endoexam2

Question 1

what kind of hormone is insulin?

where is it produced?
steps in production?

Answer 1

peptide hormone
in beta cells of pancreas
pre?pro?insulin?? converted to pro?insulin in the ER (3 chains)
pro insulin exits the ER, transits through the golgi, enters secretory

C peptide is cleaved in the secretory vesicles and mature insulin is stored in insulin granules

insulin has 2 chains

Question 2

what stimulates insulin release from beta cell? (4)

Answer 2

rise in blood glucose is primary stimulus
amino acids arginine and leucine
parasympathetic release of Ach
GI derived peptides known as incretins (GLP and GIP)

Question 3

steps involved in insulin release

Answer 3

glucose stimulates GLUT?2, which comes enters beta cell
stimulates ATP to close K channel
(also sulphonylurea can close K channel)
plasma membrane depolarizes
calcium channel opens, influx of calcium stimulates insulin secretion

Question 4

what kind of receptor is insulin receptor?
what pathways are activated?
where does insulin mainly act?
what is insulin’s action?

Answer 4

tyrosine kinase receptor that activates RAS and p13K pathway in target cell
insulin mainly acts on liver, muscle, and adipose tissue
net effect is to reduce circulating blood glucose levels

Question 5

describe insulin receptor

Answer 5

2 alpha and 2 beta subunits that are linked by disulfide bonds
alpha are extracellular, contain insulin binding domains
beta chains penetrate plasma membrane
binding of insulin to alpha subunits causes beta subunits to autophsophorylate

Question 6

insulin action in liver

Answer 6

MAPK causes cell growth and glucose utilization
liver:
glucose production decreases (inhibits gluconeogenesis, glycogenolysis)
increase fuel storage:
glucose phospohorylation, glycolysis, fatty acid synthesis, glycogen synthesis

Question 7

insulin action in muscle

Answer 7

muscle:

1. decreased glucose production (insulin action inhibits: glycognolysis)
2. increased glucose uptake (insulin action stimulates GLUT4 translocation)
3. increased glucose storage (stimulates glycolysis (long term) glycogen synthesis
4. increases protein synthesis (stimulates expression of translation initiation complex)

Question 8

inaction in adipose

Answer 8

1. increase glucose uptake: stimulates GLUT4 translocation
2. increase glucose storage: glycolysis
3. decreased free fatty acids: lipolysis
4. triglycerides: insulin action stimulates LPL

Question 9

how does LH work in males?

in females?

Answer 9

in males: leydig cells secretes testosterone

in females: theca cells? testo is converted to estrogen by adjacent granulosa cells
also stimulates ovulation and corpus luteum? progesterone

Question 10

follicle stimulating hormone

what does it do in males and in females?

Answer 10

both sexes: supports gamete development

male: supports sertoli cells and sperm development
female: stimulates granulosa cells and follicle development

Question 11

what is the anti?mullerian hormone?

Answer 11

SRY on Y chromosome leads to testicular production of AMH
produced by sertoli cells in testes starting at 9 wks gestation
causes regression of mullerian ducts in male fetus

Question 12

what do inhibins do?

Answer 12

inhibit FSH production by pituitary
women: primordial follicles secrete inhibin B
dominant follicle secretes inhibin A

men: sertoli cells secrete inhibin B, no recognized role for inhibin A in men

Question 13

when does GnRH pulse frequency increase? when does it decrease?

Answer 13

increases with puberty, at night, at mid menstrual cycle, after menopause

decreases with starvation, illness, sex steroid feedback

(testosteron, estrogen, progesterone inhibits)

Question 14

gonadal steroids
where do they work?
are they free or bound?
what produces estrogen? testosterone?

Answer 14

gonadal steroids work mainly through nuclear receptors
98% bound to sex hormone binding globulin
testosterone: prodcued by testicular leydig cells (adrenals and ovaries)

estrogen: produced by ovaries, adrenals, and peripheral metabolism of testosterone

Question 15

what does testosterone do?

what are 2 enzymes that metabolize it?what are the byproducts?

