Female Sex Hormones Flashcards
What are the three naturally occurring steroidal estrogens?
Estrone, estrodiol, estriol
Where and how is estradiol (E2) produced?
Follicular phase: theca and granulosa cell of graafian follicle After ovulation: corpus luteum During pregnancy: fetoplacental unit During menopause: adrenal and hepatic conversion of precursors
Where are estrone and estriol formed and from what?
Liver from estradiol or in peripheral tissues from androstenedione
What converts androgens to estrogens?
Aromatase
What is the physiological role of estrogen during female maturation?
-Dev of vagina, uterus, fallopian tubes -2ndary sex characteristics -Closure of epiphyses of long bones -Areolar and genital skin pigmentation -Fat redistribution
What are the endometrial effects of estrogen?
-Proliferation of endometrial lining in follicular phase -Endometrial hyperplasia
What are the cardiovascular-hematologic effects of estrogen?
-Enhances coagulability of blood -Increase HDL and TGs -Contributes to normal vascular structure and function -vasodilation?/??
What are the metabolic effects of estrogen?
-Increase production of leptin -Increased biosynthesis of binding globulins like TBG, fibrinogen, transferrin etc
What are the bone effects of estrogen?
Promotes apoptosis of osteoclasts, dec resorption of bone
Where and how is progesterone produced?
-Non pregnant: corpus luteum -Pregnant: placenta
What is progesterone a precursor to?
Estrogens, androgens, corticosteroid hormones
What does progesterone do to the endometrium?
Promotes proliferation and prepares it for implantation
What does progesterone do to uterus?
Renders it refractory (reduces response) to oxytocin until onset of labor
List the 4 types of steroid receptor ligands
- Pure agonist (full agonist, amplified gene transcrip) 2. Mixed agonist/antagonist (Type 3/4 antagonist, tissue specific recruits co-repressor or activator, altered gene transc) 3. Pure antagonist (Type II antagonist, requires co-repressor, no gene transcription) 4. Pure antagonist (Type I, no gene transcription)
Why use estrogen agonists?
-Treats primary hypogonadism -Secondary estrogen deficiency -Suppresses ovulation -Post-menopausal estrogen replacement (HRT)
What are the benefits to HRT?
-Relieves hot flashes and night sweats -Relieves vaginal dryness and atrophy -Reduces bone loss and hip fractures -Reduces risk of colon cancer (EPT)
What are the risks to HRT?
-Increases risk of thrombosis -Inc risk of stroke -Inc incidence ovarian and endometrial cancer (ET) -Inc in breast cancer (EPT) -Inc risk of MI (EPT)
Why use estrogen receptor modulators?
We want an antagonist at female reproductive tissues and an agonist for bone
What is SERM?
Selective estrogen receptor modulators (SERM) -Type III-IV Antagonist -Requires tissue-specific co-activator or co-repressor be recruited to work and alter gene transcription
Why do we use SERM?
Treatment of ER+ breast cancers
Name two SERMs
Tamoxifen and Raloxifene
Who do we give tamoxifen to?
Post-menopausal women or women without a uterus because it is an agonist for uterus, bone and maybe CVS
What is temoxifen?
Type IV estrogen receptor modulator -Suppresses E2 dependent growth of breast cancer (antagonist) -Tumoristatic and not tumoricidal
Who do we give raloxifene to?
Safe for women of any age/menopausal status
What is raloxifene and how does it work?
-Type III estrogen receptor modulator -Suppresses E2 dep growth of breast AND uterine tissue -Agonist in bone and CVS -Changes bone density for the better -Lowers LDL cholesterol -Tumeristatic and not tumoricidal (ie not chemotherapeutic)
How do estrogen synthesis inhibitors work? What do we use them for?
Inhibit aromatase enzyme (inhibit final step in estrogen biosynth) -Treat ER+ tumors
What do we use progestin therapy for?
-Replacement therapy -Contraceptives and IVF -Endometriosis -Dysfunctional uterine bleeding
What is RU486?
Progesterone type II antagonist (ie req co-repressor)
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