Female Sex Hormones Flashcards
What are sources of estradiol?
Menstrual cycle
Pregnancy
Menopause
Follicular phase: theca/granulosa cells
Luteal phase: CL
Pregnancy: fetoplacental
Menopause: Adrenal/hepatic conversion of precursors
Describe the physiological role of estrogen for maturation and endometrium
Female maturation: primary and secondary sex characteristics, closure of epiphyses of long bones, areolar and genital skin pigmentation
Endometrial effects: proliferation of endometrial lining (follicular phase), hyperplasia
Describe the physiological role of estrogen in cardiovascular/hematological systems, metabolism and bone
CV: enhanced coagulability, increased HDL
Metabolic: increases leptin production
Bone: Promotes apoptosis of osteoclasts (less bone resorption)
What are the physiological roles of progesterone?
Androgen precursor
Promotes proliferation of endometrium and prepares it for implantation
Renders uterus refractory to oxytocin until labor
Describe the four types of steroid receptor ligands.
Agonist: binds receptor, complex binds HRE in nucleus and recuits co-activator to ∆gene tx
Antagonist Type I: No binding of HRE
Type II: Recruitment of co-repressor
Type III/IV: Mixed agonist/antagonist
What are four ways we manipulate pathway for estrogens? Provide an example for each.
Receptor agonists: HRT
Receptor antagonists: Mifepristone (antiprogesterone)
Receptor modulators: SERM
Synthesis inhibitors: Aromatase inhibitors
Name the exogenous estrogens: Both steroidal and non steroidal.
Steroidal: Ethinyl estradiol and mestranol
Nonsteroidal (Di/Meth): Methestrol, diethylstilbestrol, dinestrol
What are the indications for giving estrogen as a therapy? (3)
Primary hypogonadism or secondary estrogen deficiency
Suppression of ovulation (contraception)
Post-menopausal estrogen replacement
What were the risks/benefits of using estrogen for osteoporosis?
Relieves hot flashes/night sweats, relieves vaginal atrophy/dryness, reduces bone loss and hip fractures, reduces risk of colon cancer
Increased thrombosis, stroke endometrial, ovarian and breast cancer, and MI
What are SERMs? How do they work?
Selective Estrogen Receptor Modulators: they are agonists/antagonists depending on the tissue
They are type III/IV receptor ligands that can either recruit co-repressor or activator to alter gene transcription
Describe Tamoxifen: MOA and clinical uses. Is it tumoricidal or tumoristatic?
A type IV antagonist that suppresses E2 dependent growth of breast cancer. Agonist in uterus bone and maybe CVS
It is tumoristatic
What is raloxifene? MOA and clinical uses
Raloxifene a type III antagonist that suppresses E2 dependent growth of breast and uterine tissue. It’s an agonist in bone and CVS that can also be used for osteoporosis.
It is tumoristatic
What is MOA of estrogen synthesis inhibitors? Name two examples and provide their indication.
Anastrozole and exemestane are aromatase inhibitors that are used in the treatment of ER+ tumors
What are the indications for progestin therapy? (4)
Replacement therapy
Contraception/IVF
Endometriosis
Dysfunctional uterine bleeding
What is the method of action of mifepristone (RU486)?
It’s a type II antagonist. It binds Progesterone receptor and HRE but recruits co-repressor to turn off gene transcription.
