Talk:Androgen backdoor pathway/GA2

GA Review

The following discussion is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

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Reviewer: Boghog (talk · contribs) 12:30, 29 January 2024 (UTC)

GA review (see here for what the criteria are, and here for what they are not)
It is reasonably well written. a (prose, spelling, and grammar): b (MoS for lead, layout, word choice, fiction, and lists): It is factually accurate and verifiable. a (references): b (citations to reliable sources): c (OR): d (copyvio and plagiarism): It is broad in its coverage. a (major aspects): b (focused): It follows the neutral point of view policy. Fair representation without bias: It is stable. No edit wars, etc.: It is illustrated by images, where possible and appropriate. a (images are tagged and non-free images have fair use rationales): b (appropriate use with suitable captions):
Overall: Pass/Fail:
· · ·

Overview

OK, I will take this on. This is the first GAN review that I have ever done, so I am not sure how best to do this. My preference is to take several passes starting with the overall organization, then focus on details of each of the sections, and then finally the lead. The biggest challenge as I see it is is to make this highly technical article accessible to as wide an audience as possible, especially the lead.

As the previous reviewer mentioned, not all passages have been cited. More on that later. Boghog (talk) 12:30, 29 January 2024 (UTC)

Organization

The function section is actually a mix of function and history. Also there is a bit of history in the importance section. My suggestion is to move all of the history to a single section. The current history is section is specific events. It would be good to start this section a general overview of the most important develpments followed by the chronological list of specific events.

I also think having seperate function and importance sections is a bit redundant. The pathway is important because of its function. So why seperate the two?

One thing that should be emphasized is that both the cononical and backdoor pathways are required for full male sexual development. Also it is not clear what exactly is the physiological importance of the 11-oxygenated pathway. This should be clarified.

For completeness, I think the biochemistry section should be introduced by a brief section covering the canonical pathway with a

Main article: Testosterone § Biosynthesis

hatnote.

The order of the "17α-Hydroxyprogesterone pathway" and "Progesterone pathway" subsection should be flipped. As shown in figure 2, there is a subpathway that leads from progesterone to 17α-Hydroxyprogesterone so it makes sense to discuss progesterone first.

Flip the order of benign prostatic hyperplasia cancer. Hyperplasia is a precursor of cancer so it makes sense to discuss hyperplasia first.

The clinical signifance section mixes both the DHT backdoor and 11-oxygenated pathways. It would be good if possible to discuss the clinical signficance of each of the pathways seperately. Boghog (talk) 13:20, 29 January 2024 (UTC)

Sorry, I didn't notice that you left a message back than on 29 January 2024, although I am subscribed to the page "Androgen backdoor pathway". I did notice only now that that you left the message. Please give me 1 day to resolve the issues that you've identified. Thank you! Maxim Masiutin (talk) 18:05, 31 January 2024 (UTC)

I now explicitly subscribed to the page Talk:Androgen_backdoor_pathway/GA2 so I would not miss any notice you will leave here. It was probably because transcluded pages do not trigger notifications. Maxim Masiutin (talk) 18:06, 31 January 2024 (UTC)

I am now resolving the objections that you've noticed. The GA review should verify that the article formally meets the GA criteria; still, the interpretation of these criteria may vary between the reviewers; a GA article should not be as good as a FA article :-) Maxim Masiutin (talk) 11:27, 1 February 2024 (UTC)

The function of androgen backdoor pathways is to produce clinically significant androgens in situations where the conventional pathway is insufficient, such as in male fetal development.

I emphasized in the function that both the canonical and backdoor pathways are required for full male sexual development, by writing "The function of androgen backdoor pathways is to produce clinically significant androgens in normal conditions where the conventional pathway is insufficient, such as in male early sexual differentiation."

Still, the function of the backdoor pathways in 11-oxygenated androgen biosynthesis for normal healthy humans is unknown. It is known than 11-oxygenated androgens are are major circulating androgens in healthy women, but they are likely synthesized from T (T->11OHT->11KT) rather than via backdoor pathways.

