Week 4-Endocrinology

Question 1

What are the 6 Hypothalamic releasing and Inhibitory hormones?

Answer 1

1. Thyrotropin-releasing hormone (TRH)
2. Gonadotropin-releasing hormone (GnRH)
3. Growth hormone-releasing hormone (GHRH)
4. Growth hormone-inhibitory hormone = somatostatin
5. Prolactin-inhibiting hormone (PIH)
6. Corticotropin-releasing hormone (CRH from paraventricular nucleus)

Tends to tell hormones to do something (aka hormones telling other hormones)

Question 2

What’s the function of TRH?

Answer 2

It stimulates the secretion of thyroid-stimulating hormone in the pituitary gland.

Question 3

What’s the function of GnRH?

Answer 3

Stimulates the secretion of luteinising and follicle-stimulating hormones in the anterior pituitary

Question 4

What’s the function of GHRH?

Answer 4

Stimulates the secretion of growth hormones in the anterior pituitary

Question 5

What’s the function of Somatostatin?

Answer 5

Inhibits the secretion of the growth hormone in the anterior pituitary

Question 6

What’s the function of PIH?

Answer 6

Inhibits the secretion of prolactin in the anterior pituitary

Question 7

What’s the function of CRH?

Answer 7

Stimulates the secretion of the adrenocorticotropic hormone in the anterior pituitary (key for the HPA access)

Question 8

What’s the simplistic process of the HPA axis?

Answer 8

Hypothalamus -> releasing factor –> anterior pituitary -> ACTH (through blood) –> Adrenal cortex -> Cortisol

Question 9

What are the 5 main anterior pituitary hormones?

Answer 9

1. Growth hormone (somatotropin) GH
2. Thyroid stimulating hormone TSH
3. Follicle-stimulating hormone FSH
4. Luteinizing hormone LH

5.Adrenocorticotropic hormone ACTH

These hormones have a more direct effect with actions to the body

Question 10

What is the function of GH?

Answer 10

To stimulate body growth, cell multiplication & differentiation.

Question 11

What is the function of TSH?

Answer 11

To stimulate the secretion of thyroid hormones.

Question 12

What’s the function of FSH?

Answer 12

To stimulate the development of ovarian follicles & spermatogenesis in the testis.

Question 13

What’s the function of LH?

Answer 13

To cause ovulation and stimulate the corpus luteum; to stimulate the secretion of estrogen & progesterone in ovaries; to stimulate testosterone in the testes.

Question 14

What’s the function of ACTH?

Answer 14

To stimulate the secretion of glucocorticoids & androgens in the adrenal cortex.

Question 15

Where is cortisol released?

Answer 15

In the adrenal cortex just at the top of the kidneys (medulla=centre layer + cortex=outer layer)

Question 16

What are the 3 Ways in which HPA Axis Activity is regulated?

Answer 16

1. Diurnal rhythm (our energy is mobilised with sugar entering our body early into the day and decreasing by end of night)
2. Negative feedback
3. Stress

Question 17

Where does cortisol go?

Answer 17

-Almost every cell in the body has cortisol receptors

-Up to 95% of secreted cortisol is bound to large proteins e.g., globulin and albumin) & carried in the body through the blood

-Unbound cortisol can freely enter all tissues, passing through the parotid gland into the saliva and through the kidney into the urine (it goes through so many places)

-Unbound cortisol can cross the blood-brain barrier (this is how we know cortisol affects behaviour including the fact that there are cortisol receptors in areas of the brain)

Question 18

How is the amygdala involved in cortisol?

Answer 18

-Has glucocorticoid receptors

-Acute (1 day) & chronic (10 days) administration of corticosterone caused prolongation of dendrites (makes us more sensitive to receiving info from our neurones=sensitising our emotional response in the amygdala) in the basolateral nucleus of the amygdala in rodents (Mitra & Sapolsky, 2008) (means we know it responds to cortisol)

-Similarly, acute (1 day) & chronic (10 days) immobilisation stress (can’t move) in rats caused an increase in the number of dendritic spines in the basolateral amygdala after 10 days in rodents (Mitra et al., 2005) (has same response as study above)

Question 19

How is the hippocampus involved in cortisol?

