Estrogens - 13,14 Flashcards
Estrogens
- development and maintenance of female reproductive tissues (___, uterus, breast, ___)
- regulation in ___ (temp, mood)
- effects in ___ tissues (bone, cardiovascular, liver)
- ovaries, vagina
- CNS
- peripheral
Progesterone
- development and maintenance of female reproductive tissues (___ and ___)
- maintenance of ___
- effects in other tissues (__)
- uterus, breast
- pregnancy
- brain
17β-Estradiol
- most potent estrogen
- produced mostly in the ___
- synthesized most in the __ during pregnancy
- plasma levels ___ ng/dL
- ___ varies during the menstrual cycle
- mostly bound to ___ and ___ only ___ free in circulation
- ovaries
- placenta
- 5-85 ng/dL
- cyclically
- sex-hormone binding globulin (SHBG), albumin, 2%
Regulation of estrogen synthesis
- hypothalamus: ___
- anterior pituitary: ___ and __
- Ovaries: ___ and ___ → physiological functions and positive/negative feedback loop
- GnRH
- FSH and LH
- estrogens and progesterone
Menstrual cycle
- Granulosa cells produce ___
- Corpus luteum produces ___ and ___
- estrogen
- estrogen and progesterone
Menstrual cycle
Early follicular phase
* Estrogen suppresses the production
of ___.
FSH
prevents multiple eggs fro being released
Menstrual cycle
Late follicular phase
* estrogen stimulates surge of __ and __ → ovulation and formation of ___
- LH and FSH
- corpus luteum
Menstrual cycle
Luteal phase
* estrogen and __ suppresses the production of ___ and ___
- progesterone
- LH and FSH
Menstrual cycle
- corpus luteum ___ if pregnancy does not occur
- when production of estrogen and progesterone by the ___ declines, ___ occurs
- degenerates
- corpus luteum, menstruation
Menstrual cycle
if pregnancy occurs
* fertilized egg secretes ___, whichs acts as ___ to stimulate corpus luteum to produce ___ during the first trimester.
* higher ___ levels support maintenance of endometrium
* ___ is what is detected during a pregnancy tests.
- human chorionic gonadotropin (hCG), LH, progesterone
- progesterone
- hCG
corpus luteum doesnt degrade, sticks around to make progesterone
Biosynthesis of estrogens
- Step 1: Androstenedione can be converted to ___ by aromatase, or it can be converted to ___ by 17B-hydroxysteroid dehydrogenase.
- Step 2: estrone is then converted to 17B-estradiol by ___, or testosterone is converted to 17B-estradiol by ___
both estrone and 17B-estradiol are converted into ___, a weak estrogen
- estrone, testosterone
- 17B-hydroxysteroid dehydrogenase, aromatase
- estriol
estrone & estriol - synthesized in the liver and peripheral tissues
Types of estrogens
Natural estrogens
* 17B-estradiol - ___ potent
* estrone - ___ potent
* estriol - less potent (dominant form during ___, synthesized in the ___)
- most
- less
- pregnancy, placenta
types of estrogens
Synthetic estrogens
2 types: ___ and ___
steroidal, non-steroidal
types of estrogens
Phytoestrogens
Estrogen-mimetic compounds in ___
plants (flavonoids)
types of estrogens
Environmental estrogens
Compounds used in the manufacture of ___
plastics (bisphenols, alkylphenols, phthalate phenols)
Metabolism and excretion of estrogen
- Metabolized in the ___ mostly and excreted to the ___ and to the ___
- Conjugated estrogens in the bile can be ____ in the ____ and reabsorbed (____ circulation).
- ___ administered estrogens have a ___ ratio of hepatic to peripheral effects; can be avoided by using routes that avoid ___ liver exposure.
- liver, bile, urine
- hydrolyzed, intestine, enterohepatic
- orally, high, first pass
Physiologic effects of estrogen
Female maturation
* development of vagina, uterus, and ___
* ___ development and ___ growth in the breast
* accelerated growth phase and ___ closure
* growth of ___ and ___ hair
* body fat distribution
* ___ in the skin (nipples, areolae, and genital region)
- uterine tubes
- stromal, ductal
- epiphyseal
- axillary, pubic
- pigmentation
Physiologic effects of estrogen
Endometrial effects
* development of ___ lining during menstrual cycles
* prolonged exposure leads to ___ of the endometrium and abnormal bleeding
- endometrial
- hyperplasia
Physiological effects of estrogen
Metabolic and cardiovascular effects
* decrease in ___ resorption (estrogen deficiency can lead to ___)
* synthesis of ___ and ___
* alteration in the composition of ___ lipids (increase in ___, decrease in ___)
* blood ___
* CNS: ___
- bone, osteoporosis
- sex-homrone binding globulin (SHBG), transcortin
- plasma, HDL, LDL
- coagulation
- mood
Clinical uses of estrogens
Hormone replacement therapy in postmenopausal women
* relief of ___ disturbances: ___, sweating, flushing
* used to treat symptoms of ____: vaginal dryness, increased risk of infections
* relief of psychological effects: ___, ___, depression, nervousness
- CNS, hot flashes
- urogenital atrophy
- mood swings, insomnia
Clinical uses of estrogens
Osteoporosis
* for ___ osteoporosis only
* estrogen decrease the rate of ___ resorption
- post-menopausal
- bone
Clinical uses of estrogens
hormonal ___
contraception
Clinical uses of estrogens
Replacement therapy in patients with primary ___
* failure of ___ development
* chromosomal disorders: ___ syndrome - absence of 1 or all ___ chromosomes
* ___ (ovarian cancer)
hypogonadism
* ovary
* Turner, sex
* oophorectomy
Adverse effects
Uterine bleeding
* estrogen therapy is major cause of ___ uterine bleeding
* endometrial ___
* estrogen should be given ___
* can be prevented by the administration of a ___ in each cycle
- postmenpausal
- hyperplasia
- cyclically
- progestin
Adverse effects
Endometrial ___
* use of progestin reduces the risk
carcinoma
Adverse effects
Breast cancer
* particularly ___term use
* addition of progestin does not have a ___ effect
- long-term
- protective
Adverse effects
general adverse effects of estrogen (think PUP)
- Nausea
- headache
- fluid retention
- weight gain
Structure-activity relationship
- ___ in A ring is required
- ___at the 3 position is essential for activity
- the 3-OH can be masked as a ___ derivative which is ___ in vivo
- 16-OH ___ activity
- 17a-ethynyl ___ metabolism and allows for ___ activity
- ___ group at the 17B position required for activity. (can be temporarily blocked by an ___ for drug delivery)
- aromaticity
- hydroxyl
- ester, hydrolyzed
- decreases
- blocks, oral
- hydroxyl