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Endocrinology Lecture 18: Adrenal Lecture

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What is the effect of stress on the body?
The brain becomes more alert, heart rate increases, digestive rate decreases, adrenal glands produce adrenal hormones
What is an adrenal stress hormone?
Cortisol is an adrenal stress hormone that increases abdominal fat and glucose production
What is the metabolic syndrome?
Metabolic syndrome is insulin resistance, visceral obesity, and sarcopenia caused by chronic stress
What is the stress system?
The stress system follows the HPA axis: hypothalamus releasing corticoreleasing hormone which stimulates the Pituitary which releases adrenocorticotrophic hormone which stimulates the adrenal cortex which makes cortisol and adrenaline
Where does the medulla develop from?
The Adrenal medulla develops from neural crest ectoderm
Where does the cortex develop from?
The adrenal cortex develops from mesoderm
What is bigger in a newborn, the adrenal medulla or adrenal cortex?
The adrenal cortex
what is bigger in an adult, the adrenal medulla or adrenal cortex?
The adrenal medulla
Glucocorticoids of the adrenal cortex are made in what zone?
Zona fasciculata and secondarily the zona reticularis
What are the functions of cortisol?
Cortisol stimulates glucose formation, promotes fatty acid release, inhibits protein synthesis and inhibits secretion of CRH and ACTH
What is the neurohypothalamic pathway stimulated by stress?
Stress signal to the cerebral cortex stimulates the visceral brain which stimulates the sympathetic nervous system which stimulates the adrenal medulla which releases epinephrineleading to acute stress
What is the endocrine hypothalamic pathway stimulated by stress?
Stress signal to the cerebral cortex stimulates the visceral brain which stimulates the endocrine hypothalamus to release CRH which stimulates the anterior pituitary to release ACTH which stimulates the adrenal cortex to release cortisol which is a chronic stress response. It also increases the level of beta endorphine
What is 11 beta hydroxysteroid dehydrogenase?
11 beta hydroxysteroid dehydrogenase or HSD11 is the enzyme that inactivates cortisol by converting it to cortisone
How is cortisol excreted?
The liver adds a hydroxyl group in the 17 position of cortisol producing a 17-hydroxysteroid which is inactive and water soluble. Excreted via kidneys
What acts contrarily to cortisol?
Epinephrine and glucagon act contrarily to cortisol by inhibiting glycogenesis and increasing glycogenolysis
How does cortisol affect muscle?
Cortisol inhibits muscle uptake of blood glucose, increases protein breakdown resulting in more amino acids
How does cortisol affect fat cells?
Cortisol inhibits glucose uptake by fat cells and increases fatty acid breakdown resulting in more free fatty acids
How does cortisol affect the liver?
cortisol increases gluconeogenesis and subsequently glycogenesis
What are the proinflammatory cytokines?
IL1, IL2, IL6, IL12, TNF-alpha, TNf-gamma
What are the antiinflammatory cytokines?
IL4. IL10
How do glucocorticoids impact prostaglandin production?
Prostaglandins are produced from arachidonic acid which is produced from phospholipids by phospholipase A. Glucocorticoids inhibit phospholipase A.
How does aspirin impact prostaglandin production?
Aspirin blocks cyclooxygenase which converts arachidonic acid to prostaglandins
What is COX-1?
COX-1 is cyclooxygenase 1, expressed in most tissues, produces prostaglandins that affect platelet aggregation, renal function, vascular homeostasis
What is COX-2?
COX-2 is cyclooxygenase 2, expressed in cells involved in inflammation. Induced in response to cytokines, inhibited by glucocorticoids
How does fetal cortisol affect the mother after childbirth?
Increasing fetal cortisol increases mother's estrogen during last weeks of pregnancy increasing oxytocin receptors and decreasing progesterone causing myometrial weakness and irritability.
How does cortisol impact prolactin?
Cortisol increases prolactin receptor synthesis and increases transcription/translation of prolactin
What is Cushing's Syndrome?
Cushing's syndrome is hypercortisolism from pituitary or adrenal tumors
What is addison's disease?
Addison's disease is hypocortisolism
What is Acute Depression in terms of cortisol?
Acute depression is an increased state of all HPA axis hormones (CRH, ACTH, Cortisol)
What is chronic depression in terms of cortisol?
Chronic depression is an increase in CRH but not ACTH
What are the four neurotransmitters underlying depressive disorders?
Norepinephrine, Serotonin, Acetylcholine, Dopamine
What is BDNF?
BDNF is brain derived neurotrophic factor which acts in the CNS and PNS and helps support survival of existing neurons. Stress causes a decrease in BDNF Antidepressants increase BDNF
In primary Addisons, CRH and ACTH levels are...