I mentioned the essense of the canonical pathway ("In the canonical pathways of androgen biosynthesis, DHT is synthesized from T via 5α-reduction, so that 5α-reduction of T, a C19 steroid, is the last step of the pathway (see Dihydrotestosterone § Biosynthesis). In the backdoor pathways, to the contrary, 5α-reduction of C21 steroids is the first step").

I propose you to keep the order of "17α-Hydroxyprogesterone pathway" vs "Progesterone pathway", because 17α-Hydroxyprogesterone pathway is better studied and better characterized, with more information on the enzymes available.

You also mentioned that the clinical significance section mixes both the DHT backdoor and 11-oxygenated pathways, and suggested to discuss the clinical significance of each of the pathways seperately, still, these pathways are only activated in pathological conditions, and they are likely activated both, so DHT is synthesized via backdoor pathways with 11KDHT, therefore, it will be problematic to discuss them separately.

I flipped cancer and hyperplasia as you suggested.

Should you have further notices, please let me know. Maxim Masiutin (talk) 12:39, 1 February 2024 (UTC)

Thanks for your edits merge history into one section. That looks better.

One quick reflection on nomenclature. One needs to clearly distinquish between physiology and pathophysiology. Physiological refers to the normal functioning of an organism. Cinical (pathophysiology) refers to treating or diagnosing disease. The role of the backdoor pathway in normal sexual develop should be described as physiologically important. In contrast, a loss of function mutation in an enzyme involved in the backdoor pathway can lead to a clinically significant outcome (abnormal sexual development). My recommendation is to replace all occurrences of the word "clinically" with "physiologically", except where it is being discussed in a disease context (e.g., the clincal significance section).

Also I would appreciate if you would reconsider the order of "17α-Hydroxyprogesterone pathway" and "Progesterone pathway" sections. When I compared these two section to figure 2, I was initially confused, and I have some background in this area. If I am having trouble following it, I would imagine others will as well. It would be much clearer if the "Progesterone pathway" is discussed first because that is what occurs first in the figure. And there is a good reason for the order in the figure (there is a subpathway that leads from progesterone to 17α-hydroxyprogesterone). Because of the highly technical nature of the subject, it is doubly important to make the article as easy to follow as possible. Logical flow and consistency between the text and the figures is much more important than which section has been more throughly studied. More later. Boghog (talk) 07:11, 2 February 2024 (UTC)

OK, I swapped the order of these pathways, although it required editing, as the second pathway proceeded the same way as the first pathway after a certain point. Maxim Masiutin (talk) 18:24, 4 February 2024 (UTC)

I also replaced "clinical" to "physiological" except when it was about a disease; and made a section on biosynthesis of conventional androgens. Maxim Masiutin (talk) 16:07, 5 February 2024 (UTC)

Therefore, I hope I resolved all the issues that you've identified. The only remaining questions are about the issues you mentioned were identified in the initial review, however, I thought I already resolved them, as I made edits, for example, explained the term feedstock, etc. As for the sentence "this route may be activated regardless of age and sex by even a mild increase in circulating 17OHP levels", I don't understand why do you think that it is awkward to read. This sentence is grammatically correct. It correctly uses the phrase "regardless of" to indicate that age and sex do not affect the activation of the route, and the preposition "by" to specify what causes the activation (a mild increase in circulating steroid levels). Maxim Masiutin (talk) 16:11, 5 February 2024 (UTC)

I looked into Talk:Androgen backdoor pathway and Talk:Androgen backdoor pathway/GA2 and don't see any message from you. The GA review process is expected to be a light process, the article should just comply to GA requirements, even if there is room for improvement or the article is not good enough per se (apart from compliance to GA requirements). There are FA requirements which is a next step, they are more stringent. Because the GA process is intended to be lightweight, it is expected to complete in 7 days. Do you have any other todo if you think that the article does not yet meet the GA requirements? Maxim Masiutin (talk) 15:41, 10 February 2024 (UTC)

Thank you for splitting information into the subsections. It is always beneficial to have subsections. We may have future ideas on how to improve the article. The article is not "static" related to GA assessment, it can be further improved. Maxim Masiutin (talk) 21:15, 11 February 2024 (UTC)