Answer 19

-Has glucocorticoid receptors

Glucocorticoids affects the hippocampus in neurotoxic ways (Lupien & McEwen, 1997, McEwen, 1999):
-Decreased neuronal firing
-Further decreases in neuronal excitability later (have a harder time firing)
-Impaired neurogenesis in the dentate gyrus of the hippocampus, which projects to the amygdala
-Loss of neurons, shrinkage of neuronal bodies & retraction of dendrites (these effects are reversible) in CA1-3 regions (key to learning and memory in the hippocampus)

Question 20

What did Uno et al., (1989) find concerning the hippocampus and cortisol in monkeys?

Answer 20

-Suggested there’s a hierarchy with subordinate monkeys and dominant monkeys (looked at the subordinates)

-Neurones had shrunk there was fewer of them

-Concluded this stress was causing the neurotoxicity to the hippocampus

-Also found the adrenal glands were enlarged and were outputting a lot of cortisol (as this is where it’s released)

Question 21

How is the Pre-frontal cortex involved in cortisol?

Answer 21

-Has an abundance of glucocorticoid receptors

-Activity in the ventral medial PFC decreased during acute stress in healthy people, correlating with cortisol increases (Sinha et al., 2016) (concluded cortisol is involved in the decreased activity)

-Daily injections of corticosterone for 3 weeks or 10 min/day stress caused shortening of dendrites in PFC pyramidal neurons in rodents (Brown et al., 2005)

-amygdala=prolonging of dendrites
-hippocampus=neurotoxic effects
-PFC=shortening of dendrites

Question 22

How does cortisol modify behaviour?

Answer 22

-Emotional regulation is impaired (amygdala)

-Complex effects on memory, disrupting memory formation but sharpening memory consolidation and retrieval (hippocampus)

-Cognitive deficits in learning and decision-making & slow extinction of fearful memories (PFC)

-Observed rodents & people after long-term exposure to corticosterone/cortisol & stress, suggesting evolutionary-based functions and processes during stress

Question 23

How does cortisol work in a negative feedback loop?

Answer 23

The hippocampus, amygdala, PFC sends signals back to the hypothalamus e.g., ‘we have enough cortisol you can down-regulate and produce less CRH’

Question 24

What are 4 ways cortisol samples can be collected?

Answer 24

1. Blood
2. Saliva (1 and 2 reflects activity in the past 10-60 minutes)
3. Urine (Reflects activity in the past 24 hours)
4. Hair (reflects activity in the past few months)

Question 25

What are the 5 ways to assess cortisol?

Answer 25

Single sample:
1. Overnight cortisol

Multiple samples:
2. Total cortisol concentration over the day (area under the curve, aka AUC)

3. Diurnal cortisol rhythm
4. Cortisol awakening response (CAR)
5. Cortisol reactivity & recovery

Question 26

What’s overnight cortisol?

Answer 26

-Urine sample

-Provides a measure of non-stimulated level of cortisol activity (aka cortisol NOT in response to a stressor just general levels)

-Greater overnight cortisol is associated with increased mortality risk & declines in cognitive and physical function (Seeman et al., 2001)

Question 27

What’s Total Cortisol Concentration Over the Day (Area Under the Curve, AUC)?

Answer 27

-Saliva or blood samples, < 2 samples per day, < at least 3 days

-Provides a daily measure of cortisol activity with more precision than overnight cortisol

Question 28

What’s the Diurnal Cortisol Rhythm?

Answer 28

-Saliva or blood samples, < 2 samples per day, < a least 3 days

-Provides a measure of changes in cortisol activity throughout the day

Question 29

What did Bower et al., 2005 find with cortisol and fatigue?

