Basic question about Klinefelter's

[Phloston]

---

Members don't see this ad.

I'm caught up on this basic mechanism and need some assistance here..

In Klinefelter's, we've got decreased testosterone, increased LH, increased oestrogen and normal FSH/inhibin A, is that correct?

My confusion is regarding the exact mechanism for why oestrogen is increased considering absolute testosterone is decreased, and it is testosterone that is ultimately converted into oestrogen.

In Klinefelter's, there is Leydig cell dysfunction and decreased testosterone, but aromatase is normal because Sertoli cell function is normal. Therefore, the little testosterone that is available is aromatized to oestrogen, with the result being an increased oestrogen/testosterone ratio, rather than a mere absolute increase in oestrogen.

Is that right?

Cheers,

 

[usmlesuccess]

Yeah, I think you are correct. It is probably a relative increase. Also, you have to account for the fact that the androgens produced in the adrenal cortex are also being aromatized in the periphery. Thus, you have an excess of estrogens compared to androgens.

 

[Ilovewater]

In Klinefelter's, we've got decreased testosterone, increased LH, increased oestrogen and normal FSH/inhibin A, is that correct?

Cheers,

Actually, according to FA (unless there's a mistake):
-Seminiferous tubules dysgenesis: decreased inhibin, increased FSH
-Leydig cell dysfunction: decreased testosterone, increased LH
-Increased estrogen

 

[HelpPleaseMD]

Actually, according to FA (unless there's a mistake):
-Seminiferous tubules dysgenesis: decreased inhibin, increased FSH
-Leydig cell dysfunction: decreased testosterone, increased LH
-Increased estrogen

this is correct and the way UWORLD presents it
sometimes the LH is normal. but the FSH and is increased due to decreased inhibin

 

[Phloston]

I know FA says decreased inhibin --> increased FSH, but I had sworn I had encountered a practice question somewhere that had FSH being normal in 47XXY, and I was surprised by it. So I just want to confirm...

 

[HelpPleaseMD]

I would go with the more common presentation that was stated by Ilovewater. The test itself is really basic pholoston. Its very common presentations on very common topics asked in weird ways.

 

[thecalccobra]

Actually, according to FA (unless there's a mistake):
-Seminiferous tubules dysgenesis: decreased inhibin, increased FSH
-Leydig cell dysfunction: decreased testosterone, increased LH
-Increased estrogen

So increased FSH would lead to increased Sertoli cells which would aromatize Androstenedione produced from the adrenals resulting in increased estrogen? Am I right?

 

[thehundredthone]

Any increase in estrogen is an absolute increase in estrogen. The only way to increase the estrogen:testosterone ratio in males without an absolute increase is to somehow reduce the testosterone fraction without affecting the amount being acted on by aromatase.

So increased FSH would lead to increased Sertoli cells which would aromatize Androstenedione produced from the adrenals resulting in increased estrogen? Am I right?

Actually no.

www.ncbi.nlm.nih.gov/pmc/articles/PMC155680/?tool=pmcentrez

In the mammalian testis it's well known that aromatase is mainly localized in Leydig cells

The mechanism of increased aromatase in Klinefelter's is actually not known.
erc.endocrinology-journals.org/content/6/2/315.full.pdf

Finally, several conditions have been shown to be associated with increased conversion of androstenedione to estrone and/or testosterone to estradiol without the mechanism being defined. These include Klinefelter's syndrome (Wang et al. 1975), thyrotoxicosis (Southren et al. 1974, Olivo et al. 1975), and the use of spironolactone (Huffman & Azarnoff 1975).

 

[ChessMaster3000]

I'm caught up on this basic mechanism and need some assistance here..

In Klinefelter's, we've got decreased testosterone, increased LH, increased oestrogen and normal FSH/inhibin A, is that correct?

My confusion is regarding the exact mechanism for why oestrogen is increased considering absolute testosterone is decreased, and it is testosterone that is ultimately converted into oestrogen.

In Klinefelter's, there is Leydig cell dysfunction and decreased testosterone, but aromatase is normal because Sertoli cell function is normal. Therefore, the little testosterone that is available is aromatized to oestrogen, with the result being an increased oestrogen/testosterone ratio, rather than a mere absolute increase in oestrogen.