Just to be clear, in addition to adding subheadings, the material was also reorganized, and the current first paragraph was copyedited. All of this is part of the GAN review. Per WP:GAN/I#R3, "if the problems are easy to resolve, you may be bold and fix them yourself." Boghog (talk) 09:05, 12 February 2024 (UTC)

Yes, I also noticed that, thank you, but didn't mention that. Maxim Masiutin (talk) 13:23, 12 February 2024 (UTC)

Hi, sorry for the delay. Thanks for the changes made above which I think are an improvement. I have a few more points on organization:

• Function section: I was bold and moved parts of the function section that are actually about function to the first paragraph. The rest of the section is not really about function. Instead the remainder of the section describes how androgen signaling works, the steps in the pathway, nomenclature, and pathology. I wasn't sure where to move it, so I temporarily moved it to a "androgen signaling" and "biocheimcal signifance" sections.
• "Development of the reproductive system" (implies normal physiology) section heading should be renamed to "Undervirilization" (denoting a pathology) or something similar. More later. Boghog (talk) 20:05, 11 February 2024 (UTC)
• The biosynthesis of 11KT and 11KDHT from intermediates of the classical pathway are well established (see for example the dark blue portion of figure 3 in PMID 31362062). Turning to the "11-Oxygenated androgen backdoor biosynthesis" and "Figure 3", it is claimed that the backdoor pathway provides a route to the 11-oxygenated androgens 11KT and 11KDHT. In the WikiJournal of Medicine Peer review 2 states ...the backdoor pathway is a pathway that only occurs under certain conditions. Although only recently discovered in humans, we now know that the 11-oxygenated androgen pathway functions in all healthy adults, and thus it is not a backdoor pathway as it does not require a specific set of conditions to operate.. This point was never really addressed in the response to peer review nor the final version of the WikiJournal of Medicinen article. It is also important to point out that the figure in the WikiJournal of Medicine article provides both canonical and backdoor routes to 11KT and 11KDHT whereas File:Backdoor-11-oxygenated.svg (figure 3) provides only the hypothetical route to 11KT and 11KDHT. Figure 3 is at best misleading, since it omits mention of the classical pathway and at worst, is original research. Is there any reliable source that supports that in either in the normal or a disease state, the backdoor pathway provides a signficant amount of 11KT and 11KDHT? Boghog (talk) 07:06, 12 February 2024 (UTC)

  On more careful inspection, Figure 3 of PMID 31362062 does support both the cananocial (from DHEA) and backdoor (from 5α-Pdiol/5α-17HP) pathways to 11KT and 11KDHT. Figure 3 of PMID 31362062 (a total of 12 structures starting from DHEA and 5α-Pdiol/5α-17HP) is a lot simpler than File:Backdoor-11-oxygenated.svg (26 structures) and easier to follow (no structures are connect by long arrows). Are there any literature supported sub pathways that are not included in Figure 3 of PMID 31362062? Boghog (talk) 10:52, 12 February 2024 (UTC)

  @Maxim Masiutin: I am getting lost with the C11-oxy backdoor pathway and we really need to simplify in order to make it suitable for a good article. File:Backdoor-11-oxygenated.svg (figure 3) is unwidlely and it needs to be replaced. The right hand side of Figure 1 of PMID 28774496 looks like a reasonable template. Also it would be helpful to have a schematic overview of the entire article. Here is a suggestion: File:Androgen backdoor schematic.svg that emphasizes the following (correct me if any of this is wrong): (1) the backdoor pathway is only relevant in embronic development, (2) the C11-oxy backdoor pathway is only relevant in certain disease states, (3) only 11KDHT and not 11KT is produced by the C11-oxy backdoor pathway, and (4) the cononical pathway can also produce C11-oxy androgens. Please let me know what you think. Boghog (talk) 20:50, 14 February 2024 (UTC)

