Lecture 12: Estrogens Flashcards
Estrogens
-development and maintenance of female reproductive tissues
-regulation in CNS (temp, mood)
-effects in peripheral tissues (bone, cardiovascular, liver)
Progesterone
-development/maintenance of female tissues
-maintenance of pregnanct
-effects in other tissues (brain)
17B-estradiol
-most potent estrogen
-produced mostyl in ovaries of premenopausal women
-synthesized most in placenta during pregnancy
17B-estradiol plasma levels
-varies with menstrual cycle
-5-85 ng/dL
17B-estradiol states
-most bound to SHBG
-free (2%)
Granulosa cells
-produce estrogen
corpus luteum
-produces estrogen and progesterone
Menstrual Cycle
- early follicular phase
- late follicular phase
- luteal phase
early follicular phase
-estrogen suppresses FSH
late follicular phase
-estrogen stimulates LH and FSH surge
=ovulation
=forms corpus luteum
luteal phase
-estrogen and progesterone suppress LH and FSH
If pregnancy does not occur,
-corpus luteum degenerates
-estrogen and progesterone production by corpus luteum declines
=menstruation
if pregnancy occurs,
-embryo secretes hCG
-hCG acts like LH
=stimulates corpus to produce progesterone during first trimester
high progesterone levels support
maintenance of endometrium
pregnancy tests
-chromatographic immunoassays of hCG in urine
Estrone and Estiol synthesis
-synthesized in liver and peripheral tissues
-from androstenedione
-aromatase
17B-estradiol synthesis
-in ovaries
-from testosterone
-aromatase
types of estrogens
-natural
-synthetic
-phyto
-environmental
natural estrogens
-17B-estradiol (most potent)
-estrone
-estriol (least potent)
Synthetic estrogens
-drugs with estrogenic activities
-steroidal or nonsteroidal
phytoestrogens
-estrogen-mimetic compounds in plants
-“flavonoids”
environmental estrogens
-compounds used to make plastic
-bisphenols, alkylphenols, phthalate phenols
Metabolism of estrogen
-in liver
-hydroxylation in A ring
Excretion of estrogen
-to bile then to urine
-conjugated estrogens in bile can be hydrolyzed and reabsorbed
oral estrogens
-high ratio of hepatic to peripheral effects
physiological effects of estrogen
-female maturation
-endometrial
-metabolic and cardiovascular
-enhance blood coagulation
-CNS (mood)
Role of estrogen in female maturation
-development of vagina, uterus, uterine tubes
-breast growth
-accelerated growth phase and epiphyseal closure
-grow hair
-alter body fat distribution
-pigment skin (nipples, genitals)
endometrial effects of estrogen
-develop endometrial lining
-prolonged exposure = hyperplasia and abnormal bleeding
Metabolic effect of estrogen
-decrease bone reabsorption rate
-synthesize transcortin and SHBG
-increase HDL
-decrease LDL
osteoporosis cause
estrogen deficiency
Clinical uses of estrogens
-hormone replacement therapy (postmenapause)
-osteoporosis
-contraception
-replacement therapy in hypogonadism
Hormone replacement therapy in postmenapausal women
-relieve CNS effects (hot flashes)
-relieve urogenital atrophy symptoms (dry cooch)
-relieve mood, insomnia, depression, nervousness
osteoporosis
-post-menapausal only
-estrogens decrease rate of bone reabsorption
Replacement therapy in patients with primary hypogonadism
-no ovaries
-chromosomal disorders (turner syndrome)
-castration (oophorectomy)
turner syndrome
absence of one or all sex chroosomes
Adverse effects of estrogens
-uterine bleeding
-endometrial carcinoma
-breast cancer
-nausea, headache, retention, weight gain
Uterine bleeding due to estrogen
-endometrial hyperplasia
-estrogen should be given cyclically
-prevent by admin of progestin each cycle
Progestin effect on estrogen adverse effects
-prevent uterine bleeding
-reduce risk of endometrial carcinoma
-not effective for breast cancer
