Lecture 1

Question 1

What are the three properties of classic endocrine glands? What are some classic endocrine glands?

Answer 1

1. ductless
2. secrete hormones directly into the bloodstream or extracellular space
3. the entire organ is dedicated primarily to endocrine function
   - pineal gland(sits on top of epithalamus-outside BBB)
   - pituitary gland-hangs below brain
   - parathyroid gland
   - thyroid gland
   - adrenal gland
   - pancreas
   - ovary
   - placenta
   - testis

Question 2

What are the 6 non-classical endocrine organs?

Answer 2

brain-especially hypothalamus (“releasing hormones”)
kidney-vitamin D
heart- anp, bnp
liver-insulin-like growth factor
GI-small intestine, stomach (serotonin, ghrelin)
Adipose tissue-liptin

Question 3

What is homeostasis?

Answer 3

the state of equilibrium in the body with respect to various functions and to the chemical compositions of the fluids and tissues

Question 4

hyper

Answer 4

over production of a hormone and or hypersensitivity to hormonal effects

Question 5

hypo

Answer 5

underproduction of a hormone and or insensitivity to hormonal effects

Question 6

What organ will all of the hormones from the different systems effect?

Answer 6

thymus

• stomach–>+ghrelin
• adipose–>+leptin
• thyroid gland–>+thyroid hormone
• adrenal glands–> - adrenaline, cortisol
• brain—>+ GH, GnRH
• gonads–> - testosterone

Question 7

What are endocrine pathologies characterized by? What would be a primary defect vs a tertiary or secondary defect?

Answer 7

characterized by a hormone imbalance

• primary defect: defect in classical endocrine gland(adrenal)
• secondary/ tertiary defect: defect in other organ

Question 8

Cretinism
Etiology
Deficiency
Effect

Answer 8

• Congenital
• Iodine deficiency during development
• short stature/impaired bone formation
• mental retardation
• delayed motor development

Question 9

Multiple Endocrine Neoplasia (MEN)
Etiology
Description

Answer 9

Genetic

Characterized by 2-3 tumors in multiple endocrine glands
parathyroid, pituitary, entero-pancreatic

Question 10

What are 2 examples Malignant and benign tumors that can cause endocrine pathologies?

Answer 10

neoplastic tissues

small lung cell carcinoma–>secretes high levels of a hormone (not in endocrine gland)

Question 11

What is a type of immunological problem that can cause endocrine pathologies?

Answer 11

Autoimmune-Diabetes Mellitus Types 1

Question 12

What are some environmental factors that are endocrine disruptors?

Answer 12

PCBs(used in electrical equipment), DES(synthetic estrogen), Birth Control

Question 13

What is a syndrome caused by trauma/stress that causes endocrine pathology?

Answer 13

Sheehan’s syndrome-postpartum hemorrhage/shock; results in massive pituitary cell death

Question 14

What surgical procedure could cause endocrine pathology?

Answer 14

Thyroid gland removal (often parathyroid injury)

Question 15

What therapy could cause endocrine pathology?

Answer 15

glucocorticoid therapy (crohn’s disease and others)

Question 16

What is the most common endocrine pathology?

Answer 16

Diabetes mellitus type 2

• affect 9.3% of the pop
• 7th leading cause of death
• usually develops over long period of time
• highly correlated with obesity
• 27.8% of people with diabetes are undiagnosed

Question 17

How many children in the US are overweight or obese?

Answer 17

over 1/3

Question 18

Endocrine vs. paracrine vs. autocine

Answer 18

endocrine-hormones secreted into the blood acting on downstream target tissues
paracrine-hormones secreted into interstitial space acting on nearby cells (neuron)
autocrine-hormones secreted into the interstitial space acting back on same cell

Question 19

What do hormone binding proteins do? What are they mostly used for?