  If you think we need a simplification, without the full specification of all steps in pathways, than "Androgen backdoor schematic.svg" should be OK except the arrow from DHT to 11KDHT which I don't understand, and I'm not sure about the (4) ("the canonical pathway can also produce C11-oxy androgens"). I never read anywehre that the canonical pathway can also produce C11-oxy androgens, since, the canonical pathway, by definition, only speaks about the production of T and DHT. The C11-oxy androgens in humans as relevant and potent androgens have only been discovered recently, therefore anything related to C11-oxy androgens cannot be called canonical, i.e. forming a canon, which is a dogma, an accepted principle or rule. The only dogma I found in the literature, or what was called a "dogma" is that testosterone is the main androgen converted to DHT in target tissues. For example, see PMID 28234803: Although the dogma that T and DHT are the dominant androgens in human beings has prevailed, this paradigm applies only to normal men. The work PMID 28774496 that you referred does not tell anything about supposed direct conversion from DHT to 11-OHDHT to 11-KDHT. Therefore, I like the table "Androgen backdoor schematic.svg", but I don't understand the arrow from DHT to 11KDHT and I am not aware of any work that supports your statement "(4) the canonical pathway can also produce C11-oxy androgens", for me this statement looks like a self-contradictory, for the reasons I mentioned before. Maxim Masiutin (talk) 23:45, 14 February 2024 (UTC)

  In addition to "(1) the backdoor pathway is only relevant in embryonic development", more pricese is that the backdoor pathway is only relevant in male sexual development during the embryonic phase, because for female development the backdoor pathway is not needed, as was shown by the people from a family with deficient genes that were needed for the backdoor pathways: women were normal and fertile, while men were infertile and had sexual organs underdeveloped (PMID 21802064.

  The backdoor pathways are important for the male sexual development not only in empryonic state, but also in minipuberty, which occurs predominantly in males around postnatal days 30–100. According to PMID 27471148, androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway.

  Therefore, you can probably update the table adding minipuberty phase to embryonic phase, and maybe clarifying that it is only important for healthy males, rather than females. In females, the backdoor pathway is only relevant in pathogenic conditions such as CAH that leads to excessive androgen production and virilization. Maxim Masiutin (talk) 00:19, 15 February 2024 (UTC)

  The intention of the simplified schematic is not to replace figure 2 & 3, but rather to supplement them with a high level overview that would be appropriate for the lead. Per your suggestion, I have updated the figure add early postnatal and male to the backdoor pathway.

  Figure 3 in PMID 31362062, dark blue section (lower lefthand side) shows A4 (which is part of the canonical pathway) as an intermediate leading to 3KT. Figure 1 in PMID 33539964, righthand side shows the biosynthesis of 11KT and 11KDHT starting from either T or A4 (although it is part of something called 11OHA4 pathway). It is not clear to me under what conditions these transformations can occur, but nevertheless, it does appear that intermediates and products of the canoncial pathway may lead to 11-oxy androgens. I have now labeled the arrow from T to 11KDHT as the 11OHA4 pathway. Boghog (talk) 09:36, 15 February 2024 (UTC)

  The reactions that you mentioned when 11-oxyandrogens are biosynthesized from A4 or T ocur in healthy women, because in women 11-oxyandrogens are primary androgens, levels of circulating 11KT in women are similar if not higher than that of T, see PMID 31390028 The 11-oxyandrogens are primary androgens in women but not in men probably because 11-oxyandrogens cannot be converted by aromatase to estrogens, and since in women aromatase is "stronger" than in men, to protect androgens from the aromatase, they are converted to 11-oxyandrogens. Still, these reactions are not "backdoor", because backdoor reactions are those that are roundabout T and A4, i.e. starting from C21 steroids (progesterone, 17-OH-progesterone) with their 5-alpha-reduction. Therefore, the reactions that you described fall outside the scope of this article. If you are interested, you can see more information at https://en.wikiversity.org/wiki/WikiJournal_of_Medicine/Alternative_androgen_pathways#11-Oxygenated_Androgen_Pathways_2 ; to be specific, let me quote: "only three are known in healthy humans. A4 is synthesized in the adrenal where it can undergo 11β-hydroxylation to yield 11OHA4, an important circulating androgen precursor, which is further transformed to 11KA4 and then 11KT (primarily outside the adrenal in peripheral tissue):

  A4 → 11OHA4 → 11KA4 → 11KT

  This route is regarded as the primary 11-oxygenated androgen pathway in healthy humans. It is thought that the T entry point also operates in normal human physiology, but much less that A4:

  T → 11OHT → 11OHA4 → 11KA4 → 11KT

  T → 11OHT → 11KT

  The diminished role of these pathways is supported by that fact that the adrenal produces significantly more 11OHA4 than OHT." -- there are references to other works that supports these claims in that peer-reviewed article.

