Block 3: Adrogens/estrogens

Front 1

Major sites of androgen synthesis

Back 1

Adrenal cortex (zona reticularis)

Gonads (Testes)

Front 2

Where is the major site of production in women? men?

Back 2

Adrenal gland

Testes

Front 3

What is androgen production controlled by?

Back 3

ACTH

Front 4

What are steroids synthesized from?

Back 4

cholesterol

Front 5

Which androgen does the adrenal produce most.

Back 5

Dehydroepiandrosterone (DHEA)

Front 6

What other minor products does the adrenal make.

Back 6

Androstenedione
Androstenediol
Testosterone

Front 7

What controls production of testosterone?

Back 7

GnRH--LH--Leydig cells--Testosterone

Front 8

What androgens are produced in the testes?

Back 8

Testosterone
Dihydrotestosterone (DHT)
DHEA (minor)
Androstenedione

Front 9

What transports androgens?

Back 9

Testosterone-estrogen binding protein (30%)

Albumin (68%)

Free (2%)

Front 10

What is the active fraction?

Back 10

AF = free + albumin-bound

Front 11

MA of androgens

Back 11

Pass through cell membrane
Bind to cytosolic receptors
Activate specific genes

Front 12

Testosterone action

Back 12

Acts at androgen receptors
Coverted to DHT in peripheral tissues
Converted to estrogen in specific tissues (e.g. brain)

Front 13

Androgen production in males? Females?

Back 13

95% testes, 5% adrenals

1/20 of males, equal synthesis in ovaries and adrenals

Front 14

5 actions of androgens

Back 14

1. Growth and development
2. Development of male sex organs
3. Male sex drive and performance
4. Development of secondary sex characteristics
5. Spermatogenesis

Front 15

How do androgens act to develop male sex organs?

Back 15

UG tract virilization by 2nd trimester testosterone increases

Front 16

Testosterone and secondary sex characteristics

Back 16

Seminiferous tubules, epididymus, vas deferens, muscle, larynx

Front 17

DHT and secondary sex characteristics

Back 17

External characteristics
Growth of penis, scrotum, pubic hair, sebaceous glands, and beard (later baldness)

Front 18

DHEA (converted to estrogen and testosterone) and secondary sex characteristics

Back 18

Growth in adolescent females, important during fetal periods

Front 19

Oral anabolics

Back 19

modified at 17 alpha position
can cause liver damage

Front 20

Injectable androgens

Back 20

Modified at 17 beta (prolongs absorption)

Front 21

Side effects of abusing adrogens

Back 21

Decreased libido
Impotence
Testicular atrophy
Gynecomastia
Toxicity

Front 22

Congenital Adrenal Hyperplasia

Back 22

21 hydroxylase def.

Increase ACTH, urinary metabolism of progesterone and plasma DHEA

Precocious puberty in males, masculinization in post puberty females

Front 23

Pseudohermaphroditism and treatment

Back 23

Lack 5 alpha reductase

T not converted to DHT
Phenotype more female than male

Treat with plastic surgery and estrogen

Front 24

Testicular feminization

Back 24

external female phenotype

Adrogen binding site or DNA binding site mutations

Aromatase in mammary tissues produces estrogen

Leads to breast development in men

Front 25

Hypogonadism treatment

Back 25

Injectable androgens need
Lg. doses need to induce spermatogenesis

Front 26

Andropause

Back 26

Concentration of testosterone decreases 1-2%/yr after age 30

By 70 production reduced at least 50%

Front 27

What can therapy do for those w/andropause

Back 27

Increased muscle strength
Increased libido
Increased sense of well being

Front 28

What are the treatments for Andropause

Back 28

Testoderm patch- taped to scrotum
Androderm patch
Androgel- rubbed on shoulders

Front 29

Treatment for endometriosis or fibrocystic dz of the breast?

Back 29

Danazol or Stanozol for 1-2 months

Front 30

SE of Danazol or Stanozol

Back 30

Facial and body hair

Deepening of voice-irreversible

Clitoral enlargement-reversible

Front 31

Hereditary Angioedema and treatment

Back 31

Impaired C1-esterase inhibitor--overactive complement--increased blood vessel permeablity

Orally active adrogen (e.g. danazol)

Front 32

How much of an androgen is needed to treat anemia?

Back 32

Large doses

Front 33

Adverse effects of androgen therapy

Back 33

Percocious puberty
Premature closure of epiphyseal plates
Virilization in women
Jaundice

Front 34

name 4 Androgen Receptor Antagonists (ARAs)

Back 34

1. Cyproterone acetate
2. Flutamine
3. Finasteride
4. Dutasteride

Front 35

Cyproterone acetate

Back 35

Used for hirsutism in women

Front 36

Flutamine

Back 36

Used in metastatic prostate cancer

Front 37

Finasteride MA and use

Back 37

Blocks prostate 5 alpha reductase (no T---DHT)
BPH and baldness

Front 38

Dutasteride

Back 38

Blocks 1 and 2 5 alpha reductase, effective in all tissues

Front 39

Natural estrogens

Back 39

Estradiol* main product of ovary

Estriol
Estrone
Premarin (from pregnant mare)

Front 40

What does estrogen do in the embryo

Back 40

Formation of vagina
Formation of uterus and tubes

Front 41

Affects of estrogen

Back 41

2nd sex characteristics
Stabilizes blood cells in skin
Bone strength
Promotes growth of uterus

Front 42

At puberty estrogen stimulates

Back 42

Axillary pubic hair
Distribution of body fat
Ductal and stroma development of breasts
Endometrial development
Growth of long bone and eventual closure

Front 43

Where are estriol and estrone produced?

Back 43

Liver

Front 44

Where can estrone be produced?

Back 44

Male and female adipose tissue

Front 45

Estrogen modified in the 17 alpha position does what?
Name two drugs like this

Back 45

1)Becomes orally active
2)Ethinyl estradiol and Mestanol

Front 46

Equine estrogens are usually conjugated w/what?
Name two drugs like this

Back 46

SO4- avoids first pass metab.
e.g. Equilenin and equilin(Premarin)

Front 47

When do you begin treatment for hypogonadism in women?

Back 47

11-13 years

Front 48

Menopausal symptoms and sequelae

Back 48

Hot flashes
Memory problems
Osteoporosis

Front 49

What risk does HRT increase?

Back 49

MI (Increased HTN, decreased HDL)

Front 50

Why was the estrogen-progesterone study halted?

Back 50

Increased risk of MI, stroke, blood clots, and breast cancer

Front 51

Why was the estrogen replacement study halted?

Back 51

Increased risk of stroke and MI

Front 52

Name 3 SERMS
(selective estrogen receptor modulators)

Back 52

Tamoxifen
Raloxifene
Clomiphene

Front 53

Tamoxifen use? Risks?

Back 53

Osteoporosis protection, adjuctive treatment to prevent reurrent breast cancer

Thrombosis

Front 54

Raloxifene location of action

Back 54

Antagonist at breast and endometrium

Agonist at bone

Front 55

Raloxifene fxn and use

Back 55

Protects agains osteoporosis
Decreased postmenopausal bone reabsorption
Decreased incidence of breast cancer

Front 56

Clomiphene SE and use

Back 56

Enlargment of ovaries
Induction of ovulation
*partial estrogen agonist