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Phar300 > lect 15 male contraceptive > Flashcards

lect 15 male contraceptive Flashcards

1
Q

sperm is generated from where

A

reproductive stem cells in testis specifically in seminiferous tubules

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2
Q

pathway of sperm

A

testis–>epididymis–>Vas Deferens–>urethra

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3
Q

place where sperm matures how and why

A

epididymis to acquire the ability to fertilize an oocyte. Sperm must differentiate and reduce size of its genetic material and develop a propulsion system

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4
Q

process where diploid stem cells spermatogonia become haploid spermatozoa and days that it takes place

A

spermatogenesis and 64 days

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5
Q

spermatozoa lack what

A

LH and FSH receptors

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6
Q

cells found outside the seminiferous tubule

A

leydig cells

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7
Q

LH acts on what and triggers what

A

Lh receptors of leydig cells and triggers testosterone synthesis

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8
Q

production of local testosterone is important for what maturation

A

germ cell production and maturation of germ cells into spermatozoa

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9
Q

testosterone release causes what feedback

A

feedback inhibition of LH AND GnRH

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10
Q

testosterone is also transported where

A

sertoli cells

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11
Q

concentration of testosterone in seminiferous tubules vs circulation

A

10 times higher

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12
Q

cells found inside seminiferous tubules

A

sertoli cells

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13
Q

mother cells of germ cells in men

A

sertoli cells

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14
Q

what acts on sertoli cells

A

FSH in the fsh receptors

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15
Q

synthesis of testosterone

A

cholesterol side chain cleaved by enzyme. cholesterol than modifies into pregnenolone until into testosterone

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16
Q

testosterone can be further metabolized into whaat

A

dihydrotestosterone DHT and estradiol

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17
Q

enzyme to make DHT and modification

A

5a reductase. reduction of a double bond

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18
Q

affinity of DHT on androgen receptors

A

higher affinity for androgen receptors than testosterone

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19
Q

estradiol use in men

A

production of estrogen in testis

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20
Q

human androgen receptor on which chromosome

A

X chromosome

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21
Q

what happens to androgen receptor upon ligand binding

A

receptor dimerizes upon ligand binding and interacts with androgen response elements in genome to turn on synthesis of genes that are androgen dependent

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22
Q

the presence of 5a reductase and aromatase in local tissues allows for what

A

differential expression in tissues

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23
Q

steroid pyramid

A

cholesterol>progestins>androgens>estrogens

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24
Q

testosterone target what organs mainly

A

mainly muscle, bone marrow, bone, brain

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25
Q

DHT target organs (4)

A

external genitilia, prostate, skin and hair

26
Q

stimulation of hair growth requires block of what enzyme

A

5a reductase

27
Q

estradiol target organs (3)

A

bone, brain, breast

28
Q

most direct way we can block sperm release

A

block vas deferens

29
Q

methods of male contraceptive (4)

A

condoms, vasectomy, withdrawal, hormonal

30
Q

hormonal contraceptive men

A

block cycle to prevent local testosterone for sperm production

31
Q

concentration of testosterone for spermatogenesis compared to concentration required to maintain male features

A

10 times higher for spermatogenesis

32
Q

testosterone administration contraceptive method and what is the goal

A

administrating exogenous testosterone for negative feedback, inhibiting local testosterone synthesis

administrating right amount of testosterone to enable feedback inhibition without inducing spermatogenesis
goal: block hypothalamic-pituitary axis to control testosterone levels

33
Q

what do we get from sustained dose of testosterone in rabbits expriment and what happens if we increase that dose

A

we blocked the feedback and turned of leydig cells.

middle of graph we see axis has been turned off and no germ cells at that specific concentration of exogenous circulating testosterone. plasma testosterone measure is the one from the implant.

as we keep increasing implant dose, we eventually get enough testosterone to maintain spermatogenesis

34
Q

problems with testosterone administration method

A

in species like rats and mokeys, there is less predictability in when do we get no sperm production.
too much heterogeneity.
difficult to calibrate the dose to get the right one

35
Q

what are PDS implants

A

combination of testosterone and estradiol that can completely shut off spermatogenesis by feedback inhibition.
estradiol is more potent in inhibiting sperm production by feedback inhibition.

