

MultipledrugresistanceP-glycoprotein (MDRpG)

A stress response can be observed in situations that are:

- novel, unpredictable, not controllable by the individual, and/or a social evaluative threat (possibly leading to rejection)

Social Stressors – Consequences for survival ____________ experience a greater social stress - unpredictable, not controllable by the individual, and/or a social evaluative threat (possibly leading to rejection)

Lower status on a social heirarchy:

____________ aka Primary Adrenocortical Insufficency

Addison’s Disease,

Adisons diseases Most commonly caused by autoimmune destruction of the cortex both

aldosterone and cortisol are deficient.

Symptoms of aldosterone deficiency:

- K+ retention (hyperkalemia), due to lower K+ loss in the urineàdisturbs cardiac function - Na+ depletion (hyponatremia), due to urinary loss of Na+ à reduces blood volume & lowers blood pressure (hypotension).

Symptoms of_________ deficiency: - poor response to stress - hypoglycemia caused by reduced gluconeogenic activity

cortisol

__________ due to excessive ACTH

3. Hyperpigmentation

____________ | Most commonly caused by mutations in enzymes that convert progestogens to glucocorticoids

Congenital Adrenal Hyperplasia

Hypoaldosteronism- salt balance “salt-wasting” Hypocortisolism_stress reponse Excess androgen production_

- salt wasting \ - stress response - masculinization

Treatment for congenital adrenal hyperplasia

Treatment can include: • providing replacement glucocorticoid, mineralocorticoid, extra salt • modulating the HPG axis by delaying puberty to allow for bone growth, modulating androgen or estrogen receptor signaling

Describe the cell, tissues, and receptors in the hypothalamus- pituitary-adrenal axis

3 arms: Posterior Pituitary (magno), sympathetic nervous system (ACh), Anterior pituitary (parvo) Adrenergic receptors and MR/GR

Predict physiological consequences of physiological or psychological stressors

Overlapping functions of epinephrine and aldosterone, epinephrine and cortisol with different timing.