12 - Sex Hormones

Question 1

What are the primary sites of production of sex hormones?

Answer 1

• Ovaries, testes
• Placenta
• Adrenal gland
• Prostate

Question 2

What are the 3 main types of sex hormones? Which are female and which are male?

Answer 2

• Estrogens (female)
• Progestagens (female)
• Androgens (male)

Question 3

What are synthetic analogs of progestagens called?

Answer 3

Progestins

Question 4

What is the function of hCG (human chorionic gonadotropin)?

Answer 4

Sustains luteal phase during pregnancy by stimulating corpus luteum to release progesterone and estradiol, which inhibit the next round of ovulation and menstruation

Question 5

When is estradiol released? What do it do?

Answer 5

• Released by mature follicle to create proliferative endometrium
• Triggers release of LH

Question 6

What is the function of luteinizing hormone?

Answer 6

Triggers ovulation and initiates formation of corpus luteum

Question 7

What is the function of progesterone?

Answer 7

• Stimulates and maintains secretory endometrium
• When levels subside, menstruation begins
• Stimulates thickening of cervical secretions to decrease sperm penetration
• Stimulates breast lactation

Question 8

Where is estradiol production the highest?

Answer 8

Ovaries

Question 9

Is estradiol production higher during menstruation or during pregnancy? Why?

Answer 9

1000x more during pregnancy to inhibit ovulation

Question 10

What effect does estradiol have on calcium?

Answer 10

Inhibits Ca loss from bones by reducing production of bone resorption stimulating protein

Question 11

Where is progesterone production the highest?

Answer 11

Ovaries

Question 12

Is progesterone production higher during menstruation or during pregnancy?

Answer 12

Pregnancy

Question 13

Where is production of testosterone the highest?

Answer 13

Testes

Question 14

What is testosterone converted into and by what?

Answer 14

Converted in 5 alpha-DHT by 5 alpha-reductase

Question 15

What is the function of testosterone?

Answer 15

• Androgenic effects = dev’t of male sex characteristics

- Anabolic effects = growth of skeletal and cardiac muscle, bone, and RBC’s

Question 16

What is testosterones effect in women?

Answer 16

• Libido
• Mood
• Muscle mass and bone density

Question 17

Where is production of 5 alpha-DHT (dihydrotestosterone) the highest?

Answer 17

Scalp (hair follicles) and prostate

Question 18

Is testosterone or 5 alpha-DHT more potent?

Answer 18

5 alpha-DHT

Question 19

What can high levels of 5 alpha-DHT lead to?

Answer 19

Prostate hypertrophy

Question 20

What is needed on CYP19 aromatase for it to be able to aromatize?

Answer 20

Methyl group on A ring

Question 21

What is produced when testosterone is aromatized?

Answer 21

Estradiol

Question 22

Are the reduction products of progesterone active or inactive?

Answer 22

Inactive

Question 23

What are progesterones primarily converted into?

Answer 23

Corticosterone and hydrocortisone

Question 24

What is required for a metabolite of testosterone to be active?

Answer 24

• Trans/trans/trans backbone configuration

- Configuration at C-17 must have OH in beta and H in alpha positions

Question 25

What are estrogenic drugs used for?

Answer 25

- Hormone replacement therapy - Birth control - Certain types of cancer therapy

Question 26

What are the 3 structural classes of estrogens?

Answer 26

- Steroidal - Phytoestrogens - Non-steroidal (diethylstilbestrol and derivatives)

Question 27

Which estrogens are useful for hormone replacement therapy?

Answer 27

Conjugated

Question 28

What do phytoestrogens contain?

Answer 28

Flavone and isoflavone rings

Question 29

What is important about diethylstilbestrol? What it is indicated for?

Answer 29

- One of the most active non-steroidal estrogens | - Indicated for use in therapy for prostate cancer b/c it can suppress testosterone production

Question 30

What are indications for anti-estrogenic drugs?

Answer 30

Treatment of breast or uterine tumours w/ estrogen receptors

Question 31

Do anti-estrogenic drugs have steroidal structures? Why?

Answer 31

No, have non-steroidal structures b/c steroidal structures are too potent for therapy

Question 32

Do SERMs have agonist or antagonist activity?

