Flashcards in Sexual Differentiation Deck (52):
What causes indifferent fetal gonads to differentiate into testes?
the product of the SRY/Tdy sex-determining gene (also blocks the expression of aromatase)
What happens if you block aromatase?
you prevent the conversion of testosterone to estrogen
What happens to the Wolffian ducts in the presence of testosterone?
they differentiate into male reproductive structures
What happens to Wollfian ducts in the absence of androgens or without the ability to respond to testosterone?
they regress and disappear
What happens to Mullerian ducts in the fetus?
they develop into female reproductive structures unless actively suppressed
What product of the SRY gene is responsible for reabsorption of the mullerian ducts and what cell type does it come from?
1) mullerian inhibiting factor (antimullerian hormone)
2) sertoli cells
Does testosterone stimulate the reabsorption of the mullerian ducts?
What happens to a female embryo that has high testosterone levels?
both ducts will be retained
In what syndrome is high testosterone in the female usually seen and what deficiency is there?
1) congenital adrenal hyperplasia
2) 21 hydroxylase deficiency
What happens to an embryo is a teste is absent on one side?
the effects of testosterone are local - if the testis is absent on one side, the mullerian duct will be retained on that side
What happens to a male fetus that has functional testes but non-functioning testosterone receptors?
this means he is androgen insensitive and both sets of ducts will regress
By what week of development are testes obvious?
The structure of male external genitalia depends on what?
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
What causes ambiguous genitalia in both sexes?
1) boys - insufficient androgens
2) excessive androgens
Which cells in the male makes testosterone and around what time do they start making it?
1) Leydig cells
2) weeks 6-8
What do sertoli cells produce? Around what weeks?
1) antimullerian hormone
2) androgen binding protein
3) weeks 9-12
What week of development do the external genetalia differentiate?
What hormone is required for differentiation of the male external genitalia?
Active 5a-reductase, which converts testosterone to dihydrotestosterone (DHT) - without DHT external genitalia will be female, regardless of the genetic, gonadal or hormonal sex
What is the genotype in Klinefelters Syndrome?
What pheotype is klinefelters?
male - presence of a Y chromosome (XXY)
What hormone levels are found in klinefelters?
1) testosterone low to normal
2) estrogen high
What symptoms are found in klinfelters?
1) feminization, including gynecomastia
2) normal spermatogenesis does not occur and FSH levels are high due to abnormal Sertoli cell function
What is androgen insensitivity?
testicular feminization - XY genotype with a defect in the testosterone receptor
What is the phenotype of androgen insensitivity?
male pseudohermaphrodites - internal testes but females externally
What happens to internal genitalia in males with androgen insensitivity?
No other internal genitalia besides testes
1) wolffian ducts don't develop
2) mullerian ducts regress (antimullerian hormone)
Why can breast development occur in androgen insensitive males?
peripheral conversion of testosterone to estradiol
What is absent in males with androgen insensitivity?
axillary and pubic hair
What is the treatment for androgen insensitivity?
1) testes are removed and patient is then given estrogen replacement therapy to maintain a normal female phenotype
What is the problem in a 5alpha reductase deficiency?
inability to convert testosterone to DHT
What are the consequences of 5alpha reductase deficiency?
1) male pseudohermaphrodites
2) differentiation of internal genitalia is normal (testosterone dependent)
3) differentiation of external genitalia are female (lack of DHT)
What can happen during puberty of those with 5alpha reductase deficiency?
phenotypic females until puberty when masculinization can occur in response to rising testosterone
What is the problem in Kallmann's Syndrome?
hypothalamic hypogonadism - decreased or absent GnRH secretion
What are the consequences of Kallmann's syndrome?
2) microphallus (small penis)
3) failure to undergo puberty
4) testes are immature and no spernatozoa
What structures are normal in Kallmann's syndrome?
1) wolffian duct derived structures are normal - probably due to androgen production in response to placental hCG rather than fetal LH
What are the genetic links behind the anosmia in Kallmann's syndrome?
1) X-linked: KAL1 ansomin !
2) autosomal dominant: Kal2/FGFR 1
Does CAH affect males or females?
What happens in CAH in males?
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
What happens in CAH in females?
1) excess androgens lead to virulization
2) later effects - menstrual irregularities, excessive hair growth etc...
Why is CAH usually present at birth in females?
bc of the effects on external genitalia
What drives the secretion of LH and FSH?
What are the targets for LH and FSH?
1) LH --> Leydig cells
2) FSH --> sertoli cells
What does LH and FSH do?
1) LH --> stimulate release of testosterone
2) FSH --> stimulates release of inhibin
What does inhibin do?
acts as a feedback inhibitor of FSH - acts exclusively on gonadotrops to inhibit FSH secretion only
what does testosterone do?
acts as a negative feedback regulator of LH and thus its own synthesis
What is testosterone's intratesticular actions?
to reinforce the effects of FSH on sertoli cells
What controls early steroidgenesis?
placental hCG bc fetal HTP axis is underdeveloped
What two times are leydig cells active?
1) in the fetus weeks 8-18
2) puberty - increase in number and activity
What type of interactions are present bw sertoli cells and leydig cells?
What do sertoli cells do with testosterone?
1) can't produce testosterone
2) have receptors for testosterone
3) have enzymes to convert testosterone to estradiol
What is testosterone necessary for?
1) proper functioning of sertoli cells
What is ABP?
it binds testosterone and serves as a carrier in sertoli cells and in the sminiferous tubules