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Gonadal hormones Flashcards

1
Q

Average age of menarche

A

12.43 years

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2
Q

Average age of menopause

A

45 years

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3
Q

How long do mentrual cycles last overall?

A

32 years

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4
Q

GnRH name

A

gonadotropin releasing hormone

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5
Q

GNRH number of amino acids?

A

decapeptide

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6
Q

Receptor of GNRH, what is stimulated, cascade

A

GPCR - Gq/11-PLC/DAG+IP3

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7
Q

Function of GnRH

A

Stimulates release of
LH- lutenizing hormone
FSH - follicle stimulating hormone
both from anterior pituitary

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8
Q

Inhibin

A

Inhibin A alpha+ betaa or Inhibin B alpha+ beta-b
produced by granulosa cells
function: inhibit FSH release - inhibit double ovulation

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9
Q

How is GnRH released?

A

In a pulsatile manner, if want ovulation: higher pulsatile frequency

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10
Q

Theca cells function pathway

A

Has LH receptors
LH binds
cAMP
PKA
Converts cholesterol –> androstenedione

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11
Q

Subsequent granulosa cell pathway

A

Has FSH receptors
FSH stimulates FSHr –> cAMP –> PKA
activates aromatase
Aromatase converts androstenedione –> estrone
17HSD 1 converts to estradiol
17HSD 2 converts estradiol back into estrone

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12
Q

AMH

A

anti-muellerian hormone

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13
Q

GNRH signalling

A

Binds to GNRH receptor– GPCR
PLC pathway
PIP2 –> DAG + IP3
DAG –> PKC direct LH FSH gene expression + secretion
PKC –> Raf –> MEK –> ERK –> PLA2–> LH FSH gene expression and secretion
IP3 –> ER –> Increased Ca++–> will activate PKC and downstream effects

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14
Q

Where are GnRH receptors?

A

in pituitary bc GnRH released from hypothalamus

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15
Q

LH FSH hCG what is similar
amino acids
other similar

A

alpha subunit
92 aa
TSH

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16
Q

LH FSH hCG what is different amino acid #

A

beta subunit unique
FSH - 111aa
LH - 120aa
hCG- 144aa

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17
Q

half lives hours
LH
FSH
hCG

A

FSH 3-4
LH 20
hCG 24

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18
Q

where is hCG from

A

placenta

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19
Q

function and receptors of FSH

A

stimulate growth and recruitment of immature follicles
receptors GPCRs Gs (Gq, Gi)

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20
Q

promiscuous receptors prinicple

A

if low concentration, will bind to main receptor
if high, will bind to various G proteins

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21
Q

LH functions

A

Triggers ovulation
maintains corpus luteus

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22
Q

LH receptors and what they bind

A

Receptor - GPCR Gs (Gq)
binds LH and hCG
Ana301 says that you can stimulate ovulation with hCG as well