Answer 19

Bind to hormones in the blood to facilitate transport
Generally increases the half-life of the hormone
(hormone does not have action when it is bound)

Mostly for steroid hormones (lipophilic)
-Also: IGF-I, GH, T4/T3

Question 20

What does sex hormone binding globulin (SHBG) bind?

Answer 20

estrogen and testosterone

Question 21

What does corticosteriod binding globulin (CBG) bind?

Answer 21

cortisol/corticosterone

Question 22

What does thyroxine binding globulin (TBG) and transthyretin (TTR) bind?

Answer 22

thyroid hormone

Question 23

What is the non specific hormone binding protein that transfers most lipophilic compounds in the blood?

Answer 23

albumin

Question 24

Does albumin need an enzyme to remove the hormone from the hormone binding protein?

Answer 24

No-its a weak interaction

but most other do-other are so specific that they tend to bind up all hormones that are in circulation

Question 25

Is albumin bound hormone bioavailable?

Answer 25

yes

Question 26

What are 2 ways bound hormones are delivered to target cells?

Answer 26

1. steroid hormone is released at membrane-->freely diffuses across lipid bilayer-->finds intracellular targets 2. hormone/protein complex binds to megalin-->formation of endocytic vesicle--->hormone dissociates and is released from vesicle

Question 27

What determines the duration of hormone activity?

Answer 27

Receptors cell surface receptors=internalized/dissociation intracellular receptors=ubiquitination

Question 28

Can receptors autoregulate by ligand depending on hormone levels?

Answer 28

Yes

Question 29

What is specificity?

Answer 29

ability to distinguish between similar substances

Question 30

What is affinity measured as and what does it represent?

Answer 30

measured as Kd | =ligand concentration that occupies 50% of binding sites

Question 31

What is Ki?

Answer 31

Ability to displace ligand at 50% of maximum activity | -smaller number=higher affinity

Question 32

When there is a shift to the right in a competition binding assay specificity what does that mean ?

Answer 32

Need much more of those other hormones to kick off the main hormone

Question 33

What are the 4 types of lipophobic receptors?

Answer 33

Ion Channels G protein coupled Receptor linked kinases Receptor kinases

Question 34

How do ion channels work?

Answer 34

ligand binding causes conformational change that opens channel Neurotransmitters typically activate these types of receptors

Question 35

How do G-coupled protein work?

Answer 35

ligand binding activates second messenger signaling cascade *Most proteins and peptide hormones bind this class of receptor

Question 36

How do receptor linked kinases work?

Answer 36

Don't have intrinsic catalytic activity -ligand binding causes dimer formation-activates intracellular kinase Examples: growth hormone, prolactin, erythropoietin

Question 37

How do ion channels work?

Answer 37

ligand binding causes conformational change that opens channel -activation of conductance Neurotransmitters typically activate these types of receptors

Question 38

How do G-coupled protein work?

Answer 38

ligand binding activates second messenger signaling cascade - generation of second messenger - activation of cell signaling * Most proteins and peptide hormones bind this class of receptor

Question 39

How do receptor kinases work

Answer 39

Have intrinsic catalytic activity that is stimulated by ligand binding - phosphorylation of tyrosines on key signaling molecules - activation of cell signaling Examples: insulin and ANP

Question 40

How do lipophilic hormone receptors work?

Answer 40

1. bind mainly to intracellular receptors 2. often bound to large chaperone proteins in cytoplasm (heat shock) 3. usually slow biological response-requires transcription/translation events 4. can repress or activate transcription

Question 41

How does thyroid hormone work?

Answer 41

1. binds nuclear receptors 2. ligand binding activates gene transcription (when not bound to ligand=transcriptional repression)

Question 42

What affects hormone bioavailability?

Answer 42

1. hormone transport (free vs. bound & half life) 2. target tissue (receptors, chaperones) 3. Hormone synthesis/ release (enzymatic activity and processing/packaging) 4. Regulatory mechanisms (feedback, circadian rhythms, aging, pulsatility, metabolism/degradation)