Now, development of the external genitalia
is strictly regulated and controlled by various hormonal signals.
is going to promote the formation of testosterone by Laydig cells
between days 50 and 150.
At this time, testosterone is converted by 5alpha-reductase
to the very powerful Dihydrotestosterone or DHT.
The DHT spike that occurs between days 50 and 150
is going to be what promotes the formation of male internal and external genitalia
and the appearance of it as a penis and scrotum.
A second spike in testosterone production at puberty,
not a DHT spike but just testosterone,
is what causes stereotypical male secondary sexual characteristics
to come into existence.
So expansion of the thyroid cartilage, deepening of the voice, and so forth,
will be due to that pubertal spike in testosterone.
This is also what allows the seminiferous tubules of the testis
to develop a canal or a lumen
which can then carry spermatozoa from the testis to the urethra.
Now, another thing that can happen with testosterone
is that it can be converted to estrogen by another enzyme called aromatase.
This is important in both sexes
because the placenta produces a great deal of testosterone
and it’s not uncommon for women to develop hair growth during pregnancy
if they’re getting exposed to too much testosterone from the placenta.
Increased exposure to estrogen at puberty is going to be
what drives the formation of feminine secondary sexual characteristics
such as breast development.
The proportion of testosterone and estrogen
that a person is exposed to both in the womb and at the puberty
is going to be what drives masculine or feminine development.
And it’s not uncommon for pubescent boys
who are producing a great deal of testosterone,
some of which develops into estrogen, to develop gynecomastia or breast tissue
that later regresses as the level of hormone exposure drops.
Ambiguous genitalia occur when either a clitoris in a female newborn is enlarged
or a penis in a male newborn is decreased in size with possible hypospadias.
These phenotypes appear different from the genotype.
Meaning, you can be XX, chromosomally female
but develop male sexual characteristics or XY,
genetically male but developing female secondary sexual characteristics.
There are some children who are XY with mutations that affect the production of DHT.
You’ll recall that DHT is important to signal masculine development in the womb.
In the case of these children,
they will develop in stereotypically, female looking ways until puberty
when the testosterone spike that’s produced at that time
will kick start masculine secondary structural characteristic development.
There are also female pseudohermaphrodites
who are genetically female with two X chromosomes
but have a masculine appearance
and masculine secondary sexual characteristics.
This is due to increased levels of testosterone exposure
while they’re developing in the womb.
This may be due to the aromatase enzyme being mutated
and not converting that testosterone into estrogen.
The enlarged clitoris in these people is going to resemble a penis
and the labia majora may be enlarged
and even fused to a variable degree resembling a scrotum.
However, because you need the Y chromosome and its testis-determining factor
to prevent formation of the uterine tubes, uterus,
and other internal female genitalia,
the paramesonephric ducts will still be present
and will form a rudimentary or even relatively stout uterus and oviduct.
Male pseudohermaphrodites are those who are XY in their genotype
and would otherwise develop as males but have a feminine appearance.
This is often due to mutation in the enzyme
that senses and responds to androgens, testosterone, and DHT.
In this case, the testis are small and relatively undeveloped.
They don’t descend into the scrotum
and in fact, the labioscrotal swellings often remain separate,
similar to a labia majora.
The penis will not enlarge and may appear clitoris like.
So testis-determining factor is still present.
It’s still there being produced by the Y chromosome,
so paramesonephric ducts will not form
and only a short vagina may be present developing off of the urogenital sinus.
People with this condition appear hyper-feminine
because unlike women who have receptors for both hormones,
these people have no response to testosterone of any kind
and they typically grow up as women, believe themselves to be women,
both genetically and phenotypically
and are often undiagnosed until they attempt to have children
and find that there is no uterus or oviduct present within their body.
Another cause of difficulty in sexual development is congenital adrenal hyperplasia.
This is caused by mutations and just various genes
that regulate hormone production in the adrenal gland,
specifically, the adrenal cortex.
It can be caused by conversion of cholesterol
which produces all of our hormones into sex hormones.
This can cause ambiguous genitalia in female infants
where the clitoris and other external genitalia enlarge
but no notable signs in male infants.
Precocious puberty can occur in both cases
since excessive levels of hormones are present.
Less common forms of congenital adrenal hyperplasia can actually cause excessive
but faulty sex hormone expression that results in the opposite,
ambiguous male genitalia and no immediate effects in female infants.
True hermaphrodites, those with both male and female internal genitalia
are incredibly rare in humans.
Thank you very much for your attention and I hope to see you on our next talk.