Answer 15

stimulates embryonic development of wolffian duct organs (epididymis, vas deferens, ejaculatory duct)
metabolized to estrogen by aromatase
metabolized to dihydrotestosterone by 5?alpha reductase
DHT?? binds more strongly to androgen receptor, stimulates dvlpmnt of external genitalia, stimulates maturation at puberty

Question 16

5 functions of testosterone

Answer 16

1. promotes spermatogenesis/sperm life
2. maintains accessory organs
3. muscle growth
4. secondary sexual characteristics
5. feedback to pituitary/hypothalamus

Question 17

steps of normal male puberty (6)

Answer 17

genitals enlarge and mature
hair grows on face and body
body becomes more muscular
voice deepens
sperm are produced
growth finishes

Question 18

estrogen (3 roles)

Answer 18

promotes secondary sex characteristics (breast, fat distribution, widened pelvis, uterine growth, vaginal wall thickening and lube)

contributes to bones: close epiphyses, maintenance of bone density

important for initiation and maintenance of pregnanacy

Question 19

where is progesterone produced?

what does it do?

Answer 19

produced by corpus luteum, and after 8 wks of pregnancy is is mainly produced by placenta
stimulates endometrium to prepare for implantation
important for maintenance of pregnancy (dec uterine contractility, dec maternal immune response, inhibits lactation)

Question 20

steps of normal female puberty

Answer 20

breasts develop
pelvis, hips, thighs widen
pubic and underarm hair develop
ovarian follicles develop
menstruation starts

Question 21

definition of hypogonadism

Answer 21

inability to reproduce (loss of sex hormone secretion/function or loss of gametes)

physiologic: due to menopause, energy restriction, severe illness, aging (potentially)

Question 22

what happens to follicles as we age?

Answer 22

decline dramatically during the decade prior to menopause

Question 23

what happens during menopause?

lab values?

Answer 23

exhaustion of egg supply (loss of inhibin feedback on FSH, loss of estrogen production by developing follicles, loss of progesterone from corpus lutea)

cessation of menstruation

labs: low inhibin B, evelated FSH and LH, low estrogen and progesterone

Question 24

how does leuprolide, gosrelin, and busarelin work?

what are they used for?

Answer 24

GnRH given continuously?? suppress LH adn FSH

used to: 1. turn off” precocious puberty

Question 25

how do sex steroids work?

Answer 25

suppress LH and FSH

oral contraceptive pills

Question 26

which drugs are flutamide and nilutamide?

Answer 26

androgen receptor blockers used in prostate cancer

Question 27

which drugs are selective estrogen receptor modulators? action?

Answer 27

tomoxifen
blocks estrogen receptors
used in tx of breast cancer

Question 28

what kinds of drugs are letrozole and anastrozole? what are they used for?

Answer 28

aromatase inhibitors?? blocks conversion of testosterone to estrogen
used for breast cancer

Question 29

what kind of drug is finasteride?

Answer 29

5 alpha reductase inhibitor
blocks conversion of testosterone to DHT
sued for prostatic hypertrophy or prostate cancer

Question 30

what are examples of hypogonadism at birth?

if <12 wks?

Answer 30

hyopogonadal XY fetus
< 6 wks, no AMH?? (loss of SRY or gonadal dysgenesis)?? female mullerian internal structures persist
< 12 wks: no DHT (ineffective 5 alpha reductase or defective androgen receptor): female appearing or ambiguous sex genitals

female does not depend on ovarian hormones, so you can have normal female phenotype and you wont see issues till puberty

Question 31

what syndrome has absent GNRH?

Answer 31

kallmans syndrome: olfactory nerve fail to migrate through cribiform plate, gnRH dont migrate to hypothalamus, causing failure to initiate puberty and anosmia
presents at purberty

Question 32

which syndromes present at puberty?

Answer 32

kallmens syndrome
hypopituitarism

gonadal failure
genetic: turners XO, klinefelters XXY, hemochromatosis
autoimmune, infectious (mumps), traumatic (torsion)

Question 33

what are effects of hypogonadism in male puberty?

