Pharm Final: Gonadotropins
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Pharm Final: Gonadotropins
What are the 4 hormones excreted from the ovary?
What are the 3 hormones excreted from the testicles?
2. Androgen binding protein
GnRH is affected by which 3 hormones NT and do they inhibit or stimulate?
1. Dopamine--> (-) inhibits
2. Endorphins--> (-) inhibits
3. NE--> (+) stimulates
Of the 2 estrogen receptors ER-a & ER-b, which is a negative feedback?
Negative feedback--> ER-a
Fast pulse of GnRH released from the hypothalamus produces FSH or LH? Slow pulses?
Fast pulses--> LH
Slow pulses--> FSH
Low levels of estrogen stimulate or inhibit FSH?
Low levels E2--> stim FSH
High levels E2--> inhibit FSH
Low levels of progesterone stim or inhibit FSH?
Low levels Pg--> STIM FSH
What are the 3 effects of FSH on the follicle?
1. Stimulate granulosa cells to release E2
2. Aromatizes androgens to E2
3. Induces LH receptors on theca cell
What is the effect of LH?
1. Stimulates ovulation (switches cells to Pg production)
What does the LH surge do?
1. Luteinizes theca & granulosa cells (produce Pg)
2. Inhibit further cell growth
3. Drives oocyte into 1st meiotic division
4. Weakens wall of follicle
What are 3 disruptions to the cycle?
2. Weight loss
3. Pituitary adenomas
What are the 3 types of estrogen and where are they excreted?
1. E2--> ovaries
2. E1--> fat
3. E3--> placenta
Where is a majority of estrogen excreted?
What are the adverse SE of synthetic E2 1st pass effect in liver?
-Increased clotting factors
-Increased plasma renin substrate
What is the MOA of synthetic estrogen?
-Disassociates from SHBG--> binds to ERa or ERb--> changes conformation--> releases HSP
-Binds to estrogen response elements--> often a promotor gene
Where is ERa mainly expressed? ERb?
ERa--> uterus, liver, kidney, and heart
ERb--> ovary, prostate, lung, GI, bladder, heme, CNS
Both--> mammary, epididymis, thyroid, adrenal, bone, some brain
What are 4 generalized effects of estrogen?
1. Female maturation
2. endometrial regulation
3. Metabolic/cardio effects
: Pg receptor synthesis, libido, SNS well-being, fluid shifts (bloating)
What are the uses of Estrogen?
1. Primary hypogonadism
2. Postmenopausal HRT
: Hemorrage (ob)
4. Ovulation suppression
What are the benefits and risk of E2 only?
: ⇓ hot flashes, osteoporosis, Br Ca
: ⇑Blood clots, stroke, CAD
What are the risk/benefits of E2 + Pg?
: ⇓ Hot flashes, osteo, colorectal cancer
: ⇑ Blood clots, stroke, CAD, Br. Ca
What is the difference in risk fo E2 only and E+P?
E+P has increase risk for Breast Cancer
What is the difference in benefit between E2 only and E + Pg?
E+P has added benefit if decreased colorectal cancer risk
What are some random other uses of Estrogen?
Growth in girls
Trauma liver injury
Where is the primary source of progesterone synthesis?
--> also in testis, adrenal gland, and placenta
How is progesterone excreted?
Renally (almost complete 1st pass in liver)
-Ligand-receptor complex--> activate gene transcription
-Depends on receptor coregulators
T or F. Progestin has little impact on protein?
True--> favors fat deposition
What are the effects of progestin on carbs?
-Increase basal insulin
-Increase insulin response to glucose
-Promote glycogen storage
T or F. Progestin competes w/ aldosterone & mineralocorticoid receptors.
True--> ⇓ NA reabsorption--> increase aldosterone secretion
T or F. Synthetic progestins don't alter respiratory function.
True--> natural do
What is the effect of progestin on the endometrium?
-maturation and secretion
What are the therapeutic uses of Pg?
1. hormone replacement
What are 3 contraindication of Pg?
1. Increase BP in women
2. Androgenic synthetic Pg--> decrease HDL
3. Postmenopause--> Increase Br Ca risk
Inhibit increases or decreases FSH secretion?
Activin increases or decreases FSH secretion?
What is the action of Activin with FSH? Activin with LH?
Activin w/ FSH--> stimulates granulosa cells to synthesize Pg & aromotase
-Activin w/ LH--> ⇓ Pg, but markedly increases aromatase
-Synthesized by luteinized granulosa cells
-Found in ovary, placenta, uterus, & blood
-Insulin-like--> increase glycogen, H20 reuptake in myometrium, decrease uterine contractility
-Clinical trials--> dysmenorrhea, premature labor
What are the 2 Progestin families?
