You do realize that cytochrome p450 is a term used that encompasses a large family of metabolic enzymes, of which Cyp19A1 (aromatase aka human placental estrogen synthetase), is a member of.
Of course i do which is why i said a KIND OF....that implies I am aware cyp450 is more than a singular enzyme. Its more like over 50 different enzymes that are considered cyp450(but shocker about 6 of them metabolize around 90% of drugs)..but obviously you couldnt interpret that from my posts.
Of course I realize this, it was the entire point of my post. Aromatase inhibitors are worthless here, theyre specific to the heme in cyp19A1. Of which 19-nors are not substrates.
Im giving you credit for being right. I have no issue that in this instance I that learned from you. However it's not penetrating your freaking retinas that initially there were still things I was questioning despite your mechanism. You sound like you have more then a high school diploma, so you know very well, it's common practice academic, medical, or any higher learning circles to question things and to continue discussing them if there are factors that were not addressed.
I never said they did not become aromatic in the chemical sense, as that is not within the scope of this discussion. They DO NOT AROMATIZE in the classical sense understood by members of this community. (
The population there was no one, it was a review, not a study)
you are right, they convert to estrogen through another pathway that I was not accounting for. I was definitely not thinking about the actual reaction at play. I'll admit it, I think in anatomy and physiology, not chemistry. I think about how it affects homeostasis and not how the molecule changes. So I will gladly give you credit for showing me the answer through a the chemical reaction. kudos to you sir
HOWEVER, it was a review based on an observation in a population! postmenopausal women. It literally was exploring the clinical implications within that population.In both the opening context and the clinical implications drawn in the conclusion. So let me re-word this: The population or the group of people that this was observed in, lead to a review on the underlying mechanism taking place so the clinical implications can be discussed for this group of people who may undergo treatment with said drugs.
Lastly, human placental estrogen synthetase is aromatase which is also Cyp19A1.
EXACTLY, it is an aromatase that CAN aromatize 19nors. It was an unaddressed factor. This goes against the proposed reasoning that a 19nor cannot be aromatized by a classical aromatase enzyme. I dug a little deeper and found some literature that further elaborates on how human aromatase in the presence of MENT does not create estrogen. This feeds into your point further strengthening your argument. Below you add another article that further supports this. It would have been AWESOME if you posted that earlier. This is good...this answers questions and furthers understandings.
Anyone who can read and can interpret the literature properly can see what I posted as a source was an explanation as to why AI's are not useful to combat 19-nor aromatization. As they do not undergo aromatization via the aromatase enzyme. They are isomerized via other cyp's, and then undergo enolization, and then O-demethylation, and lastly keto-enol tautomerization to yield estradiol. Tautomerization is not aromatization.
One thing is interpret literature, the next step is to analyze the holes in said literature to create a better understanding of the matter at hand. This is Evidence Based Medicine 101(AKA what people on these boards attempt to do...cite an article and give suggestions based on said research)....you have to be able to see the weakness of a paper to know how to apply it or when not to apply it and what extra evidence is needed to support the conclusion. So you may be able to interpret what you post but you obviously couldnt realize the conclusion of the paper was clinical implications in postmenopausal women...which is the population that paper was discussing.
You didnt pick up on the fact that there is literature to support cyp enzymes that can aromatize 19nors in the classical sense. You presented something, I asked for the source to read it because I thought it was interesting. And before Im done reading it you start with smart ass remarks instead of posting the article you did not to long ago.
And they do not undergo this to an equal extent to testosterone, not even close. I really like the excerpt from this article in the journal rheumatology to demonstrate how little 19-nors convert to estrogens. Nandrolone, without testosterone, causes a huge drop in estradiol, and then osteoporosis.
"An RCT of the anabolic steroid nandrolone in 21 men with idiopathic osteoporosis showed an increase in bone density after 3 months of treatment, which decreased to basal levels after 1 yr of treatment [17]. The apparent lack of benefit with nandrolone may be related to suppression of endogenous testosterone production and the inability to aromatize anabolic steroids such as nandrolone to oestradiol."
https://academic.oup.com/rheumatology/article/39/10/1055/1783830