603: Endocrine Final Review I (Bellinger)

ACTH (therefore *cortisol*) Glucocorticoids (cortisol) Mineralcorticoid (aldosterone)

Cushing's disease causes a pathologically high level of _________. This shows how high levels of ________ can have _________ activity.

Causes closure of the epiphyseal growth plate due to *senescence* of *reserve/pre-chondrocytes*

How does estrogen turn off puberty?

Glucose enters down a concentration via a glucose transporter Hexokinase/glucokinase converts it to G6P Too much G6P will have a *negative feedback* on hexokinase/glucokinase to stop the uptake of glucose

How does glucose enter the cell? What occurs with a build up of G6P?

- light inhibits PVN - less AcH - less NE (*less sympathetics*) - *decreased* melatonin release

How does light affect the release of melatonin from the pineal gland?

More ANPR-C = more clearance of ANP Less ANP in the blood = increased blood volume

How would an increase in ANPR-Cs effect blood volume?

Lipoprotein lipase Glucose Glucose is needed to supply *a-glycerol* to make the triglycerides

IGF-I activates a _________ to build fatty acids into triglycerides but also requires the entry of _________ into the cell. Why is this uptake required?

Glucose Non-neural tissues (and some neural) can use *fatty acids*, which get converted to ketone bodies in B-oxidation

In severe caloric restriction, GH helps prevent the uptake of _______, saving it for the brain. What do peripheral tissues use in this case?

GnRH Female adipose mass increases sooner = more leptin = sooner GnRH released - this helps cause earlier trigger of puberty in females

Leptin stimulates the release of ________. How does this affect the timing of puberty?

lightening

Low levels of ACTH would cause skin to....

ACTH This means that a-MSH and ACTH are *structurally similar* AKA: excess ACTH in humans (from destruction of adrenal cortex) can attach to a-MSH receptors —-> Addison's Disease (dark skin)

A-MSH and B-MSH both originate from a pre-pro-opiomelanocortin protein. What other hormone originates from this? What is the significance?

Speed of Action: nervous Distribution: endocrine Selectivity: nervous

Compare the nervous vs endocrine system on these factors. Which is greater for each? Speed of Action Distribution Selectivity

Anterior: - ACTH - TSH - FSH - LH - PRL - GH Posterior: - oxytocin - ADH

Name the hormones of the anterior and posterior pituitary:

Oxytocin

Prior to parturition, the number of ________ receptors is up-regulated.

Glucocorticoids - inhibits proliferation and hypertrophy of growth plate

Prolonged use of _________ in children with asthma can also lead to stunted growth. How does this occur?

GH Cortisol (stress for final right before you wake up Monday morning)

Regarding circadian rhythms, ________ is released right after you fall asleep while __________ is released right before you wake up.

Hypothalamus Oxytocin (paraventricular nucleus) Vasopressin (Supraoptic) Then travel down the hypothalamohypophysial tract

Where are vasopressin (ADH) and oxytocin produced?

IGF-II

Which IGF is only found during fetal development?

Somatotropes (GH) Lactotropes (PRL)

Which cells of the anterior pituitary are acidophils?

Hormone sensitive lipase - allows for release of *free fatty acids* for muscle and other tissue

Which enzyme does epinephrine activate to break down triglycerides?

Aquaporins

ADH increases water reabsorption by adding __________ into the membrane.

Estrogen

According to Dr. Bellinger, what turns puberty on and off?

Arrestin Phosphate

After the enzymatic response, what two substances attach to the GCPR to prevent an immediate second response?

Epinephrine Glucagon CAMP

Although they bind to different receptors, both _______ and ________ lead to an increase in _________, and an increase is glycogenolysis.

Increase Increase Decrease

At the muscle cell, insulin will (increase/decrease) amino acid uptake, (increase/decrease) protein synthesis and (increase/decrease) protein degradation.

CREB (cyclic AMP response element binding protein)

Catalytic Protein Kinase A enters the nucleus and interacts with ________, which causes a gene expression response.

Alpha 1: vasoconstriction Beta 1: vasodilation

How does epinephrine affect a1 versus B2 receptors differently?

- Phospholipase C cleaves PIP2 - IP3 and DAG (DAG is a "dagger" stuck in the membrane) - DAG —-> Protein Kinase C - IP3 —-> release Ca++ from ER

Describe the steps in the second messenger typically seen with *contraction*:

Estrogen Low receptors for estrogen prevents motility of uterine muscle while fetus is growing - estrogen can't reach threshold

During pregnancy, progesterone helps to attenuate the number of _______ receptors. Why is this helpful?

GDP GDP GTP GTP Alpha

During the inactive form of the GCPR, (GDP/GTP) is attached. Once the hormone binds, conformation change occurs to cause _______ to detach _______ to attach to the receptor. ________ remains attached to the _______ unit (typically) and goes on to cause an enzymatic response.

