12 - Sex Hormones Flashcards
What are the primary sites of production of sex hormones?
- Ovaries, testes
- Placenta
- Adrenal gland
- Prostate
What are the 3 main types of sex hormones? Which are female and which are male?
- Estrogens (female)
- Progestagens (female)
- Androgens (male)
What are synthetic analogs of progestagens called?
Progestins
What is the function of hCG (human chorionic gonadotropin)?
Sustains luteal phase during pregnancy by stimulating corpus luteum to release progesterone and estradiol, which inhibit the next round of ovulation and menstruation
When is estradiol released? What do it do?
- Released by mature follicle to create proliferative endometrium
- Triggers release of LH
What is the function of luteinizing hormone?
Triggers ovulation and initiates formation of corpus luteum
What is the function of progesterone?
- Stimulates and maintains secretory endometrium
- When levels subside, menstruation begins
- Stimulates thickening of cervical secretions to decrease sperm penetration
- Stimulates breast lactation
Where is estradiol production the highest?
Ovaries
Is estradiol production higher during menstruation or during pregnancy? Why?
1000x more during pregnancy to inhibit ovulation
What effect does estradiol have on calcium?
Inhibits Ca loss from bones by reducing production of bone resorption stimulating protein
Where is progesterone production the highest?
Ovaries
Is progesterone production higher during menstruation or during pregnancy?
Pregnancy
Where is production of testosterone the highest?
Testes
What is testosterone converted into and by what?
Converted in 5 alpha-DHT by 5 alpha-reductase
What is the function of testosterone?
- Androgenic effects = dev’t of male sex characteristics
- Anabolic effects = growth of skeletal and cardiac muscle, bone, and RBC’s
What is testosterones effect in women?
- Libido
- Mood
- Muscle mass and bone density
Where is production of 5 alpha-DHT (dihydrotestosterone) the highest?
Scalp (hair follicles) and prostate
Is testosterone or 5 alpha-DHT more potent?
5 alpha-DHT
What can high levels of 5 alpha-DHT lead to?
Prostate hypertrophy
What is needed on CYP19 aromatase for it to be able to aromatize?
Methyl group on A ring
What is produced when testosterone is aromatized?
Estradiol
Are the reduction products of progesterone active or inactive?
Inactive
What are progesterones primarily converted into?
Corticosterone and hydrocortisone
What is required for a metabolite of testosterone to be active?
- Trans/trans/trans backbone configuration
- Configuration at C-17 must have OH in beta and H in alpha positions
What are estrogenic drugs used for?
- Hormone replacement therapy
- Birth control
- Certain types of cancer therapy
What are the 3 structural classes of estrogens?
- Steroidal
- Phytoestrogens
- Non-steroidal (diethylstilbestrol and derivatives)
Which estrogens are useful for hormone replacement therapy?
Conjugated
What do phytoestrogens contain?
Flavone and isoflavone rings
What is important about diethylstilbestrol? What it is indicated for?
- One of the most active non-steroidal estrogens
- Indicated for use in therapy for prostate cancer b/c it can suppress testosterone production
What are indications for anti-estrogenic drugs?
Treatment of breast or uterine tumours w/ estrogen receptors
Do anti-estrogenic drugs have steroidal structures? Why?
No, have non-steroidal structures b/c steroidal structures are too potent for therapy
Do SERMs have agonist or antagonist activity?
Both
Which structural feature of anastrozole is required to bind to the aromatase enzyme?
1,2-4-triazole
What type of enzyme is the aromatase enzyme?
CYP isozyme
What is the most common use of progestins?
Birth control (alone or in combination w/ estrogen)
What are the 2 frequently used progestins?
- Medroxyprogesterone acetate
- Norethindrone
How do estrogen and progestin work as contraceptives?
- 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
All androgens have both ____ and ____ properties
Androgenic and anabolic
Which hormones are generally used for androgen replacement therapy?
Testosterone derivatives w/ enhanced metabolic stability (rather than testosterone precursors)
What is the preferred route of administration for testosterone? Why?
Transdermal (patch or topical gel) b/c oral testosterone is rapidly metabolized during first pass phase
What is important about 17 alpha-alkynyl derivatives of testosterone?
Usually give more progestogenic action than androgenic action
What is important about 17 alpha-alkyl derivatives of testosterone?
Good for oral administration b/c have higher metabolic stability
What is important about 17 beta-ester derivatives of testosterone?
Good for IM/SC/transdermal administration b/c give “slow release” effects
Which drugs are used for endometriosis?
Drugs that inhibit endometrial growth, like testosterone derivative danazol
What is the mechanism of danazol?
- Exact mechanism unknown
- Thought to act on pituitary gland and reduce release of FSH and LH, thereby reducing production of estrogen and progesterone
What are indications for anti-androgens?
- Hyperandrogenism in males and females
- Benign and cancerous prostate conditions responsive to androgens
What are sx of hyperandrogenism?
- Loss of scalp hair but increased growth of body hair
- Acute acne
- Premature menopause
What is finasteride? What is its indication?
- Selective tight-binding 5 alpha-reductase inhibit
- Used in tx of benign prostatic hyperplasia
What do androgen precursors cause?
Augmented biosynthesis of both active androgens and estradiol in vivo
How can testosterone abuse be tested?
- Will lead to a high ratio of testosterone glucuronide to epitestosterone glucuronide
- Ratio greater than 4:1 = abuse
What are some adverse effects of abusing anabolic steroids?
- Premature stunted growth through early skeletal maturation (only in growing adolescents)
- Reduced sperm count/shrinking of testes
- Prostate hypertrophy
What are some methods to mask steroid detection in urine?
- Uricosuric agents (excretion of uric acid in urine)
- Diuretics
- Epitestosterone
- Saline injections
What are some drugs that structurally resemble estrogens, progestagens, and androgens?
- Estrogenic drugs
- Anti-estrogenic drugs (non-steroidal and aromatase inhibitors)
- Progestins
- Androgenic drugs
- Anti-androgenic drugs
- Muscle building and steroids abuse
What do dehydrogenase enzymes do to a steroid?
Convert OH to =O and vice versa
What do ketoreductase enzymes do to a steroid?
Convert OH to =O
What do hydroxylase enzymes do to a steroid?
Convert a carbon w/ 2 hydrogen groups to a carbon w/ an OH group
What do isomerase enzymes do to a steroid?
Move a double bond
What do reductase enzymes do to a steroid?
Remove a double bond
What do aromatase enzymes do to a steroid?
Remove methyl group and add double bonds to a ring to make it aromatic
What does a conjugation enzyme do to a steroid?
Changes OH to O-R