Answer 33

dec dvlpment of penis
small testes
dec male pattern body hair
dec muscle mass
lack of deepening voice
conintued growth w/ excessive length of arms and legs
gynecomastia

Question 34

effects of hypogonadism in female puberty

Answer 34

lack of breast development
amenorrhea and oligomenorrhea
decreased growth of pubic hair
decreased gynecoid fat deposition
continued growth with arms and legs longer than body

Question 35

major causes of adult hypogonadism
primary gonadal failure (5)
pituitary/hypothalamic (5)

Answer 35

primary:
klinefelters XXY, turners XO
gonadal injury (trauma, infeciton?mumps, high fevers, chemo, radiation)
infiltrative disease? hemochromatosis, sarcoidosis, amyloidosis
systemic disease? cirrhosis, renal failure, sickle cell, DM
autoimmune

secondary:
kallmans
pituitary disease
meds (androgenic steroids, opiates)
cranial irradiation
alcoholism

Question 36

effects of hypogonadism in adults

Answer 36

premenopausal women:
irregular/absent menses, hot flashes, dysphareunia, decreased libido, osteroporosis

men: infertility due to spermatogenesis, decreased libido, erectile dysfunction, dec muscle strength, dec lean mass, osteoporosis, dec male hair, small soft testes

Question 37

what do you test in hypogonadism?

Answer 37

test/estrogen
low estrogen twice in AM for males
last menstrual period for femals

LH/FSH: low in secondary hypogonadism, high in primary hypogonadism
(but pre?puberty? FSH/LH values are low
post menopause? FSH and LH are high
pulsatile makes values indeterminate

semen analysis (volume, concentration, motility, morphology, WBC)?? for fertility

inhibin B declines with loss of follicles or sertoli cels
anti?mullerian hormone?? indicates presnce of functional testis

Question 38

female: what lab values do you check for suspected hypogonadism?

Answer 38

hCG (rule out pregnancy), LH, FSH, estrogen, TSH, T4, prolactin (check for thyroid function)

if primary ovarian failure?? check for XO

if FSH or LH are not markedly high?? check for hyperandrogenism?? could be androgenic tumor
(polycystic ovarian syndrome)

Question 39

what are goals of hormone replacement?

Answer 39

prevention of osteoporosis, tx hot flashes, tx sexual dysfunction, maintain muscle strength and mass

Question 40

how can you restore fertility?

Answer 40

gnRH admin by subcutaneous pump?
needs to be pulsatile, requires intact pituitary
(not available in US)

LH and FSH admin by daily injection:

women: FSH and LH at midcycle to mimic menstrual cycle (monitor estrogen levels and follicle dvlpment by ultrasound)
risk: ovarian hyperstimulation

men: LH and FSH doses constant
monitor testosterone and sperm count (requires 3 months to inc sperm and testosterone)

Question 41

how do you give estrogen replacement for:
hot flashes
vaginal/GU atorphy
osteoporosis

Answer 41

hot flashes: short term E (<3 yrs)
vaginal/GGU atrophy: use vaginal E lotion with little systemic absorption
osteoporosis: very effective, but due to risk of breast cancer is out of favor
raloxifene has E agonist effect on bone, but antagonist effect on uterus

Question 42

what are risks of estrogen replacement? (6)

Answer 42

venous thromboembolism
gallbladder disease
stroke
heart disease(when given in older pt)
breast cancer
endometrial cancer (not increased with progesterone is concurrently used)

contraindicated in estrogen dependent cancer (breast, endometrial)
history of thrombotic dz
history of vascular disease, cancer

Question 43

5 benefits of testosterone

Answer 43

maintenance of 2ndary sex characterstics
inc muslce mass
inc bone density
improved energy
improved libido

ORAL testosteron NOT recommdnded (first pass hepatic metabolism can affect LFTs and lipids?? hepatoma, cholestatic jaundice)

Question 44

risks of testerone

Answer 44

CV risk
lipid alteration
erythrocytosis
fluid retention
benign prostatic hyperplasia
prostate cancer
hepatotoxicity
slepe apnea
gynecomastia
skin reactions
acne, oily skin
testicular atropy, infertility (low sperm count)