Endocrine #2

Question 1

Osteoblasts

Answer 1

Bone generating cells

Question 2

Osteocytes

Answer 2

Mature bone cells
Spider shaped
Maintain bone tissue

Question 3

Osteoclasts

Answer 3

Bone destroying cells

Question 4

Bone formation

Answer 4

The process by which osteoblasts synthesize bone

Osteoblasts function in groups of connected cells

Question 5

Osteons

Answer 5

Group of organized osteoblasts together that make bone

Individual osteoblasts cannot synthesize bone by themselves

Question 6

Bone resorption

Answer 6

The process by which osteoclasts break down bone and release the minerals, resulting in a transfer of calcium from bone fluid to the blood

Question 7

Bone homeostasis

Answer 7

The balance between bone formation and bone resorption

Question 8

If the body is low on Ca, what occurs?

Answer 8

Parathyroid hormone (PTH) will be released and

1) bone resorption will increase
2) Ca elimination by the kidney will decrease
3) Ca absorption increases in the gut

Question 9

Parathyroid hormone

Answer 9

88 aa protein, only the first 34 are required for activity

T1/2 in plasma ~4 minutes

Question 10

What are the parathyroid receptors?

Answer 10

PTHR1

PTHR2

Question 11

PTHR1

Answer 11

Located in bone and kidneys
Activation leads to expression of RANK ligand (RANKL) - leading to bingin and activation of osteoclasts and bone resorption

Question 12

PTHR2

Answer 12

Located in CNS, pancreas, testis, placenta

Question 13

What effects does PTH have on the kidney?

Answer 13

Maximize Ca resorption
Decrease PO4 resorption
Enhance vitamin D production

Question 14

PTH effect on vitamin D

Answer 14

PTH enhances the production of calcitrol (active form of vitamin D)
This enhances the absorption of Ca from the gut

Question 15

Calcitrol

Answer 15

Plays a complex role in the Ca homeostasis

• Increases Ca absorption in the gut (main one)
• decrease Ca excretion in kidney
• increase bone resorption and mineralization
• increase osteoclasts development
• decrease PTH secretion

Question 16

T/F - Vitamin D is only related to Calcium

Answer 16

False - Most cells have vitamin D receptors

There are hundreds of vitamin D responsive genes

Question 17

Calcitonin

Answer 17

Released by parafollicular cells of the thyroid in response to high serum Ca concentrations
Counteracts the effect of PTH

Question 18

What are the effects of Calcitonin

Answer 18

Increases bone formation
Decreased kidney resorption of Ca
Decreases Ca absorption by the gut

Question 19

Bisphosphonates

Answer 19

A class of drugs that prevent the loss of bone mass
Used to treat osteoporosis and similar diseases
Most commonly prescribed drugs to treat osteoporosis

Question 20

Bisphosphate effects

Answer 20

Inhibit bone resorption and osteoclast activity
Restore bone density
Mechanism is not totally understood

Question 21

Where do androgens (Testosterone) come from?

Answer 21

95% come form Leydig cells of the tests (some come from ovary)
5% from the adrenal gland

Question 22

What stimulates testosterone synthesis and release?

Answer 22

LH

Question 23

Theraputic use of Androgen

Answer 23

Androgen deficiency (low T, etc)

Question 24

What are the major types of Estrogen?

Answer 24

Estradiol (E2)
Estrone (E1)
Estriol (E3)

Question 25

Estradiol (E2)

Answer 25

Major secretory product of ovary

Question 26

Estrone (E1) and Estriol (E3)

Answer 26

Made in liver from estradiol

Question 27

Natrual estrogens

Answer 27

From which synthetic estrogens were derived (estradiol, estrone, estriol)

Question 28

Synthetic estrogens

Answer 28

Most commonly used in oral contraceptives

Question 29

Synthetic nonsteroidal compounds with estrogenic activity

Answer 29

Have also been used clinically

Question 30

What are the major clinical uses of Estrogen?

Answer 30

Primary hypogonadism Postmenopausal hormonal therapy Other uses

Question 31

How is estrogen used to help treat hypogonadism

Answer 31

For replacement therapy in estrogen-deficiencies due to underdeveloped ovaries, premature menopause, castration, or menopause Attempts to mimic physiology of puberty

Question 32

How is estrogen used to help treat postmenopausal hormonal therapy

Answer 32

Prevent hot flashes and osteoporosis | Use only the lowest possible doses because of increased risks for breast and endometrial cancer

Question 33

Estrogen receptor and treatment of breast cancer

Answer 33

If the breast cancer cells are estrogen receptor positive, estrogen is likely to be driving cell proliferation The drug tamoxifen antagonizes the effect of estrogens in breast cancer cells and blocks proliferation

Question 34

Class 1 Nuclear Receptor Molecular Biology

Answer 34

1) Binding of agonists (eg estradiol to estrogen receptor) produces a conformational change that exposes AF-2 region of the receptor 2) Co-activator proteins such as SRC-1 can only bind to the receptor if AF-2 is exposed. Thus, the co-activators only bind to the receptor if agonist is bound 3) Antagonists bind perfectly well to the receptor, but their binding does not lead to exposure of AT-2. Therefore, the antagonist receptor binds to the DNA, but does not bind co-activators, and the antagonist does not activate transcription

Question 35

Tamoxifen

Answer 35

It's a SERM (selective estrogen receptor modultor) Acts as an antagonist in some tissues but acts as an agonist in other tissues It is speculated that things like availability of co-activators determines if it acts as an agonist or antagonist

Question 36

Where are progestins synthesized?

Answer 36

Corpus luteum Placenta Adrenal cortex

Question 37

Progestins are the precursors to what?

Answer 37

Androgens Estrogens Adrenocortical hormones

Question 38

Progestins play a biological role in what?

Answer 38

Menstrual cycle and pregnancy side note: males have progesterone receptors too, but it's not tremendously understood what effects they have on male sexuality

Question 39

What is required during menstrual cycle for follicle development, ovulation, and pregnancy?

Answer 39

Coordinated pattern of FSH and LH secretion

Question 40

What are the clinical uses of Progesterone?

Answer 40

``` Hormonal replacement therapy Contraception Diagnosis: estrogen secretion Dysmenorrhea Endometriosis ```

Question 41

What effect do Estrogen + Progesterone oral contraceptives have?

Answer 41

Block LH and FSH release from the pituitary

Question 42

What effect do Progesterone oral contraceptives have?

Answer 42

Thickening of cervical mucus (blocks sperm from contacting egg) Block release of eggs from the ovary

Question 43

What are the types of emergency oral contraceptive pills?

Answer 43

1) Higher doses of progesterone alone, or progesterone plus estrogen 2) RU486 (mifepristone) - a low efficacy progesterone partial antagonist - lower dose: emergency oral contraceptive - higher dose: abortifacient (first several months)