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56 Cards in this Set

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Major sites of androgen synthesis
Adrenal cortex (zona reticularis)

Gonads (Testes)
Where is the major site of production in women? men?
Adrenal gland

Testes
What is androgen production controlled by?
ACTH
What are steroids synthesized from?
cholesterol
Which androgen does the adrenal produce most.
Dehydroepiandrosterone (DHEA)
What other minor products does the adrenal make.
Androstenedione
Androstenediol
Testosterone
What controls production of testosterone?
GnRH--LH--Leydig cells--Testosterone
What androgens are produced in the testes?
Testosterone
Dihydrotestosterone (DHT)
DHEA (minor)
Androstenedione
What transports androgens?
Testosterone-estrogen binding protein (30%)

Albumin (68%)

Free (2%)
What is the active fraction?
AF = free + albumin-bound
MA of androgens
Pass through cell membrane
Bind to cytosolic receptors
Activate specific genes
Testosterone action
Acts at androgen receptors
Coverted to DHT in peripheral tissues
Converted to estrogen in specific tissues (e.g. brain)
Androgen production in males? Females?
95% testes, 5% adrenals

1/20 of males, equal synthesis in ovaries and adrenals
5 actions of androgens
1. Growth and development
2. Development of male sex organs
3. Male sex drive and performance
4. Development of secondary sex characteristics
5. Spermatogenesis
How do androgens act to develop male sex organs?
UG tract virilization by 2nd trimester testosterone increases
Testosterone and secondary sex characteristics
Seminiferous tubules, epididymus, vas deferens, muscle, larynx
DHT and secondary sex characteristics
External characteristics
Growth of penis, scrotum, pubic hair, sebaceous glands, and beard (later baldness)
DHEA (converted to estrogen and testosterone) and secondary sex characteristics
Growth in adolescent females, important during fetal periods
Oral anabolics
modified at 17 alpha position
can cause liver damage
Injectable androgens
Modified at 17 beta (prolongs absorption)
Side effects of abusing adrogens
Decreased libido
Impotence
Testicular atrophy
Gynecomastia
Toxicity
Congenital Adrenal Hyperplasia
21 hydroxylase def.

Increase ACTH, urinary metabolism of progesterone and plasma DHEA

Precocious puberty in males, masculinization in post puberty females
Pseudohermaphroditism and treatment
Lack 5 alpha reductase

T not converted to DHT
Phenotype more female than male

Treat with plastic surgery and estrogen
Testicular feminization
external female phenotype

Adrogen binding site or DNA binding site mutations

Aromatase in mammary tissues produces estrogen

Leads to breast development in men
Hypogonadism treatment
Injectable androgens need
Lg. doses need to induce spermatogenesis
Andropause
Concentration of testosterone decreases 1-2%/yr after age 30

By 70 production reduced at least 50%
What can therapy do for those w/andropause
Increased muscle strength
Increased libido
Increased sense of well being
What are the treatments for Andropause
Testoderm patch- taped to scrotum
Androderm patch
Androgel- rubbed on shoulders
Treatment for endometriosis or fibrocystic dz of the breast?
Danazol or Stanozol for 1-2 months
SE of Danazol or Stanozol
Facial and body hair

Deepening of voice-irreversible

Clitoral enlargement-reversible
Hereditary Angioedema and treatment
Impaired C1-esterase inhibitor--overactive complement--increased blood vessel permeablity

Orally active adrogen (e.g. danazol)
How much of an androgen is needed to treat anemia?
Large doses
Adverse effects of androgen therapy
Percocious puberty
Premature closure of epiphyseal plates
Virilization in women
Jaundice
name 4 Androgen Receptor Antagonists (ARAs)
1. Cyproterone acetate
2. Flutamine
3. Finasteride
4. Dutasteride
Cyproterone acetate
Used for hirsutism in women
Flutamine
Used in metastatic prostate cancer
Finasteride MA and use
Blocks prostate 5 alpha reductase (no T---DHT)
BPH and baldness
Dutasteride
Blocks 1 and 2 5 alpha reductase, effective in all tissues
Natural estrogens
Estradiol* main product of ovary

Estriol
Estrone
Premarin (from pregnant mare)
What does estrogen do in the embryo
Formation of vagina
Formation of uterus and tubes
Affects of estrogen
2nd sex characteristics
Stabilizes blood cells in skin
Bone strength
Promotes growth of uterus
At puberty estrogen stimulates
Axillary pubic hair
Distribution of body fat
Ductal and stroma development of breasts
Endometrial development
Growth of long bone and eventual closure
Where are estriol and estrone produced?
Liver
Where can estrone be produced?
Male and female adipose tissue
Estrogen modified in the 17 alpha position does what?
Name two drugs like this
1)Becomes orally active
2)Ethinyl estradiol and Mestanol
Equine estrogens are usually conjugated w/what?
Name two drugs like this
SO4- avoids first pass metab.
e.g. Equilenin and equilin(Premarin)
When do you begin treatment for hypogonadism in women?
11-13 years
Menopausal symptoms and sequelae
Hot flashes
Memory problems
Osteoporosis
What risk does HRT increase?
MI (Increased HTN, decreased HDL)
Why was the estrogen-progesterone study halted?
Increased risk of MI, stroke, blood clots, and breast cancer
Why was the estrogen replacement study halted?
Increased risk of stroke and MI
Name 3 SERMS
(selective estrogen receptor modulators)
Tamoxifen
Raloxifene
Clomiphene
Tamoxifen use? Risks?
Osteoporosis protection, adjuctive treatment to prevent reurrent breast cancer

Thrombosis
Raloxifene location of action
Antagonist at breast and endometrium

Agonist at bone
Raloxifene fxn and use
Protects agains osteoporosis
Decreased postmenopausal bone reabsorption
Decreased incidence of breast cancer
Clomiphene SE and use
Enlargment of ovaries
Induction of ovulation
*partial estrogen agonist