Mauritio

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Here's a collection of studies on the skin as a steroidogenic organ mainly to show that hormones like pregnenolone have a different metabolization topically, compared to orally.



"The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases"

"The concentration of cholesterol in the inner mitochondrial membrane of steroidogenic tissues is low [21], thus CYP11A1 normally works under subsaturating (limiting) cholesterol concentrations. Increased provision of cholesterol to the inner mitochondrial membrane by the action of the steroidogenic acute regulatory (StAR) protein causes a corresponding increase in the rate of pregnenolone synthesis [22, 23]. The fate of pregnenolone produced by CYP11A1 varies depending on the particular cell type or tissue, each of which contains a particular set of steroidogenic enzymes."

"There is now a wealth of information indicating that the StAR protein mediates the rate-limiting and regulated step in steroid biosynthesis, i.e. the delivery of cholesterol from the outer to the inner mitochondrial membrane [2830]"

"Furthermore, skin cells express functionally active CYP11A1 (there are also alternatively spliced isoforms of this enzyme in skin cells [54]), StAR and MLN64, and have the capability of starting the steroidogenic pathway de novo from cholesterol [54, 70]. They also express 3βHSD [71, 72] allowing the pathway to proceed with final production of glucocorticoids [73] and sex hormones [74]."

"These studies not only confirmed keratinocytic expression of 5α-reductase and 3α/βHSD but also demonstrated expression of 6α-hydroxylase, and reverse Δ4/Δ5 isomerase enzymes [80]."

" The most potent androgen, dehydrotestosterone (DHT), is mainly synthesized in peripheral tissues, including skin [74]."

"Addition of pregnenolone, progesterone and 17α-hydroxyprogesterone led to a significant rise of T levels in culture media, reflecting the activity of 3βHSD1 and 17βHSD3 on SZ95 sebocytes [93]."

"Up to half of the total circulating T is produced from skin and other peripheral organs [198]."

"5α-reductase (5αR) type 1 is the predominant isoform detected in the skin [104, 105] and more abundantly expressed in sebaceous and sweat glands [106], keratinocytes [78, 80] and dermal fibroblasts [107]. 5αR2 is detected in genital skin fibroblasts and IRSKs [107]."


Biochemical activity of cytochrome P450scc and P450c17 was demonstrated in SEB-1 sebocytes using radioimmunoassay."

So this shows two things are rate limiting for steroid synthesis: StAR and cholesterol/ cyp11a1.
Plus there is a abundance of steroidogenic enzymes In the skin . Proably why I and others feel more androgenic effects from pregnenolone via topical application .
I wonder if anybody has tried a cholesterol cream or if that even makes a difference.
This also shows that different enzymes are abundant in different skin areas . So results may vary depending on the place of application.



Another place where it might make sense to apply a pregnenolone/cholesterol cream is the thymus/ or the skin above it . As it also has steroidogenic enzyme. And is very vulnerable to cortisol/stress.
Peat has talked many times about the importance of the thymus.
Or the sweat glands as there's more 5a reductase, so maybe in the axilla is a good place.
 
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James b

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Nice. What substances do you think would be best applied around the thymus area? Progesterone/DHEA?
 
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A good way to get high cholesterol topically is to apply crude lanolin. Lanolin is very high in cholesterol.
 

Mauritio

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Nice. What substances do you think would be best applied around the thymus area? Progesterone/DHEA?
Yeah those plus pregnenolone. Although I'm not sure how much would actually reach the thymus,but there's definitely an higher chance compared to a spot that's further away .
I have also asked peat what he thinks are good spots for a topical application to increase steroid production...
A good way to get high cholesterol topically is to apply crude lanolin. Lanolin is very high in cholesterol.
Thanks !Have you tried it topically?
 
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James b

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Nice, I’ve got some lanolin oil. It’s extremely thick and viscous. I wonder if there is anything we can do to make it easier to spread/apply to the skin?
 

Inaut

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Nice, I’ve got some lanolin oil. It’s extremely thick and viscous. I wonder if there is anything we can do to make it easier to spread/apply to the skin?
I’d think you can cut it with mct oil and some EOs like orange oil or clove (Limonene or eugenol)?
 

James b

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Thanks man. Also really liking the look of this product, although the simplicity of the ingredients (and lack of any fillers) makes me more suspicious than it does relieved. Can’t always trust the honesty with these smaller suppliers, but on face value looks fantastic.

Laikou Cream Sheep Placenta Cream Contains Hyaluron Acid Aloe Vera Curacao Skin Care Australian Lanolin Oil Cream

Amazon product
 

Mauritio

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That's w
What about something like this? Just seems to be a liquid version. It lists lanolin as the only ingredient.

That's weird. If its a sfa it should be solid, unless it's a short or medium chained fatty acid.
Lanolin seems to be a waxy substance, which are long chain fatty acids like policosanols or stearic acid .
 

Mauritio

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This is for the german folks ,not much but enough to try it out. Because frankly I dont even know if this stuff absorbs... ?

Amazon product
 

Mauritio

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"The stratum corneum acts as the rate-limiting barrier to percutaneous drug absorption. Due to varying thickness of this layer at different body parts, drug penetration also varies at different sites being highest through mucous membrane and scrotal skin and least through palmo-plantar skin.[7] Stratum corneum also acts as a reservoir of topical steroid for up to 5 days. "

So applying cholesterol/lanolin at scrotum might be effective.
Also interesting that the skin saves steroid for up to 5 days . That means after some time you'd only have to dose 1 time per week. And explains why I get tolerance issues when only taking preg cream 2 times per week.
 
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Yeah those plus pregnenolone. Although I'm not sure how much would actually reach the thymus,but there's definitely an higher chance compared to a spot that's further away .
I have also asked peat what he thinks are good spots for a topical application to increase steroid production...

Thanks !Have you tried it topically?
Yes.
 

Mauritio

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Other sources mention lanolin has good absorption. In fact, testosterone is sometimes emulsified with lanolin (or lanolin plus vaseline) for topical application.
Cool ! Do you have a link for that?

And do they use some other adjuvant like vitamin E or alchohol in it or just T + lanolin?
 
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