Pituitary and Gonadal Hormones II Flashcards
What is inhibited until puberty?
Which neuron system is involved in this inhibition?
GnRH release
Kisspeptin, Neurokinase B and Dynorphin
Early menstrual changes are followed by what? (2)
Periodic cyclical bleeding
Secretion of GnRH, gonadotropins and ovarian hormones
Cessation of menstruation cycle :
Can still make ______
symptoms? (3)
Estrogen
Hot flashes
CV events
Osteoporosis
Steps to the menstrual cycle?
No pregnancy?
- FSH stimulates multiple follicles
- Dominant follicle grows
- LH/FSH surge, follicle rupture, ovulation and corpus hemorrhagicum formation
- Luteinized granulosa and thecal cells form corpus luteum (progesterone and estrogen)
No pregnancy : CL degenerates, endometrial sloughing and menstruation
Disturbances in ovarian function? (5)
Amenorrhea (absence of menstrual cycle)
Anovulation (absence of ovulation)
Tumors in ovary, pituitary gland and uterus
Prolactinomas (inhibition of GnRH release)
Hormonal disturbances : Tumors of adrenal gland
Three forms of estrogen?
Major form?
Estradiol (E2)
Estrone (E1)
Estriol (E3)
Major : Estradiol
Estrogen mimetic compounds? (2)
Flavonoids Plastic manufacturing (bisphenols, lkylphenols, phthalate phenols)
Biosynthesis of estrogens and testosterone? (3)
- Pregnenolone is the precursor of progesterone, dehydropiandrosterone and androstenedione
- Aromatase converts androstenedione and testosterone into estrone (E1) and estradiol (E2)
- E1 and E3 are formed in the liver from E2 and in peripheral tissues from androstenedione and androgens.
Estrogen in circulation binds to what? active or inactive?
Sex hormone-binding globulin (SHBG)
Not active
When estrogen enters the nucleus, it binds to _____ receptors.
Two receptor isoforms in the nucleus? Roles?
estrogen
ERalpha: growth promoting
ERbeta: antigrowth effects
Once estrogen binds to estrogen receptor in the nucleus, this forms _____ that bind to _______ and ________
Dimers
Estrogen response elements (ERE) and CoA/CoR (transcription and protein synthesis)
Non-genomic actions of estrogen? (2)
Binds to cell surface receptors
Activates different signal transduction pathways
Physiologic effects of estrogen:
Normal or abnormal sexual maturation?
Normal
Physiologic effects of estrogen:
Increases levels of _____ factors, decreases _______ ______ and which disease?
Clotting factors
Platelet adhesiveness
Atherosclerosis
Physiologic effects of estrogen:
liver metabolism?
increases levels of hormone binding globulins, transferrin and fibrinogen
Physiologic effects of estrogen: effects on cholesterol and TG?
Increases plasma HDL and TG
Lowers LDL and cholesterol
2 clinical uses of synthetic estrogens?
Primary hypogonadism
Hormone replacement therapy (HRT)
What is primary hypogonadism and how is it treated?
Ovarian developmental defects, surgical oophorectomy, premature menopause
Treatment : ethinyl estradiol, conjugated or esterified estrogens (equilin)
Hormone replacement therapy is used on which women?
It has beneficial effects on circulating ____ and ________
WHI found increased risks for what? (2)
postmenopausal women
Circulation lipids and lipoproteins
CV problems and breast cancer
Adverse effects and contraindications of estrogen therapies? (3)
Uterine and vaginal bleeding
Breast cancer risk
Should not be used in estrogen dependent cancer, liver disease, thromboembolic disease
What is the major progestin?
It is synthesized where? (4)
MOA similar to ___________
Progesterone
Ovary, testis, adrenal cortex, placenta
Estrogen
Progesterone :
promotes ____ and ______ deposition, increases ________ response to glucose
fat and glycogen
insulin
Progesterone :
_________ effects on the brain
hypnotic
Progesterone competes with _________ binding to _______ receptors in renal tubule and promotes renal ____ excretion
aldosterone
mineralocorticoid
Na+
Synthetic progestins have an increased half-life of how many days?
1-3
Second generation synthetic progestins are ____ compounds.
Example?
21-C
Medroxyprogesterone
Third generation synthetic progestins are ___ steroids and include ____ _________.
example?
19-nor, 13-ethyl steroids
Oral contraceptives
Norgestimate
2 clinical applications of synthetic progestins?
Hormone replacement therapy
Prolonged ovarian suppression
Hormone replacement therapy with synthetic progestins are used in which women?
Progestins are used in combination with ______
postmenopausal
estrogen
Synthetic progestins:
prolonged ovarian suppression is used for which diseases? (2)
Does it activate or inhibit gonadotropin release?
Dysmenorrhea
Endometriosis
Inhibit
Drugs/devices that prevent contraception? (4)
Spermicides
Barrier methods
Intrauterine devices
Oral, injectable transdermal
Two combinations of oral preparations of hormonal contraceptions?
1) Estrogen and progestin combinations
2) Progestins alone
2 combination preparation forms of hormonal preparations? Examples?
Monophasic form : Yasmin
Multiphasic form : Natazia
Natazia:
the amount of _______ valerate is stepped down while the amount of _______ is stepped up
estradiol
progestin
Natazia : roles? (2)
Feedback inhibition of gonadotropin release
Inhibition of ovulation
Birth control path is a combination of which two hormones?
Norelgestromin
Ethinyl estradiol
Two examples of Emergency Contraception? what do they involve?
Plan B One-Step : single dose of levonogestrel (Progestin)
Plan B Next Choice : two doses of levonogestrel
What causes a decrease in efficacy of oral contraceptives? (2)
antimicrobial agents
rifampicin
What type of drugs are Selective Estrogen Receptor Modulators (SERMs)?
Competitive partial agonist inhibitors of estradiol at ER
Where are SERMs agonists? (4)
Where are they antagonists? (2)
Liver, CV, bone and uterus
Breast and Brain
Two examples of SERMs? Role?
Tamoxifen
Clomiphene
Agonists: They act like estrogen and eliminate estrogen function
How is tamoxifen metabolized into a more potent SERM?
CYP2D6 metabolizes tamoxifen into endoxifen
2 progesterone inhibitors?
Mifepristone
Danazol
Role of mifepristone?
Binds to progesterone and glucocorticoid receptors and inhibits activities of ligands
Danazol:
Weak binding to which receptors? (3)
Inhibits what? (3)
Weak binding to progesterone, androgen and glucocorticoid receptors
Inhibits midcycle LH/FSH surge
Inhibits enzymes including P450C17
Inhibits conversion of progesterone into androstenedione and testosterone
Nafarelin is a ______ analog and inhibits what?
GnRH
Ovarian function
Anastrozole inhibits _______
aromatase
Fulvestrant is a ____ antagonist.
It inhibits the dimerization of what?
ER
Dimerization of ER and DNA binding
