71 - Basics

Question 1

What are the 3 major characteristics of a “classic” endocrine gland?

Answer 1

• Ductless
• Secrete hormones directly into the bloodstream or extracellular space
• The organ is dedicated primarily to endocrine function

Question 2

What are some e.g.’s of non-classical endocrine organs?

Answer 2

• Brain (hypothalamus especially)
• Kidney (renin, vit. D, EPO)
• Heart (ANP, BNP)
• Liver (IGF-1)
• GI: stomach/small intestine (5-HT, ghrelin)
• Adipose tissue (leptin)

Question 3

Define homeostasis as it relates to the endocrine system.

Answer 3

The state of equilibrium (balance between opposing measures) in the body w/r/t various functions and to the chemical compositions of the fluids and tissues

Question 4

In endocrine homeostasis, discuss the concept of “hyper”.

Answer 4

Overproduction of a hormone and/or hypersensitivity to its hormonal affects.

Question 5

In endocrine homeostasis, discuss the concept of “hypo”.

Answer 5

Underproduction of a hormone and/or insensitivity to its hormonal affects.

Question 6

In endocrine pathology, primary defects affect a ____________ endocrine gland.

Answer 6

Classical

Question 7

If an endocrine pathology doesn’t affect a classical gland, it’s either a ________ or _______ defect.

Answer 7

Secondary or teritary

Question 8

What’s the etiological category of cretinism?

iodine deficiency, most common cause of retardation world-wide

Answer 8

Congenital

Question 9

What’s the different b/w congenital and genetic?

Answer 9

Congenital: present at birth; not necessarily genetic

Question 10

What’s the etiological category of multiple endocrine neoplasia (MEN)?

(multiple endocrine glands have tumors)

Answer 10

Genetic

Question 11

What’s the etiological category of environmental factors such as PCBs, DES, and/or BCP?

Answer 11

Endocrine disruptors

Question 12

What’s the etiological category of Sheehan’s syndrome?

postpartum hemorrhage/shock; results in massive pituitary cell death

Answer 12

Trauma/stress

Question 13

What’s the etiological category of thyroidectomy?

Answer 13

Surgical

Question 14

What’s the etiological category of glucocorticoid therapy?

e.g. Chrohn’s disease, etc.

Answer 14

Therapeutic

Question 15

What’s the etiological category of neoplastic tumors or small lung cell carcinoma?

(SCLC: cancer not in an endocrine gland, but secretes hormones typically released by the pituitary)

Answer 15

Malignant and benign tumors

Question 16

What’s the etiological category of T1DM?

Answer 16

Infections/immunological problems (Autoimmune, in T1DM)

Question 17

Distinguish amongst endocrine, paracrine, and autocrine.

Answer 17

• Endo: hormones secreted into blood, act on downstream targets
• Para: hormones secreted into ISF, act on nearby cells
• Auto: hormones secreted into ISF, act back on same cell

Question 18

Neurotransmission is a type of (endo/para/auto-crine) signaling.

Answer 18

Paracrine

Question 19

Endo vs. paracrine:

1. Which signaling has more specificity of target?
2. Which has a greater importance on receptors for specificity?
3. Which must be released in greater concentration?

Answer 19

1. Paracrine
2. Endocrine (travels farther)
3. Endocrine (gets diluted)

Question 20

Which are biologically active: free hormones, bound hormones, or both?

Answer 20

Free hormones only

Question 21

What major class of hormones uses binding proteins most often for xport?

Answer 21

Steroid hormones (lipophilic)

Question 22

Do binding proteins change the 1/2-life of their bound hormone?

Answer 22

Yes, increase 1/2-life

Question 23

What’s the major nonspecific binding protein?

Answer 23

Albumin

Question 24

What’s the binding protein for estrogens and testosterone?

Answer 24

Sex hormone binding globulin (SHBG)

Question 25

What's the binding protein for cortisol and corticosterone?