CRH and ACTH levels are elevated, cortisol levels are low
What are 8 things that stimulate the catecholaminergic pathway?
anxiety, trauma, pain, exercise, hypoglycemia, hypothermia, hypovolemia, and hypoxia
What are the two sympathetic nerve pathways stimulated in the catecholaminergic pathway?
The catecholaminergic pathway stimulates the sympathetic nervous system to release acetylcholine onto sympathetic ganglion which release norepinephrine. Sympathetic nervous system also stimulates the adrenal medulla to produce epinephrine
What is the Locus Ceruleus?
The Locus Ceruleus is a portion of the brain that releases norepinephrine
What is the amygdala?
the amygdala is a portion of the brain that mediates the execution of the stress response
The chromaffin cells of the adrenal medulla are innervated by...
The chromaffin cells of the adrenal medulla are innervated by preganglionic cholinergic neurons.The acetylcholine changes the membrane voltage opening voltage gated calcium channels
Describe the synthesis of dopamine, norepinephrine, and epinephrine from tyrosine
Tyrosine is hydroxylated to L-Dopa by tyrosine hydroxylase. This is the rate determining step. L-Dopa is decarboxylated to Dopamine by L-amino acid decarboxylase. Dopamine is transported into vesicles where it is hydroxylatd to Norepinephrine by dopamine beta hydroxylase. Norepinephrine is methylated to epinephrine by phentolamine N-methyltransferase (PNMT)
Where is norepinephrine made?
Norepinephrine is made in postganglionic sympathetic neurons, CNS, and adrenal medulla. NE binds alpha1, alpha2, and beta 1 receptors
Where is epinephrine made?
Epinephrine is made in adrenal medulla and CNS. Binds alpha 1, alpha2, beta1, and beta 2 receptors
Where is dopamine made?
Dopamine is made in the autonomic ganglia, CNS, adrenal medulla. Binds to Dopamine receptor, alpha1 and beta1 receptors
What does norepinephrine inhibit?
Norepinephrine inhibits tyrosine hydroxylase, acting as a negative feedback.
What is Reserpine?
Reserpine blocks transport of dopamine and NE into vesicles
What influences expression of tyrosine hydroxylase?
Tyrosine hydroxylase TH is influenced by the activity of the preganglionic neuron, known as trans-synaptic regulation
What causes acute secretion of catecholamines?
Acetylcholine increases internal calcium leading to a release of catecholamines, this is acute secretion
What causes chronic secretion of catecholamines?
Glucocorticoids increase synthesis of PNMT in adrenal medulla which increases epinephrine formation
What metabolizes catecholamines?
Catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO)
Epinephrine and Norepinephrine are metabolized to what?
COMT and MAO metabolize epinephrine and norepinephrine to vanillylmandelic acid
Dopamine is metabolized to what?
COMT and MAO metabolize dopamine to homovanillic acid
What are 4 effects of catecholamines on metabolism
Catecholamines increase glucose synthesis, inhibit glucose utilization, inhibit insulin secretion, and stimulate lipolysis and ketogenesis
What are the 3 effects of catecholamines on cardiovascular system?
Catecholamines increase heart rate and contractility, increasing cardiac output and blood pressure. They constrict blood vessels int he GI, kidney and skin. They increase blood flow to muscle, heart, and brain
What do beta adrenergic receptors do?
Beta adrenergic receptors act via Gs proteins to stimulate adenylyl cyclase which increases the rate of glycogenolysis in the liver and lipolysis in adipocytes. Beta adrenergic receptors also cause relaxation of blood vesselsand smooth muscle
What kind of receptor is alpha 1?
Alpha 1 acts through a PLC-IP3-DAG pathway to increase intracellular Ca2+
What kind of receptor is alpha 2?
Alpha 2 acts through a G inhibitor protein that inhibits adenylate cyclase. Norepinephrine binds to Alpha 2 more than epinephrine
What is propanolol?
Propanolol binds to beta adrenergic receptors as an antagonist to epinephrine thus preventing myocardial contraction
What are the 6 methods of beta adrenergic receptor turnoff?
1. dissociation of epinephrine 2. degradation of epinephrine to vanillylmandelic acid 3. receptor phosphorylated by bARK decreases activity of receptor 4. binding of beta arrestin 5. GTPase 6. phosphodiesterase of cAMP to AMP
What are the interactions of catecholamines with other hormones?
1. Catecholamines increase renin release from kidneys 2. catecholamines increase thyroid hormone secretion 3. estrogen increases production of alpha receptors in the uterine 4. adrenergic hormones block effects of insulin
What is a phaeochromocytoma?
A phaeochromocytoma is a tumor of the chromaffin cells of the adrenal medulla resulting in high levels of E and NE and hyperglycemia
What is NE affect on amygdala?
NE from the locus ceruleus causes long term potentiation of amygdala on traumatic memories
What are MAOIs?
MAOIs are monoamine oxydase inhibitors which block MAO from degrading epinephrine and norepinephrine and dopamine