  This is good that the table that you prepared does not replace, but augments the existing drawings. It is a very good addition, and great idea. Maxim Masiutin (talk) 12:44, 15 February 2024 (UTC)

@Maxim Masiutin: Now realizing that the 11-oxy backdoor pathway is important in healthy females (see for example Figure 3 in PMID 32203405 where 11KT levels are comparable to or exceed testosterone levels), I have added this to the File:Androgen backdoor schematic.svg. Is this schematic accurate and not leave out any important facts? Hopefully it now gives an 20,000 foot overview of the entire article. I have also edited the function section to be compatible with the schematic. Does this look OK? Of course, feel free to edit further.

I am still struggling with figure 3 (File:Backdoor-11-oxygenated.svg). One thing that would really help is if 11KT and 11KDHT were highlighted in red or some other way. These are the most important products of the pathway and since they are not at the bottom, they get lost in this complex figure. Also are all these reactions confirmed in the literature or are any hypothetical? Can anything be trimmed from the figure? Boghog (talk) 15:32, 18 February 2024 (UTC)

Can you please remove "Healthy females" from 11-oxy backdoor and add all pathologic conditions listed in 11-oxy-backdoor to backdoor to DHT?

See my message [1] where I mentioned that in healthy women 11-oxy androgens are biosythesized in short pathways mainly from A4 and T, rather than the long backdoor pathways? Apart from that, the drawing is correct. It is a very good idea to implement this drawing. Maxim Masiutin (talk) 16:58, 18 February 2024 (UTC)

The article "Androgen backdoor pathways" does not aim to cover all steroidogenic pathways to androgens, it only aims to cover pathways that are categorized as "backdoor", i.e. from C21 steroids by their 5-alpha-reduction, roundabout of T and A4. Maxim Masiutin (talk) 17:00, 18 February 2024 (UTC)

• • I took out "healthy females" from the schematic and made corresponding changes in the function. I realize the article subject is backdoor pathways, but it is also important to put things in context. That is why I think it is important to state what other pathways (canonical) contribute to the formation of DHT, 11KT, and 11KDHT. I am still struggling with figure 3 (File:Backdoor-11-oxygenated.svg) Could you at a minimum, at least highlight the structures of 11KT, and 11KDHT? Boghog (talk) 19:19, 18 February 2024 (UTC)

    I agree that we should highlight canonical pathways, but not the other pathways, such as 5-alpha-dione pathways that happen in prostate cancer, etc...

    Do you mean that I should make background of different color for 11KDHT in the Figure 3 (Backdoor-11-oxygenated.svg)? May I only highlight 11KDHT, but not 11KT, because 11KT is not believed to be biosythesized in significant quantities via the backdoor pathway. Maxim Masiutin (talk) 19:37, 18 February 2024 (UTC)

    • Yes, highlighting the structure 11KDHT with a colored background would be helpful. If 11KT is not believed to be synthesized in significant quantities by this pathway, why is 11KT even included in the diagram? If 11KT is excluded, it looks like 11OHT could also be removed. What is the major subroute to 11KDHT in this pathway? Can anything else be removed? Boghog (talk) 20:06, 18 February 2024 (UTC)

      OK, let me me remove the steroids that are not relevant to 11-oxygenate backdoor pathways. Maxim Masiutin (talk) 20:09, 18 February 2024 (UTC)

      17OHP is not specific to C11-oxy backdoor pathway. Both progesterone pathway and 17OHP pathways occur in normal fetus development, but the backdoor pathway to DHT in fetus from 17OHP is thought to be predominant, i.e. P4 → 17OHP → 17OHDHP → 5α-Pdiol → AST → 3α-diol → DHT is thought to be predominant in humans and marsupials and in rats, but in mice the predominant is thought to be P4 → 5α-DHP → AlloP5 → 5α-Pdiol → AST → 3α-diol → DHT.

