Female hormones Pharmacology Flashcards
(46 cards)
What is the precursor for all steroid hormones
Cholesterol
What are the 3 types of estrogen. What is the main source of estrogen pre-menopause and post-menopause? where?
- Estradiol (pre-menopause, ovary)
- Estrone (post-menopause, adipose)
- Estriol
Where is Progesterone made
- Ovaries
- testes
- Adrenal
- Placenta
- Cholesterol
- Corpus luteum (ovary in the 2nd half of menstrual cycle)
Which part of the hormonal cycle does progesterone and estrogen get released?
LH and FSH relaese produces estrogen and progesterone
Where is Estrogen receptor Alpha ER-a found?
- Female reproductive tract
- Mammary gland
- Hypothalamus
- Endothelial cells
- Vascular smooth muscle
Where is ER-B found
Ovaries
(and in lower levels in lung, brain, bones, vasculature)
How do estrogen receptors work?
- Estrogen receptor agonist (ex. estradiol) enters cell –> Binds ER
- ER dissociates from heat shock proteins –> forms
- homodimer: ER-a/ER-a or heterodimer ER-a/ER-B - ER dimers binds to estrogen response
- Recruitment of co-activators –> gene transcription
Can estrogens bind GPCRs? what is its effect?
Yes
- Cause faster, non-genomic estrogenic activity
Differentiate between PR-A and PR-B
Both have identical ligand binding
PR- A
- inhibits actions of PR-B (recruiting co-REPRESSORS)
- missing first 165 N-terminal amino acids of PR-B
PR-B
- Stimulates progesterone activity (by recruitment of co-ACTIVATORS)
How do progesterone receptors work?
- PRs are found in nucleus, in an inactive state, bound to heat shock proteins
- Progesterone receptor agonist enter nucleus –> binds to PR
- Binding causes dissociation of heat shock proteins
- Receptor dimers form –> bind to progesterone response elements on target genes
(makes homodimers or heterodimers)
What are the physiological effects of estrogen (5)
- Causes endometrial proliferation
- Increases water in cervical mucous (easier for sperm to get in)
- Inc differentiation of osteoblasts, Reduces osteoclast activity (= good bones)
- Changes in lipid levels
- Changes in blood clotting factor levels
What are the physiological effects of progesterone (4)
- Inhibits endometrial proliferation caused by estrogen (matures endometrial cells instead )
- Makes cervical mucous thicker (opposite of estrogen)
- Maintains pregnancy
- Decline in progesterone at the end of cycle causes menstruation
Explain what the other ovarian hormones do:
Androgens
Inhibin
Activin
Relaxin
Androgens
- small amounts of testosterone are produced
Inhibin
- inhibits FSH production
Activin:
- promotes FSH release
Relaxin:
- Released in response to LH
What is the MOA of progesterone receptor antagonists. Give examples.
Bind and block progesterone receptors
Mifepristone (terminate pregnancy)
Ulipristal (partial antagonist)
What is the MOA of estrogen receptor antagonist. Give examples
Bind to estrogen receptors and cause dimerization + DNA binding (like estrogen)
- then recruit co-receptors –> inhibit gene transcription
Ex.
- Clomiphene
- Fulvestrant
Differentiate between Estrogen receptor antagonists vs agonists. Protein enzyme activity? relax/tighten chromatin?
Agonists (co-activators)
- Histone acetyltransferase activity
- Relax chromatin –> allow transcription
Antagonists (co-repressors)
- Histone deacetylase activity
- Tighten chromatin –> inhibit transcription
Explain how selective estrogen response modulators work (SERMs)
Alter the conformation of ER-a and/or ER-B
- unique to SERMs
- lead to different interactions with co-activators/co-repressors
- either partially estrogenic, no activity, or anti-estrogenic activity
Give examples of SERMs (2) explain them
- Tamoxifen: breast cancer
- also maintains bones - Raloxifene: Osteoporosis
- anti-estrogenic activity in breasts (reduce growing)
- estrogenic activity in bone (anti-resorptive; doesn’t break down)
Explain indirect-acting agents
Give example of an irreversible & reversible inhibitor?
Aromatase inhibitors used to block estrogen production
- used for breast cancer
- No positive effect on bone (like tamoxifen)
- Used as an add-on/second line to tamoxifen treatment
Irreversible: Exemestane (Aromasin)
Reversible: Anastrazole (Arimidex), Letrozole (Femara)
What are other compounds that have estrogenic activity
Plant-based compounds:
Soy isoflavones (used to manage menopausal symptoms)
Synthetic agents:
- Bisphenol A
What are the different types of hormonal contraceptives available?
- Estrogen/progestin combinations (COCs)
a. Fixed dose: every dose contrains the same ratio
b. Phasic: dose of each hormone varies depending on stage of cycle - Progestin-only formulations
What hormones do COCs contain?
Estrogen (ethinyl estradiol)
Progestin
ex. Desogestrel (less androgenic activity)
ex. Drospirenone (mineralocorticoid receptor antagonist)
What is the purpose of administering COCs for 21 days of 28 day cycle
Reduce exposure to hormones, but retain enough activity to maximize anti-ovulation effects
- Also to reduce breakthrough bleeding
What is the primary and secondary MOA of COCs
Primary
- The estrogen inhibits FSH secretion (inhibit follicular development)
- Progestin to inhibit LH secretion (inhibit LH surge and ovulation)
Secondary
- Progestin to alter cervical mucous (inhibit sperm passage)
- estrogen/progestin alter endometrium (decrease chance of implantation)