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23
Q

Pharma types of gonadotropins

A

Long-acting GnRH agonists
GnRH agonists
GnRH antagonist
Synthetic progestins

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24
Q

Long-acting GnRH agonist

A

Lutrepulse, Zoladex
against amenorrhea – inducing ovulation

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25
GnRH agonist
Lupron inhibit estrogen production - shrink fibroids
26
GnRH antagonists
For fertility treatment Ganirelix Cetrolerix Prevent premature ovulation
27
Synthetic progestins
For fertility treatment DHEA Fertinorm hCG - pregnyl increase testosterone production--> aromatase --> estrone...
28
Classical ER signalling
receptor in cell bind estrogen hetero homodimerization in nucleus estrogen response element altered transcription
29
Estrogen effects
Growth Reproduction Bone Cardio-vascular (heart and vessels) Gonadotropin regulation
30
is classical ER pathway only?
no estrogen activates GPCR and other kinase pathways
31
ER alpha vs beta
ER alpha: breast, ovary, endometrium, bone ER beta: bone, endothelium, brain, heart
32
Progesterone functions
Uterine development Gonadotropin negative feedback Suppresses ovulation Thermogenesis
33
Where are progesterone receptors expressed? Not cv system, that’s estrogens job
Brain, uterus, ovary, mammaries
34
Pharma uses of estrogens and progestins
Female maturation, primary hypogonadism Fertility control: Oral contraceptives Menopause: Hormone replacement Menstrual disorders: amenorrhea- no menses; dysmenorrhea - irregular menses; dysfunctional menstrual bleeding Endometriosis
35
Goal of oral contraceptives
Prevent ovulation inhibit LH surge inhibit development of endometrium
36
Contraceptive =
Estrogen + progestins
37
Mechanism of estrogen in contracep
Sensitize hypothalamus and pituitary to progestin Maintains sex characteristics
38
Mechanism of progestin in contracep
Negative feedback FSH LH Inhibit ovulation Prevent implantation Thickening of cervical mucus prevent motility of sperm
39
Course of oral contraceptives
Estrogen + Presestin 21 days on + 7 days off menses are 3 days after being off
40
Three formulations of oral contraceptives
Monophasic - all 21 pills - same amt of estrogen+ progesterone Biphasic - 2 different amounts of estrogen(ethinyl estradiol) and progestin - norethindrone Triphasic- 3 different amt estrogen and progestin - d-norgestrel
41
the estrogen used in formulation
ethinyl estradiol
42
progestins in biphasic and triphasic
biphasic - norethindrone triphasic - d-norgestrel
43
Advantage of multi-formulation
Resemble physiology optimal suppression of gonadotropins best endometrial support limited steroid exposure
44
Benefits of birth control
>98 effective birth control against: menstrual disorders iron deficiency, anemia benign breast disease ovarian cysts or cancer chance of endometrial carcinoma osteoporosis colon cancer
45
Adverse effects of birth control
Lower: glucose tolerance lipid metabolism Higher: Stroke risk DVT - thrombosis on flight Nausea edema Headache, migrane Hypertension Liver disease risk
46
Therapeutic amenorrhea
365 day contraception menstrual supression Lybrel, Seasonale
47
Mode of administration Lybrel Seasonale
Oral combined, sometimes only progestin / daily Combined transdermal/weekly Vaginal rings - monthly SQ depot medroxy progesterone acetate / 12 weeks
48
Side effects Lybrel/seasonale
Spontaneous breakthrough bleeding in early use
49
Another side effect in lybrel or seasonale
Thromboembolic disease 3 fold increased risk due to estrogen concentration Should not take after 35 years age smoking increases risk
50
Emergency contraception and chemical abortion
Plan B - Levonorgestrel Ulipristal - Ella RU - 486 Mifepristone
51
Levonorgestrel
Plan B OTC in Canada Within 72 hr 80% effective Inhibits ovulation, fertilization
52
Ulipristal
Ella Progesterone antagonist/partial agonist Delays ovulation Antagonist at endometrium emergencies within 5 days
53
RU 486
Mifepristone Within month-2 Terminate pregnancy Progesterone antagonist Mioprostol (prostaglandin) administered 48 hr later
54
What happens in menopause and what are risks?
Estrogen levels decrease High FSH LH circulation some peripheral conversion of adrenal androgens Medical risks: Bone loss CVD Alzheimer's
55
When and for what was HRT used for women
Used for over 20 years to prevent heart disease and osteoporosis in post-menopausal women
56
why was HRT for menopausal women discontinued?
Study with Premarin with and without Provera (progestin) Heart disease Breast cancer Clots strokes but: lower colon cancer lower hip fractures
57
Safer HRT administration
Use <5 years after menopause Lower premarin dose safer
58
What happens when safer administration
Decreased menopausal symptoms 90% Decreased mortality No increase in heart disease No increase in breast cancer
59
Typical menopause symptoms
Hot flashes Vaginal atrophy Bladder overactive
60
HRT Contraindications absolute
Thromboembolytic disease CVD Estrogen-dependent cancer Liver disorder Uterine bleeding Pregnancy Migrane
61
HRT contraindications relative
Hypertension Gestational diabetes Elective surgery
62
3 estrogen drugs As hrt
17 beta estradiol Premarin 17-alpha alkyl estrogen
63
17 beta estradiol Administration
patch tablets creams
64
Premarin
from mare urine Tablets creams
65
17 alpha-alkyl estrogen
Tablets oral contraceptives
66
3 Progestins
Medroxyprogesterone acetate - Provera also used in seasonale 17-alpha-alkyl-19 nor testosterones Drospirenone
67
Medroxyprogesterone acetate - Provera administration when to use
3 oxo delta 4 progesterone derivative Injectable depot Endometriosis HRT
68
17 alpha alkyl testosterones
Norethindrone Norgestrel Desogestrel oral contraceptives
69
Drospirenone
Yazmin - Yaz - oral contraceptives Anti-mineralocorticoid activity thromboembolism risk increase
70
Which drugs decrease efficacy of steroids
Anticonvulsants Antibiotics Sedatives
71
Steroids affect efficacy of which drugs?
Antidiabetic drugs - decreased glucose tolerance Caffeine/theophylline/corticosteroids/ beta blockers
72
Antiestrogens
Stilbenes Tamoxifen
73
Stilbenes
Trans conformation Estrogen antagonist ERalpha
74
Tamoxifen
mixed agonist antagonist Antagonist in breast cancer Retains uterine, bone and serum lipids
75
Tamoxifen and metabolism
endoxifen 100x more potent produced via CYP3A4 and CYP2D6 and in other order
76
Contraindications for tamoxifen
CYP2D6 poor metabolizer 7-10% SSRIs inhibit CYP2D6 (Paroxetine/Paxil - hot flashes, depression)
77
What is tamoxifen replaced with
Aromatase inhibitors
78
Aromatase conversion
Testosterone --> Estradiol Andostenedione --> Estrone Estrone converts to Estradiol without Aromatase
79
Non steroidal aromatase inhibitors
Anastrazole (Arimidex) Letrozole (Femera) Competitive
80
Steroidal aromatase inhibitors
Examestane (Aromasin) Non-competitive
81
How aromatase inhibit used How long used
As adjuvant therapy 5 years max
82
Side effects of aromatase inhibitors
Hot flashes bone lipids arthralgia - joint swelling
83
Bioactive metabolites of testosterone +enzyme
Aromatase --> Estradiol - bone protection in males 5alpha reductase --> Dehydroxytestosterone
84
DHT for?
External genitalia differentiation hair growth at puberty libido
85
what is testosterone for
Wolffian duct development libido Erythropoiesis Skeletal muscle mass/strength
86
BPH
Benign prostatic hyperplasia
87
Symptoms of BPH
Urinary frequency and urgency Weak intermittent urine stream Incomplete voiding of bladder
88
BPH prevalence
20-50% of males 40-60 years old
89
Causes of BPH
uncertain DHT in prostate
90
Pharma treatment of BPH
Aza-steroids 5alpha reductase inhibitors Finasteride Dutateride
91
action and onset of BPH Of 5 alpha reductase inhibitor
Slow onset 3-6 months inhibit growth shrink gland

PCL469 (6 decks)

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