      Therefore, I'd suggest you move 17OHP from "C11-oxy backdoor" to "backdoor", and add 21dF to "C11-oxy backdoor", as shown in "Backdoor-11-oxygenated.svg": the initial steroids are 11OHP4 (from P4) and 21dF (from 17OHP) in reaction catalyzed by CYP11, as shown by the arrows, which are then reduced by SRD5A1 immediately or after conversion to their C11-oxo form by HSD11.

      I didn't update the scheme yet at "Backdoor-11-oxygenated.svg", will do tomorrow.

      21dF is 21-deoxycortisol.

      I should also made friendlier captions in the svg, because now under 21dF is "4-Pregnene-11β,17α-diol-3,20-dione", probably I have to add 21-deoxycortisol, but keep that complex name in parenthesis (there is enough space) because the complex name demonstrates the structure of the steroid.

      See quote from the section that I wrote for Steroid#Naming convention: "Unsaturated carbons (generally, ones that are part of a double bond) in the steroid nucleus are indicated by changing -ane to -ene.[21] This change was traditionally done in the parent name, adding a prefix to denote the position, with or without Δ (Greek capital delta) which designates unsaturation, for example, 4-pregnene-11β,17α-diol-3,20-dione (also Δ4-pregnene-11β,17α-diol-3,20-dione) or 4-androstene-3,11,17-trione (also Δ4-androstene-3,11,17-trione)." Maxim Masiutin (talk) 00:49, 19 February 2024 (UTC)

      I made the file File:Backdoor-11-oxygenated.svg with highlighted 11KDHT and removed steroids that are not relevant to the backdoor pathway. Maxim Masiutin (talk) 03:41, 20 February 2024 (UTC)

      Thanks! That's clearer. Boghog (talk) 09:37, 20 February 2024 (UTC)

      I also modified the caption to match the diagram, quote: "The backdoor pathways from progesterone or 17α-hydroxyprogesterone to 11-ketodihydrotestosterone (rose background)...".

      This caption makes emphasis that the backdoor pathway is to 11-ketodihydrotestosterone rather than to just androgens. Maxim Masiutin (talk) 19:23, 21 February 2024 (UTC)

Previous review

There are several items in the previous GAN review that still have not been addressed. These include:

• in medical literature WP:Weasel
• by even a mild increase in circulating 17-OHP levels awkward to read.
• Clarify that canonical also means "general, ideal, and/or most common" pathway
• 'feedstock' WP:TECHNICAL, simplify

Boghog (talk) 18:18, 2 February 2024 (UTC)

In the initial version, there was simply the word "feedstock", and after the first GA review, I have added after the work feedstock the explanation "that is, a starting point, the initial substrate". Do you mean that I should delete the word "feedstock" altogether even though I added an explanation?

As for the word "canonical", it was not not defined in the initial revision, of the article, i.e. in the article that existed before the first review. After the first review, I defined it as an androgenic pathway that involves testosterone and/or androstenedione, and also denoted it as conventional. How would you like it it that I clarify that canonical also means "general, ideal, and/or most common" pathway? I women, it turned out to be not not the most common, it was just discovered first and denoted as such as to be opposed to the other other pathways. Also, after the first review, I emphasized that the backdoor pathway is an alternative to the conventional, canonical pathway. I also mentioned that "In the canonical pathways of androgen biosynthesis, DHT is synthesized from T via 5α-reduction, so that 5α-reduction of T, a C19 steroid, is the last step of the pathway (see Dihydrotestosterone § Biosynthesis). In the backdoor pathways, to the contrary, 5α-reduction of C21 steroids is the first step."

In the initial version of the article, the phrase "in medical literature" was in different context, now it was in the "History" section that described medical studies. Still, to not be classified as WP:Weasel, I removed this phrase "medical literature".

If you would like to check whether the issues from the first GA were resolved, please take a revision of the article that existed before the first GA, because I have resolved all the issues mentioned by the editor - so you will be able to figure out that the article was not the same as it was now.

