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medicine > Sexual Differentiation > Flashcards

Sexual Differentiation Flashcards

1
Q

What causes indifferent fetal gonads to differentiate into testes?

A

the product of the SRY/Tdy sex-determining gene (also blocks the expression of aromatase)

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2
Q

What happens if you block aromatase?

A

you prevent the conversion of testosterone to estrogen

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3
Q

What happens to the Wolffian ducts in the presence of testosterone?

A

they differentiate into male reproductive structures

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4
Q

What happens to Wollfian ducts in the absence of androgens or without the ability to respond to testosterone?

A

they regress and disappear

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5
Q

What happens to Mullerian ducts in the fetus?

A

they develop into female reproductive structures unless actively suppressed

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6
Q

What product of the SRY gene is responsible for reabsorption of the mullerian ducts and what cell type does it come from?

A

1) mullerian inhibiting factor (antimullerian hormone)

2) sertoli cells

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7
Q

Does testosterone stimulate the reabsorption of the mullerian ducts?

A

NO

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8
Q

What happens to a female embryo that has high testosterone levels?

A

both ducts will be retained

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9
Q

In what syndrome is high testosterone in the female usually seen and what deficiency is there?

A

1) congenital adrenal hyperplasia

2) 21 hydroxylase deficiency

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10
Q

What happens to an embryo is a teste is absent on one side?

A

the effects of testosterone are local - if the testis is absent on one side, the mullerian duct will be retained on that side

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11
Q

What happens to a male fetus that has functional testes but non-functioning testosterone receptors?

A

this means he is androgen insensitive and both sets of ducts will regress

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12
Q

By what week of development are testes obvious?

A

7 weeks

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13
Q

The structure of male external genitalia depends on what?

A

1) testosterone secreted by the fetal testis - without testosterone these structures develop into female external genitalia
2) conversion of testosterone to DHT (dihydrotestosterone) by 5a-reductase

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14
Q

What causes ambiguous genitalia in both sexes?

A

1) boys - insufficient androgens

2) excessive androgens

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15
Q

Which cells in the male makes testosterone and around what time do they start making it?

A

1) Leydig cells

2) weeks 6-8

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16
Q

What do sertoli cells produce? Around what weeks?

A

1) antimullerian hormone
2) androgen binding protein
3) weeks 9-12

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17
Q

What week of development do the external genetalia differentiate?

A

weeks 8-12

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18
Q

What hormone is required for differentiation of the male external genitalia?

A

Active 5a-reductase, which converts testosterone to dihydrotestosterone (DHT) - without DHT external genitalia will be female, regardless of the genetic, gonadal or hormonal sex

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19
Q

What is the genotype in Klinefelters Syndrome?

A

XXY

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20
Q

What pheotype is klinefelters?

A

male - presence of a Y chromosome (XXY)

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21
Q

What hormone levels are found in klinefelters?

A

1) testosterone low to normal

2) estrogen high

22
Q

What symptoms are found in klinfelters?

A

1) feminization, including gynecomastia

2) normal spermatogenesis does not occur and FSH levels are high due to abnormal Sertoli cell function

23
Q

What is androgen insensitivity?

A

testicular feminization - XY genotype with a defect in the testosterone receptor

24
Q

What is the phenotype of androgen insensitivity?

A

male pseudohermaphrodites - internal testes but females externally

25
Q

What happens to internal genitalia in males with androgen insensitivity?

A

No other internal genitalia besides testes

1) wolffian ducts don’t develop
2) mullerian ducts regress (antimullerian hormone)

26
Q

Why can breast development occur in androgen insensitive males?

A

peripheral conversion of testosterone to estradiol

27
Q

What is absent in males with androgen insensitivity?

A

axillary and pubic hair

28
Q

What is the treatment for androgen insensitivity?

A

1) testes are removed and patient is then given estrogen replacement therapy to maintain a normal female phenotype

29
Q

What is the problem in a 5alpha reductase deficiency?

A

inability to convert testosterone to DHT

30
Q

What are the consequences of 5alpha reductase deficiency?

A

1) male pseudohermaphrodites
2) differentiation of internal genitalia is normal (testosterone dependent)
3) differentiation of external genitalia are female (lack of DHT)

31
Q

What can happen during puberty of those with 5alpha reductase deficiency?

A

phenotypic females until puberty when masculinization can occur in response to rising testosterone

32
Q

What is the problem in Kallmann’s Syndrome?

A

hypothalamic hypogonadism - decreased or absent GnRH secretion

33
Q

What are the consequences of Kallmann’s syndrome?

A

1) crytorchism
2) microphallus (small penis)
3) failure to undergo puberty
4) testes are immature and no spernatozoa
5) anosmia

34
Q

What structures are normal in Kallmann’s syndrome?

A

1) wolffian duct derived structures are normal - probably due to androgen production in response to placental hCG rather than fetal LH

35
Q

What are the genetic links behind the anosmia in Kallmann’s syndrome?

A

1) X-linked: KAL1 ansomin !

2) autosomal dominant: Kal2/FGFR 1

36
Q

Does CAH affect males or females?

A

both!!!

37
Q

What happens in CAH in males?

A

1) excess androgens leads to suppression of the HP axis leading to low LH and impaired testicular function (short term)
2) long term - rapid growth spurt along with early maturation of genitals - prococious puberty

38
Q

What happens in CAH in females?

A

1) excess androgens lead to virulization

2) later effects - menstrual irregularities, excessive hair growth etc…

39
Q

Why is CAH usually present at birth in females?

A

bc of the effects on external genitalia

40
Q

What drives the secretion of LH and FSH?

A

GnRH

41
Q

What are the targets for LH and FSH?

A

1) LH –> Leydig cells

2) FSH –> sertoli cells

42
Q

What does LH and FSH do?

A

1) LH –> stimulate release of testosterone

2) FSH –> stimulates release of inhibin

43
Q

What does inhibin do?

A

acts as a feedback inhibitor of FSH - acts exclusively on gonadotrops to inhibit FSH secretion only

44
Q

what does testosterone do?

A

acts as a negative feedback regulator of LH and thus its own synthesis

45
Q

What is testosterone’s intratesticular actions?

A

to reinforce the effects of FSH on sertoli cells

46
Q

What controls early steroidgenesis?

A

placental hCG bc fetal HTP axis is underdeveloped

47
Q

What two times are leydig cells active?

A

1) in the fetus weeks 8-18

2) puberty - increase in number and activity

48
Q

What type of interactions are present bw sertoli cells and leydig cells?

A

bi-directional interactions

49
Q

What do sertoli cells do with testosterone?

A

1) can’t produce testosterone
2) have receptors for testosterone
3) have enzymes to convert testosterone to estradiol

50
Q

What is testosterone necessary for?

A

1) proper functioning of sertoli cells

2) spermatogenesis

51
Q

What is ABP?

A

it binds testosterone and serves as a carrier in sertoli cells and in the sminiferous tubules

52
Q

What levels of estrogen can men have?

A

circulating levels of estrogens can equal those as women - they are protected from feminization as long as tissue responsiveness remains normal

medicine (15 decks)

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