Answer 25

Corticotrophin binding globulin (CBG)

Question 26

What are the 2 binding proteins for TH?

Answer 26

- Thyroid binding globulin (TBG) | - Transthyretin (TTR)

Question 27

Is most hormone in the blood bound or unbound?

Answer 27

Almost all bound

Question 28

When hormones are bound to albumin they're not considered bioactive but they are considered bio-___________.

Answer 28

available (pretty to use hormone bound to albumin if you need to)

Question 29

What are the 3 steps of the old model for hormone delivery to target cell? (just read)

Answer 29

1. Steroid hormone released at membrane 2. Freely diffuses across lipid bilayer 3. Finds extracellular target

Question 30

*What are the 3 steps of the new model for hormone delivery to target cell?

Answer 30

1. Hormone/protein complex binds to megalin 2. Formation of endocytic vesicle 3. Hormone dissociates and is released from vesicle

Question 31

According to wikipedia, what are the effects of ubiquitination?

Answer 31

- Can signal for ptn degradation via the proteasome - Can alter ptn cellular location - Can affect ptn activity - Can promote or prevent protein interactions

Question 32

*What are 3 major categories by which a protein receptor can be regulated? (just read at first)

Answer 32

1. Agonists/antagonists 2. Affect hormone duration: internalization/dissociation/ubiquitination 3. Ligand (hormone) autoregulation

Question 33

Hormones bind receptors w/____ specificity and ____ affinity.

Answer 33

High, high

Question 34

Define specificity.

Answer 34

Ability to distinguish b/w similar substances

Question 35

``` Define Kd (same as Km). What is the relationship b/w Kd and affinity? ```

Answer 35

Ligand conc. that occupies 50% of the binding sites | - Inverse relationship w/affinity

Question 36

Define Ki.

Answer 36

Ability to displace ligand at 50% of maximum activity | - How much of something else do I need to add before I can knock it off?

Question 37

*What are the characteristics of lipoPHOBIC hormone receptors?

Answer 37

- Bind to cell surface receptors - Coupled to 2nd messenger signaling pw's including: cAMP, IP3/DAG - Rapid internalization or degradation

Question 38

*What are 3 eg's of lipophobic hormone receptor classes?

Answer 38

- GPCRs (most) - Receptor-linked kinases = GH, PRL, EPO. - Receptor kinases = insulin, ANP

Question 39

*What are the characteristics of lipoPHILIC hormone receptors?

Answer 39

- Bind mainly to intracellular receptors (some exceptions). - Often bound to large chaperone proteins in cytoplasm (often heat shock proteins) - Usually SLOW biological response – requires TS/TL events. - Can repress or activate transcription.

Question 40

*Does TH bind a lipophilic or lipophobic receptor? | Discuss its somewhat unique properties.

Answer 40

Lipophobic - THs bind nuclear steroid receptors (superfamily even tho they're not steroid hormones) - When receptor is NOT bound to ligand = transcriptional repression. Ligand (TH) binding activates gene TH.

Question 41

What type of cell surface receptors do peptide/protein hormones typically bind?

Answer 41

GPCR (activate 2nd msger)

Question 42

How does a Receptor-Linked Kinase hormone receptor function? | Do they have intrinsic catalytic activity?

Answer 42

Ligand binding causes dimer formation – activates intracellular kinase - DO NOT have intrinsic catalytic activity (GH, PRL, EPO)

Question 43

Do Receptor Kinases have intrinsic catalytic activity?

Answer 43

Yes | Insulin, ANP

Question 44

Factors affecting hormone bioavailability? (read)

Answer 44

Hormone Transport: - Binding proteins – “free” vs bound - Kinetics: half-life Target Tissues: - Receptors – mutations, desensitization, down/upregulation, - Chaperone/Heat shock proteins Hormone synthesis/release: - Enzymatic activity - Processing/Packaging Regulatory mechanisms: - Feedback - Circadian rhythms - Aging - Pulsatility - Metabolism/Degradation