namf
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Hi guys,
Quick q b4 hitting the sack. Read in Boards & Wards about somebody with liver dz who had increased peripheral conversion of androstenedione into estrogen. So your liver is failing and you increase your estrogen? Any phsio all-stars available to explain this pathophys..or did I mess some part of the q up!!??
Thank you very much!
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| mdwannabe
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Well liver actually breaks down the Estrogen..and detoxes the rest of extra stuff... But adipose tissue as well as some others have ability to convert Androsterone to Estrogen. Hince you gen increased conversion and decreased breakdown.
Remeber in Liver Failure, one of the signs is Gynecomastia in man...and the above is the reson.
I hope it helps.
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| namf
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Mdwannabe,
Thank you very much--as always, your explanation is clear and helps a lot.
I am humbled by my deficits in even the basic things once again; I must continue to ask these questions that I don't know in spite of my embarassement, or I will not learn.
My friend, it is me who is the real mdwannabe despite your name :wink:
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| mdwannabe
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I am glad to help in anyway. It is only by asking questions that we will learn anything, as well as, it is only by answering questions we shall remember what we have learned. So please do us all a big favor, keep on asking questions and answer other q's as well. Believe me, there is nothing to be embaraced about. We are all equal here, in our desire to learn and retain as much as possible.
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| namf
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Thanks a lot Mdwannabe! That's a great attitude you have  :icon_thumb:
So I was thinking about estrogen in men and women. I had some loose odds and ends:
1)in contraceptives (essentially, either estrogen or progestrone or both in high doses I suppose), something ends up happening where the woman gets pregnant because the p450 in the liver is induced by some medication or something...? Or was it some reduction in the production of a career protein for the estrogen, thereby resulting in??? Anybody have any idea what I'm vaguely groping for???
2)Thinking about men and women and the estrogen difference between them: I know the diagram from FA whereby your kidney cortex makes
sex hormones (with the help of 21-hydroxylase)--it is the same in men and women I suppose. So women also can produce estrogen in their ovaries (which layer--theca perhaps?), and that's why they develop breasts?
3)I couldn't care less for the sexual implications (believe it or not) of the following, but I'm dead serious about wanting to undersand it: if the male alcoholic destroys his liver's ability to break down the estrogen produced by aromatization and finally gets gynecomastia, doesn't the female do the same and therefore produce enhanced breast development? Or is there some negative feedback somewhere?
4)Further, what is the difference hormonally that women should have more estrogen? That is, if ovaries produce estrogen, and testes testosterone--doesn't that testosterone get changed into estradiol via aromatase--or is it that women have so very much estrogen produced by ovaries, and at the same time, the process of aromatization is only very slow???
Thanks a lot for your help! Me so confused!!!!
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| mdwannabe
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1) The most common reason would be p450 induction (ex. cimetidine) The carrier proteins are generally not affected by many drugs, it is liver failure or hypoxia due to portal HTN that can cause that.
2) It is all about the presence of higher concentrations of reductases and aromatases in differents tissues, so that DHEA and estrodione gets converted to appropriate hormones. Make sure you look over the diagrams in Kaplan endocrinology notes.
3)Think about the receptor responsiveness to estrogen, in reality since woman has been exposed to estrogen all her life the receptor expression is well controlled. Moreover, progesterone interplay has its affect as well. In men the receptors are there, never ben exposed to much of estrogen, strating to get bombarded with high levels of it...tissue responds very well.
4)Again, the concentration of enzymes and difference in their expression in both sexes is the responsible party.
Hope this helps.
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| namf
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Mdwannabe,
As always, a very helpful reply: thank you.
Regarding the 1st answer, I wanted to clarify the protein carriers of estrogen issue. As I had understood it previously, cirrhosis results in gynacomastia because the liver is no longer there to breakdown excess systemic estrogen--and the more adipose tissue you have, the more adipose you make. Now are there also some protein carriers of estrogen or the testosterone precursor of estrogen that are also underproduced with a failing liver? What are the consequences of underproducing those carriers?? Any USMLE style hi-yield points/questions you can think of regarding these carriers??
Finally, I appreciated your point about enzymes (aromatases) in female tissue being the main factor in estrogen production. But I wondered about the basic formula I have been hearing since high school: testes=testosterone in men, ovaries=estrogen in females. So are the ovaries not a significant source of estrogen production then??
Thank you very much as always
:icon_scratch: :icon_thumb: :icon_thumb:
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| mdwannabe
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Females make most of the estrogen in ovaries, just think about oophorectomy, we have to place them on estrogen replacement with progesterone, to prevent osteoporosis. They do make some in adipocytes, but mostly in ovaries. Now, thos who have extrordinary amouts of fat, will make an appreciable amout in fat cells, think of PCOD.
Men make most testosterone in testicles, and some in adrenals as well. Again all dew to presemce od aromatases and 5-alfa reductases.
In Liver failure you are missing a lot of proteins, and elevate most of carrier bound hormones, so estrogen will not be the worst problem..but they do have elevated levels of estrogen.
Most of high yield points will be found in Kaplan Endocrine section of Physio.
:-)
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| daira
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what my understanding is:
Estrogen doesnot need any proteins to be carried around in the blood. So in failing liver the decreased protein production wouldnt effect any estrogen levels. However other factors (as explained above- decreased destruction) would cause increased levels of estrogen.
Both ovaries and testis produce testosterone. Testosterone produced by ovaries is not released in the circulation (mostly) and is converted into estrogens (by aromatases). Testosterone produced by testis is released into circulation as they dont have aromatase enzyme.
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| daira
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what my understanding is:
Estrogen doesnot need any proteins to be carried around in the blood. So in failing liver the decreased protein production wouldnt effect any estrogen levels. However other factors (as explained above- decreased destruction) would cause increased levels of estrogen.
Both ovaries and testis produce testosterone. Testosterone produced by ovaries is not released in the circulation (mostly) and is converted into estrogens (by aromatases). Testosterone produced by testis is released into circulation as they dont have aromatase enzyme.
Please correct me if I am missing something.
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lout kar phir waheen aa jata hoon
baaraha tor chuka hoon jinko
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| mdwannabe
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actually testosterone produced by testis is boud by Androgen Binding Protein, made by Sertoli Cells. The plasma levels of testosterone come from adrenals..
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"Life not lived for others, is not worth living" Uncle Einstein
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