Mauritio
Member
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- Feb 26, 2018
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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 [28–30]"
"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.
"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 [28–30]"
"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]."
Steroidogenesis in the skin: implications for local immune functions
The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it ...
www.ncbi.nlm.nih.gov
Biochemical activity of cytochrome P450scc and P450c17 was demonstrated in SEB-1 sebocytes using radioimmunoassay."
Cytochrome P450c17: Regulation of Gene Expression and Enzyme Function at the Bifurcation in Steroid Hormone Synthesis
Cytochrome P450c17 is a member of the cytochrome P450 gene superfamily (Nebert et al. 1991) that is of special interest because of its functional significance, catalytic properties, and hormonal regulation. Located in the membranes of the smooth endoplasmic reticulum...
link.springer.com
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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