17 hydroxylase deficiency in a male

[Northerncardinal]

Why is there ambigious genitalia in a male with 17 hydroxylase deficiency?

What's the source of androgens in a male (46XY) in utero? I thought the leydig cells in testes produce testosterone that promotes development of internal male reproductive organs. What's the contribution of adrenal cortex in development of male internal and external reprod. organs and descent of testes?

Someone please clarify. thanks

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[PowerDan]

A male lacking 17 hydroxylase would be incapable of synthesizing androgens in adrenals as well as gonads.

The steps for testosterone synthesis in the leydig cells is pretty much the same as androgen synthesis in the adrenals (with one extra step converting androstenedione to testosterone).

 

[Reperfused]

You're right that leydig cells in the testes produce testosterone. But to give it a thought, how do they do this? Where is the testosterone coming from? What are its precursors?

To produce testosterone in the testes you need its precursor androstenedione. To generate androstenedione, you need its precursor 17-hydroxyprogesterone. To generate 17-hydroxyprogesterone, you need its precursor progesterone. Progesterone is converted to 17-hydroxyprogesterone by the enzyme 17-a-Hydroxylase.... Uhoh! But this enzyme is deficient!
Sorry we can't generate enough testosterone then!

Hence, ambiguous genitalia even in males!

 

[Mad Jack]

I just had a quick chart I would draw a chart with 11, 17, and 21 under it, like so:

Mineralocorticoids Androgens
---------- 1 ----------------- 1
---------- 1 ----------------- 7
---------- 2 ----------------- 1

Turn all of the "1"s into upward facing arrows to see what is increased.

Mineralocorticoids Androgens
---------- ↑ -----------------↑
---------- ↑ -----------------7
---------- 2 -----------------↑

To think about what it's going to do in males versus females, just think about it logically. 11 and 21 hydroxylase deficiency are going to increase androgens. This will cause females to have male or ambiguous genitalia, while males end up with typical genitalia. 17 hydroxylase deficiency, on the other hand, results in less androgen production. In males, this is going to cause female or ambiguous genitalia, while in females genitalia will be normal since there isn't excess androgen being produced. Forgive the excess minus signs, SDN doesn't support redundant spaces so I had to use something as filler.

 

[Reperfused]

But the enzyme is deficient in the ovaries too. So there's less production of estrogen. Shouldn't there be underdeveloped female genitalia as well, then?

 

[Transposony]

But the enzyme is deficient in the ovaries too. So there's less production of estrogen. Shouldn't there be underdeveloped female genitalia as well, then?

You don't need estrogen for internal genitalia development in a female since it is the "default" pathway.
You only need estrogen for secondary sex characteristics to develop i.e. breast, pubic hair etc.

 

[Mad Jack]

You don't need estrogen for internal genitalia development in a female since it is the "default" pathway.
You only need estrogen for secondary sex characteristics to develop i.e. breast, pubic hair etc.

Basically this. Male genitalia happen because of Mullerian Inhibitory Factor or Anti-Mullerian Hormone (synonymous), depending on where you learned it, which obliterate the female genitalia, coupled with DHT encouraging growth of the male genitalia.

 

[Northerncardinal]

thanks guys. It's crystal clear now

 

[Reperfused]

You don't need estrogen for internal genitalia development in a female since it is the "default" pathway.
You only need estrogen for secondary sex characteristics to develop i.e. breast, pubic hair etc.

Right, thanks! I was missing out on an imp basic point.
So does that mean, in a female, 17-a-hydroxylase deficiency will show up at the time of puberty, when secondary sexual characteristics fail to develop?

 

[Transposony]

So does that mean, in a female, 17-a-hydroxylase deficiency will show up at the time of puberty, when secondary sexual characteristics fail to develop?

Yes. They might also have infantile uterus.