Increased camp = PKA = phosphorylation Phosphorylation will *inactivate* glycogen synthase Phosphorylation will *activate* phosphorylase a (active form)

Explain how glucagon/epi turn enzymes on and off regarding glycogen:

Less cAMP = less PKA = dephosphorylation Dephosphorylation will *activate* glycogen synthase Dephosphorylation will *inactivate* phosphorylase b (Remember - phosphorylase LIKES to be phosphorylated!)

Explain how insulin turns enzymes on/off regarding glycogen:

ATP CAMP Regulatory units Protein Kinase A Catalytic unit (of PKA)

GCPRs can activate Adenyl cyclase to convert _______ to _______. This then attaches to the _______ units of ________ to allow for the release of the ________.

PFK (phosphofructokinase) - does not allow formation of F-1,6-DP; causes build up of G6P - high G6P means inhibition of hexokinse This is what is meant by the "diabetogenic effect" of GH

GH decreases glucose utilization by inhibiting what enzyme?

Stomach (endocrine) Hypothalamus (paracrine) Helps to increase the release of GH

Ghrelin is released from both the _______ and the _________. What does it do?

Increase Decrease *glucagon/epi* leads to phosphorylation

Glucagon/epi (increase/decrease) cAMP while insulin will (increase/decrease) cAMP. Which hormone leads to phosphorylation of glycogen synthase and phosphorylase?

Lipolytic Lipogenic - due to activation of *insulin receptors*

Growth hormone is (lipolytic/lipogenic) while IGF-I is (lipolytic/lipogenic). Why does this occur?

hormone sensitive lipase

Growth hormone stimulates a _________ to break down triglycerides into fatty acids and glycerol.

chondroblast proliferation and hypertrophy

How do GH and IGF-1 affect long bones?

- increase its solubility - serve as a hormone reservoir - protect form degradation (increase half life)

How do binding proteins help IGF?

positive

The Ferguson reflex is a ________ feedback mechanism.

Insulin

The IGF-I receptor is very similar in structure to the ____________ receptor.

5'

The hormone response element is on the ________ side of DNA.

False - short term exercise = more GH - aerobic exercise = less GH True True

True or false (for each statement): Endogenous GH increases during aerobic exercise Most cancers are not affected by growth hormone Normal birth weight is not GH-dependent

True

True or false: Both lack of fetal nutrition or over-feeding after birth can lead to obesity and diabetes

False

True or false: all neurons can use ketone bodies

True However, humans have *alpha MSH receptors*

True or false: alpha and Beta MSH probably have little or no role in humans

True

True or false: because ADH/vasopressin and oxytocin share similar structure, they share, to some degree, biological activity

True

True or false: both milk-let down and production can be stimulated using psychic stimulation

True - but requires GH independent IGF-I and IGF-II

True or false: fetal growth is independent of GH

True

True or false: girls enter puberty sooner so have less time for GH secretion

True Functions: - amino acid uptake - protein formation - decrease protein catabolism - decrease glucose uptake - Lipolysis*

True or false: growth hormone is both anabolic and catabolic

True

True or false: growth is episodic rather than liner

False Malnutrition will *lower IGF-I*, but due no negative feedback, this will *increase GH* However, no IGF I = no growth

True or false: malnutrition will lower IGF-I and growth hormone

False - reported to *decrease* birth weight

True or false: marijuana has been reported to increase birth weight

True

True or false: most receptors are recycled

True Changing needs can override the negative feedback using secretions from the *CNS* EX: - stress induces excess CRH release - cortisol can't keep up as a negative feedback inhibitor of CRH

True or false: negative feedback is a key regulatory function but does not override hormonal needs during stress

False Evidence has shown that *estrogen* among other steroids also have *membrane receptors* —-> allows a faster response

True or false: steroid hormones like estrogen are lipid soluble so only act on receptors within the cytosol or nucleus

True Thirst is only triggered after higher increases is osmolarity. Small changes are controlled by ADH; once above 295, thirst kicks in

True or false: with a slight increase in osmolarity above normal, thirst will not be triggered in the Brian

supersensitivity

Upregulation of receptors, also called _________, as well down regulation, will always *approach* normal hormone activity, but *never fully reach it*.

secreted from ductless gland/neuron/tissue acts at *distant site* -removal causes deficit / return corrects deficit must be a *physiological regulator* *minute amounts* (microgram or less)

What are the key criteria of hormones?

- contraction for fertilization - parturition (increased *oxytocin receptors* and *gap junctions") - milk *let down*

What are the key physiological effects of oxytocin?

- increased GFR - increased renal blood pressure - less renin secretion (more urination) - decreased Na+ reabsorption - decreased angtiotensin II - decreased ADH

What are the physiological effects of ANP? (Alpha ANF)

- amino acid uptake - protein formation - decreased protein degradation - *triglyceride formation* (just like insulin)

What are the primary physiological effects of IGF-1?

Increase blood pressure (V1 receptor) Increase water reabsorption (V2 receptor)

What are the two effects of Vasopressin/ADH? What receptors are involved?