Answer 29

-Those without fatigue have cortisol levels decline throughout the day whereas those with fatigue had their levels still elevated during the evening

-Diurnal cortisol rhythm

Question 30

What did Knight et al, 2010 find with cortisol and depression?

Answer 30

-People with depression have blunted levels of cortisol and less of a slope than those without

-Diurnal cortisol rhythm

Question 31

What’s Cortisol Awakening Response (CAR)?

Answer 31

-Saliva or blood samples, < 2 on day, 1 immediately after waking (before getting out of bed), 1 30-45 min post-waking

-Unbound cortisol levels increase by 50-75% within the first 30 minutes post-walking
-“Blunted” or “exaggerated” rise may be associated with psychopathology

Question 32

What did Rohleder et al., 2004 find with cort response and PTSD?

Answer 32

Found blunted cortisol awakening response with people in PTSD

Question 33

What did Adam et al., 2010 find with awakening cort response predicting onset of major depression?

Answer 33

Exaggerated cortisol awakening response in those with depression compared to those without

Question 34

What’s Cortisol Reactivity & Recovery?

Answer 34

-Saliva or blood samples, < 3 on day, 1 pre-stress, 1 20 min post-stress (peak), < 1 15-20 min after peak (to see how someones cortisol levels returns to normal after peak)
-Best to conduct studies in late afternoon to minimise diurnal rhythm influence/have lower baseline

-Cortisol increases in response to certain types of stress

Question 35

What did Dickerson and Kemeny (2004) find with acute stress and cortisol?

Answer 35

-Largest stress with cortisol is public speaking or uncontrollable cognitive task
-Next was public speaking WITHOUT cognitive task

-Uncontrollability and social threat are the biggest stressors eliciting a cortisol response (which aligns evolutionary wise)

-Small gender differences in this study (men took longer to recover from stress)

Question 36

What did Creswell et al., 2005 find with self-affirmation buffering cortisol reactivity to acute stress?

Answer 36

-Blunted reactivity to the stressor if doing self-affirmations (i.e., lowered stress can be regulated with kindness)

Question 37

What did Bower et al., 2005 find with cortisol reactivity and fatigue?

Answer 37

People with fatigue have a lower reactivity response

Question 38

How does a low-dose dexamethasone suppression test inform about the strength of HPA negative feedback?

Answer 38

Dexamethasone (a potent, synthetic glucocorticoid) is applied, & the cortisol level is recorded. If HPA negative feedback works, cortisol levels would decrease

-Poor HPA feedback could be a result of Cushing’s disease or stress as an example

Question 39

What’s the definition of pain?

Answer 39

An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (International Association for the Study of Pain, 1994)

Question 40

What’s Stress-Induced Analgesia?

Answer 40

-Based on the observation on Col. Henry Beecher (1946) on soldiers sustaining major injuries in combat zones of WW2
-73% of wounded soldiers did not require any morphine

-“Stress-induced analgesia is a built-in mammalian pain suppression response that occurs during or following exposure to a fearful or stressful stimulus” (Butler & Finn, 2009)

Question 41

What’s the basic scheme of stress-induced analgesia?

Answer 41

1. Stress
2. Cortisol secretion (through the HPA axis activity)
3. Binds to receptors in the brain
4. Brain regions responding to cortisol stimulate the endogenous opioid system (provides relief from pain)
5. the endogenous opioid system suppresses incoming afferent pain impulses by inhibiting the spinal cord neurons via descending spinal tract

Question 42

What did Van Uum et al., 2008 find with elevated levels of stress & hair cortisol in chronic pain patients?

Answer 42

-Patients with chronic pain are perceiving more stress and have elevated levels of cortisol in their hair

-This shows cortisol activity levels have been high the past month

Question 43

What evidence shows that cortisol levels are often found to be elevated in chronic pain patients?

Answer 43

1. Fibromyalgia syndrome patients (Crofford et al., 2004)
2. Burning mouth syndrome (Amenabar et al., 2008)
3. Temporomandibular disorder (Korszun et al., 2002)