Selective inhibition of pituitary
T or F. Progestin only may NOT inhibit ovulation.
What are the 3 physical effects of combined E+P?
1. Mimics pregnancy--> inhibits ovulation
2. Alters cervical mucous
3. Alters tubal motility
T or F. Progestin only alters tubal motility?
False (E+P does)
What is the effect of progesterone on the uterus?
Atrophic endometrium (unless E added)
What is the effect of progestin on the binding globulins in the body?
Increased! (TBG, CBG, SHBG)
What are the effect of progestin on lipids?
-Increase TG and HDL
T or F. Pg causes increased insulin resistance.
True (and decreased carb absorbed from gut)
What is the effect of progestin on the RAAS?
-Increase plasma renin--> increase aldosterone
What is the effect of Pg on the cardio system?
-Increased BP, HR (may be profound in some women)
What are "mild" adverse side effects of Pg?
-Nausea, mastalgia, BTB, edema (E effects)
-H/A, worsening migraines
What are some "moderate" effects of Pg (+E)?
-BTB only in Pg
-Wg gain (depo)
-pigmentation (cholasma, linea nigra)
-Bacturia (ureteral dilation)
Severe Adverse SE of Pg (+E).
-Thromboembolism (VTE, MI, CVA)
: jaundice, gallbladder
-Cancer (reduced ovarian/endo)
Contradindations for OCPs?
-Unexplained vag bleeding
: liver dx, asthma, eczema, migraine, DM, HTN, optic/retrobulbar neuritis, seizure d/o
What drug is a competitive partial agonist inhibitor working at the Estrogen receptor?
Which drug is a partial E2 agonist?
Which is the effect of clomid?
inhibits negative feedback--> increasing FSH (good to improve ovulation)
What are the adverse effects of clomid?
-H/A, constipation, allergic skin rxn
-Increase endometrial implant growth
-N/V, depression, fatigue, breast tenderness, wt gain
What is the MOA of Mifepristone?
Binds tightly to Pg receptor (inhibiting Pg activity)
What are the uses of Mifepristone?
-Experimental--> endometriosis, cushings, Br Ca
What are the adverse effects of Mifepristone (Pg inhibitor)?
-V/D, abdominal/pelvic pain
-Binds to androgens, progesterone & glucocorticoid receptors
What are the effects of Danazol?
-Suppress ovarian function (inhibit LH surge)
-Inhibit gonadal function
What is Danazol used for?
-Breast pain, hemophilia, Xmas Dx, ITP, angioneurotic edema
What are adverse effects of Danazol?
1. Wt gain, edema, decrease breast size, acne, increased hair growth, deepening voice, H/A, hot flashes, libido changes, muscle cramps, adrenal suppression
What is the effect of Aromatase Inhibitors? When is it used?
-Inhibits estrogen synthesis
-Uses in Breast Cancer
What weak estrogens are produced in the testis?
**majority secreted from adrenal glands
Discuss Androstenedione, DHEA, DHEAS
-Produced in adrenal gland
-Important for "well-being"
-⇑ SHBG binding w/ ⇑ E, thyroid hormone, cirrhosis
-⇓ SHBG binding w/ ⇑ androgen, GH, obesity
-33% bound to albumin
What substance converts Androgen to dihydrotestosterone?
What substance converts Androgens to Estrodiol?
Aromatase (fat, liver, hypothalamus regulation)
What are 5 effects of androgens?
1. Growth (ht, wt, lean m. mass)
2. Genital (growth, prostate, seminal vesicle)
3. Skin (puberty hair, sebaceous glands, darkening of skin
4. Larynx & vocal cords thicken
5. Sexual function
What are the uses of synthetic androgens?
1. anabolic effects
2. hormone replacement
When is androgen replacement used?
-Hypopituitarism (gradually increase dose for growth spurt & 2nd sexual characteristics
**only use GnRH if spermatogensis is goal
Adverse effects of Androgens?
: masculinization, progestational activity, endometrial bleeding, atherosclerotic dx
-Infants--> over/under masculinzation of genitalia
-Men--> acne, sleep apnea, erythrocytosis, gynecomastia, azoospermia
-Everyone--> Na+ retention/edema, hepatic dysfunction
What are cautions/contraindications of Androgen replacement?
-NOT in pregnancy
When is androgen suppression use?
-Advanced Prostate cancer
-Androgen overproduction (use steriod synthesis inhibitor like ketoconazole)
What are 3 ways to suppress androgen and a drug example of each?
1. Steroid synthesis inhibitors (ketoconazole)
2. Halt steroid conversion (Finasteride)
3. Receptor inhibitors (Flutamide & spironolactone)