36
Q

results of PDS implants

A

serum LH undetectable, spermatids much lowered. hormones levels not changed so no change in secondary sex characteristics

37
Q

problems with PDS method

A

hard to calibrate. takes 3 months to wipe out spermatogenesis in humans. in rats it takes 57 days

38
Q

testosterone and progestin hormonal method: androgen analog that is an androgen and progesterone receptor agonist

A

dimethandrolone undecanoate

39
Q

characteristics of dimethandrolone undecanoate benefits

A

not aromatized so no estrogenic activity

not a substrate for 5a-reductase.

reduce side effects seen in previous therapies like that of estrogen
suppresses LH and FSh

40
Q

testosterone analog that suppresses serum gonadotropins so cant act on leydig cells and sertoli

A

11beta-MNTDC

41
Q

name for no sperm production by drugs

A

azoospermia like cancer drugs

42
Q

control of meiosis method by control of retinoic acid effect on sperm

A

if we make retinoic acid is absent either from diet or chemically at certain stages of sperm development, we can block spermatogenesis, no germ cell production but be specific to testis because other tissues need retinoic acid.

retinoic acid important for sperm maturation

43
Q

drug inhibiting what enzyme in testis and liver for retinoic acid synthesis

consequence it had on mice

A

WIN 18,4666 inhibits enzyme ALDH1A

in mice only have undifferentiated spermatogonia and no germ cells

44
Q

cotton seed oil extract that suppresses sperm production and it side effects

A

gossypol. irreversible in some man and hypokalemic effect (high potassium levels)

45
Q

sperm chromatin contraceptive method

A

dna is six fold more compacted in sperm than somatic cells. altering 3d structure dna of sperm may alter its swim capacity

46
Q

drug targeting bromodomain containing proteins in sperm chromatin contraceptive method and what was the problem

A

JQ1

bromodomain containing proteins thought to be germ cell specific but is not

47
Q

inhibition of fertilizing ability contraceptive method

A

inhibiting maturation and fertilization ability of sperm in epididymis since it only takes 7-10 days compared to germ cells taking 2 months to become sperm

48
Q

immunocontraception method and problem

A

men have blood-testis barrier in testis to protect it so many things cannot get in.
Developing antibodies to sperm proteins, epididymal proteins and germ cells but method not reversible

49
Q

serum testosterone concentration throughout lifespan

A

high in fetal (for male patterning and development of specific processes and tissues)

High in neonatal (to modify sex specific features)

large increase in puberty/adult.

low pre puberty

50
Q

pulsatile concentrations of testosterone during which period

A

puberty and adulthood

51
Q

drug methods for men when decreasing testosterone levels (4) called androgen therapy

A

testosterone, DHEA, Melatonin, human growth hormone

52
Q

does androgen replacement therapy make men more fertile

A

NO, we see reduced sperm count

53
Q

athletes using androgens for what and consequences

A

increase bone mass and growth but likely become sterile

54
Q

estrogen levels affect what and how can we inhibit it

A

eating, copulation, and activity

block aromatase

55
Q

DHT levels affect what habit

A

eating

56
Q

what is linked to the temporary aggressiveness seen in adolescents

A

pulsatile changes in testosterone concentrations

57
Q

gradual decrease of testosterone over the age of 30 leads to consequences in what

A

libido, muscles, activity

58
Q

administrating testosterone in old men is only useful in what and administered how

A

androgen deficiency

administered as injection, patch, solution, or roll on

59
Q

androgen replacement therapy benefits (4)

A
  1. improve bone mass
  2. increase muscle mass and strength
  3. increase libido
  4. improve well being and mood
60
Q

androgen replacement therapy negative effects (alot)

A

1.Headaches
2.Baldness
3.strokes blood clots
4. High blood pressure
7. aggressive behaviour
10. severe acne
11. development of breasts
12. liver damage
13. enlarged prostate
14. shrinkage of testicles
nausea
bloating
reduced sperm count

Phar300 (18 decks)

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