Is that right?

Cheers,

I came across this thread after having the same question. I think FA changed the wording slightly. Now for Klinefelter it says:

Dysgenesis of seminiferous tubules--> decreased inhibin leading to increased FSH (makes sense)
Abnormal Leydig cell fxn --> decrease testosterone leading to increased LH (makes sense) leading to increased estrogen (does NOT make sense)

How in the world does increase LH lead to increased estrogen in the setting of testicular dysfunction (both leydig and sertoli)? I tried searching whether LH perhaps increases androgen synthesis in adrenals and nothing definitive came up. The USMLE doesnt test on speculation. FA could be wrong, but I think there's a concept to be learned with regard to why LH increases estrogen.

Bottom line, Klinefelters has an increase in estrogen. But knowing why increase LH leads to that would be very helpful

 

[acciddropping]

LH activates desmolase that converts cholesterol to androstenedione in adrenal gland and testes and this androstenedione can be converted to estrogen by aromatase.

 

[ChessMaster3000]

LH activates desmolase that converts cholesterol to androstenedione in adrenal gland and testes and this androstenedione can be converted to estrogen by aromatase.

Does that conversion also happen in adrenal?

 

[acciddropping]

Does that conversion also happen in adrenal?

no, shouldn't be, i think.... my bad... that would be under ACTH control...
in FA2014, it says in men, androgens are converted to estrogen by cytochrome p450 aromataswe primarily in adipose tissues and testes.

 

[Phloston]

Wow, this thread was from forever ago.

Although the Sertoli cells are atrophic (low inhibin A --> increased FSH) and the Leydig cells are producing less testosterone (leading to increased LH), the Leydig cells can still aromatize testosterone to estrogen, thereby increasing the estrogen/testosterone ratio. Even though Sertoli cells classically aromatize testosterone, the Leydig cells have this function too, and despite their lesser testosterone production, show normal ability to aromatize. So estrogen is produced concurrent to low testosterone --> increased E/T ratio.

 

[ChessMaster3000]

Wow, this thread was from forever ago.

Although the Sertoli cells are atrophic (low inhibin A --> increased FSH) and the Leydig cells are producing less testosterone (leading to increased LH), the Leydig cells can still aromatize testosterone to estrogen, thereby increasing the estrogen/testosterone ratio. Even though Sertoli cells classically aromatize testosterone, the Leydig cells have this function too, and despite their lesser testosterone production, show normal ability to aromatize. So estrogen is produced concurrent to low testosterone --> increased E/T ratio.

I get the E/T ratio thing, but the pathophys of Klinefelter's is testicular dysfunction--so I would guess that Leydig cells are precluded from BOTH testosterone and aromatase production, unless you have read otherwise. It wouldn't make sense to have selective dysfunction of the testosterone production of Leydig cells yet have aromatase intact.

 

[PublicHealth26]

In case anyone is still looking for this answer: (According to Secrets...):

In Klinefelters, Testosterone does NOT have normal interaction with androgen receptors (the X chromosome carries genes for androgen receptors with long CAG repeats --> testosterone can't react with receptors) - It's not really known why.

This results in hypogonadism (no testosterone action).

Therefore, any unused testosterone is converted via aromatase --> estradiol (= increased estrogen, feminization).

Hope that helps.

 

[aspiringmd1015]

so youre saying testosterone is increased? if you have testicular atrophy, w/poor leydig cell function, how would testosterone increase?

 

[Transposony]

so youre saying testosterone is increased? if you have testicular atrophy, w/poor leydig cell function, how would testosterone increase?

Leydig cells become the prominent cell in testes because of atrophy of Seminiferous tubules.

Testosterone does not increase (it decreases) but it does not interact with androgen receptors.

Seminiferous tubules fibrosed → azoospermia, ↓ inhibin (no Sertoli cells) leads to ↑ FSH.

Prominent Leydig cells & ↑ FSH → ↑ aromatase synthesis → ↑ conversion of testosterone to estrogen.

Feminization due to testosterone conversion into estrogen by aromatase in Leydig cells & adipose.

Whatever little testosterone is produced, it does not interact with androgen receptors → feminization.