- activate myosin light chain kinase (to phosphorylate myosin) - remove Caldesmon from actin AKA: *two calmodulins* are needed per cycle

What are the two jobs of Ca++ with Calmodulin?

- stimulates somatostatin (less GH) - inhibits GHRH (less GH)

What are the two ways IGF uses negative feedback?

- increased right atria pressure - increased plasma osmolarity (leading to increased volume)

What conditions would cause an increase in aANF? (ANP)

Phosphodiesterase breaks down cAMP NO phosphates are lost in creating 5-AMP (just breaks cyclic form)

What enzyme breaks down cAMP? How many phosphates are lost?

C-fos (think of his study)

What gene can you expect to be made when a cell is activated?

GnRH (every hour) - Ex: artificial ovulation

What hormone follows a circhoral release?

A carrier molecule synthesized with the hormones NPI = Oxytocin NP2 = Vasopressin

What is Neurophysin?

Short loop: - a hormone prevents its OWN release EX: ACTH feeds back to anterior pituitary to prevent its own release Long loop: - hormone prevents a step above its own release in the chain

What is an example of short loop feedback? How does this compare to long loop?

GH at the tissues produces IGF-1 In the *tissues* (not the liver), this IGF-1 can sometimes do an autocrine/paracrine effect as well AKA: tissue IGF-1 is *free*, while liver IGF-1 is *protein bound*

What is meant by "dual effect" of GH and IGF-1 at the tissues?

Can release pro-inflammatory cytokines Decrease GH signaling = less growth

What is the affect of endotoxins on growth?

In case only water or only salt is in abnormal concentration

What is the benefit of having separate volume and osmolarity receptors?

Both transform glucose into G6P to lock it into the cell but *muscle only has hexokinase*

What is the difference between Glucokinase and hexokinase?

Both describe G-coupled protein receptors: Gs = stimulatory Gi = inhibitory

What is the difference between a Gs and Gi?

Paracrine: neighbor cell Intracrine: inside cell to another part of the cell Juxtacrine: portions of molecule attached to outside of cell Parahormone: released by everything (Glucose, O2, CO2, Ca++)

What is the difference between these? Paracrine Intracrine Juxtacrine Parahormone

Helps to inhibit GH by *activating the inhibitory hormone somatostatin*

What is the feedback role of IGF-1?

STAT

What is the name of the transcription factor for growth hormone?

285

What is the normal value for plasma osmolarity (according to Bellinger)?

- acute hypoglycemia - starvation - high protein meal (with AA)

What metabolic states will cause an increase in GH?

Activates glucokinase (More glucose uptake) Inhibits G6-phosphatase (Less glycogen breakdown)

What primary enzymes are activated and inhibited by insulin?

PIP2 / IP3 and DAG - on alpha receptors contraction occurs with sympathetics

What second messenger system is used with epinephrine and norepinephrine on alpha receptors?

- clearance receptors - destructive proteases

What two substances help to break down ANP?

Intracellular catalytic domain (tyrosine kinase)

What type of receptor is used with insulin?

By platelets during injury - high activity of IGF-1 as it is not bound to carriers

When can IGF-1 be released without growth hormone?

Adenyl cyclase ATP to CAMP *Relaxation*

When epinephrine contacts Beta receptors of vascular smooth muscle cells, what secondary messenger system is activated?

ADH Higher levels of ADH will cause excess water retention and low urination —-> this why surgery patients are given fluid and urine is monitored

Which hormone can be increased during stressful situations like surgery? Why is this important to consider?

Growth hormone (every few hours) - this is why you need to test for GH levels every 15 minutes

Which hormone follows an ultradian rhythm?

GnRH - releases FSH and LH

Which is the only releasing hormone to cause the release of two different pituitary hormones?

C-peptide

Which part of pro-insulin is not seen in the complete insulin hormone?

Activates G6-phosphatase (More glycogen breakdown) Inhibits glucokinase (Less glucose uptake)

Which primary enzymes are activated and inhibited by glucagon?

Glucagon Epinephrine

Which two hormones promote the breakdown of glycogen?

To guarantee the hormone contacts the receptor Note: - full activation of insulin only requires *2%* receptor activation

Why do our cells have SO many extra insulin receptors?

Different cells have different *receptor majority* Remember: alpha and Beta receptors are on all smooth muscle; but the majority receptor will win Ex: skin is manly alpha, skeletal muscle is mainly Beta 2

Why doesn't epinephrine cause contraction and relaxation simultaneously on smooth muscle cells?

Shrink (depolarize)

With increasing plasma osmolarity, osmotic receptors (shrink/swell).

Epinephrine Norepinephrine (Ex: contraction with alpha receptors)

_______ and ________ have the same receptor and the same Gs response.

Prolactin

________ is a unique hormone because its release is primarily controlled by an inhibitory hormone.

GHRH Positive: - Ghrelin Negative: - Somatostatin - IGF-1

__________ causes the release of growth hormone. Which hormones have a positive/negative affect on the release of GH?