Answer 32

Both

Question 33

Which structural feature of anastrozole is required to bind to the aromatase enzyme?

Answer 33

1,2-4-triazole

Question 34

What type of enzyme is the aromatase enzyme?

Answer 34

CYP isozyme

Question 35

What is the most common use of progestins?

Answer 35

Birth control (alone or in combination w/ estrogen)

Question 36

What are the 2 frequently used progestins?

Answer 36

- Medroxyprogesterone acetate | - Norethindrone

Question 37

How do estrogen and progestin work as contraceptives?

Answer 37

- By suppressing production of GnRH, LH, and FSH through a negative feedback mechanism => suppression of ovulation - Progestins also thicken cervical mucous to reduce sperm penetration

Question 38

All androgens have both ____ and ____ properties

Answer 38

Androgenic and anabolic

Question 39

Which hormones are generally used for androgen replacement therapy?

Answer 39

Testosterone derivatives w/ enhanced metabolic stability (rather than testosterone precursors)

Question 40

What is the preferred route of administration for testosterone? Why?

Answer 40

Transdermal (patch or topical gel) b/c oral testosterone is rapidly metabolized during first pass phase

Question 41

What is important about 17 alpha-alkynyl derivatives of testosterone?

Answer 41

Usually give more progestogenic action than androgenic action

Question 42

What is important about 17 alpha-alkyl derivatives of testosterone?

Answer 42

Good for oral administration b/c have higher metabolic stability

Question 43

What is important about 17 beta-ester derivatives of testosterone?

Answer 43

Good for IM/SC/transdermal administration b/c give "slow release" effects

Question 44

Which drugs are used for endometriosis?

Answer 44

Drugs that inhibit endometrial growth, like testosterone derivative danazol

Question 45

What is the mechanism of danazol?

Answer 45

- Exact mechanism unknown - Thought to act on pituitary gland and reduce release of FSH and LH, thereby reducing production of estrogen and progesterone

Question 46

What are indications for anti-androgens?

Answer 46

- Hyperandrogenism in males and females | - Benign and cancerous prostate conditions responsive to androgens

Question 47

What are sx of hyperandrogenism?

Answer 47

- Loss of scalp hair but increased growth of body hair - Acute acne - Premature menopause

Question 48

What is finasteride? What is its indication?

Answer 48

- Selective tight-binding 5 alpha-reductase inhibit | - Used in tx of benign prostatic hyperplasia

Question 49

What do androgen precursors cause?

Answer 49

Augmented biosynthesis of both active androgens and estradiol in vivo

Question 50

How can testosterone abuse be tested?

Answer 50

- Will lead to a high ratio of testosterone glucuronide to epitestosterone glucuronide - Ratio greater than 4:1 = abuse

Question 51

What are some adverse effects of abusing anabolic steroids?

Answer 51

- Premature stunted growth through early skeletal maturation (only in growing adolescents) - Reduced sperm count/shrinking of testes - Prostate hypertrophy

Question 52

What are some methods to mask steroid detection in urine?

Answer 52

- Uricosuric agents (excretion of uric acid in urine) - Diuretics - Epitestosterone - Saline injections

Question 53

What are some drugs that structurally resemble estrogens, progestagens, and androgens?

Answer 53

- Estrogenic drugs - Anti-estrogenic drugs (non-steroidal and aromatase inhibitors) - Progestins - Androgenic drugs - Anti-androgenic drugs - Muscle building and steroids abuse

Question 54

What do dehydrogenase enzymes do to a steroid?

Answer 54

Convert OH to =O and vice versa

Question 55

What do ketoreductase enzymes do to a steroid?

Answer 55

Convert OH to =O

Question 56

What do hydroxylase enzymes do to a steroid?

Answer 56

Convert a carbon w/ 2 hydrogen groups to a carbon w/ an OH group

Question 57

What do isomerase enzymes do to a steroid?

Answer 57

Move a double bond

Question 58

What do reductase enzymes do to a steroid?

Answer 58

Remove a double bond

Question 59

What do aromatase enzymes do to a steroid?

Answer 59

Remove methyl group and add double bonds to a ring to make it aromatic

Question 60

What does a conjugation enzyme do to a steroid?

Answer 60

Changes OH to O-R