I only expressed disagreement or questions with "by even a mild increase in circulating 17-OHP levels" was "awkward to read", still, I didn't understand why it was awkward to read and I didn't understand what was wrong with this sentence - that I mentioned. Maxim Masiutin (talk) 18:46, 4 February 2024 (UTC)

If you think I should merely remove the word "feedstock" and the phrase "by even a mild increase in circulating 17-OHP levels", please let me know. Maxim Masiutin (talk) 19:50, 4 February 2024 (UTC)

Please let me know whether the objection about "by even a mild increase in circulating 17-OHP levels" is critical, and whether you have other observations. If you think that it is critical, I will try to rewrite the sentence the other way. If you have ideas or suggestions on how to rewrite it, let me know. Otherwise, please let me know whether it is critical and we can keep it as is or I should change it. Maxim Masiutin (talk) 16:42, 6 February 2024 (UTC)

Hi Maxim, instead of this: "this route may be activated regardless of age and sex by even a mild increase in circulating 17OHP levels."

Consider phrasing that line like this: "even a mild increase in circulating 17-OHP levels may activate this pathway, regardless of the patient's age and sex."

This ends up reading easier for a couple of reasons. First, substituting pathway for route helps because unlike the latter word, "pathway" is not sometimes used as a verb. When dealing with long, winding sentences like this, those "is it a noun or a verb right now?" words can really trip up your readers. Secondly, the original phrasing makes it hard to understand that "a mild increase in circulating 17-OHP levels" is a single subject/concept/thing. The phrasing I suggested makes this much more clear, I think.

Hope this helps! Just-a-can-of-beans (talk) 06:10, 25 February 2024 (UTC)

Thank you very much for the suggestion, I took your version and the sentence is now indeed better. Maxim Masiutin (talk) 12:23, 25 February 2024 (UTC)

I made minor copyediting. Please let me know whether it is OK, or I should remove something. Maxim Masiutin (talk) 00:17, 25 February 2024 (UTC)

I also saw your edits, thank you! Overall, I like how now the lead and introductory sections look, this is much better than it was before. Maxim Masiutin (talk) 00:18, 25 February 2024 (UTC)

Perfectionism

I believe this page by now easily meets the criteria to be called a Good Article. I would like to request Boghog give this a Pass and grant GA status. You both can continue improving it after that is done, after all - seems like you could go for FA status with the way things are going here. Just-a-can-of-beans (talk) 06:16, 25 February 2024 (UTC)

I plead guilty to the charge of being a perfectionist ;-) I agree that the article is in pretty good shape now and will grant GA status Thanks for your hard work Maxim Masiutin in improving this article and for your comments Just-a-can-of-beans. Cheers Boghog (talk) 18:48, 25 February 2024 (UTC)

My main concerns about this submission were accessibility and organization. Given the highly technical nature of the subject, I believe the article after copyedits is now reasonably accessible. I also think the overall organization of the article has been improved so that it now flows well. The individual sections were in fairly good shape to begin with and the few rough spots have been improved through copyedits. Congratulations Maxim Masiutin on putting together this impressive article! Boghog (talk) 19:21, 25 February 2024 (UTC)

Thank you very much for all your help. My biggest proud was the initial article in the Wikijournal of Medicine where we with @Maneesh (1) summarized on steroid naming, not seen elsewhere (now this section is copied to Steroid section of Wikipedia); (2) Made a drawing of all 11-oxygenated androgen in a form not seen everywhere else, and (3) put forward a hypothesis about the role of non-classical CAH in CP/CPPS, first exposed by Dimitrakoff in 2008 but then forgotten; the biomarkers of disease control in CAH; the role of SRD5A2 in the backdoor pathway to DHT; immune response regulation.

That was a peer-reviewed article for specific audience that didn't fit the format of Wikipedia: it had to be simpler and could not contain those hypothesis. @Boghog made great contributions on making it simpler: (1) a simpler backdoor vs classic schematic to DHT; (2) Yet simmpler summary of all pathways and their health consequences in one table; (3) easy-to-understand lead and many other contributions to make the article consistent and easy to understand, yet without losing essential information. Thank you @Just-a-can-of-beans for your feedback on the overall article and for your suggestion on rewriting a sentence. Maxim Masiutin (talk) 20:03, 25 February 2024 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.