Possible close relationship between Dutasteride response and retinoid metabolism

General Discussion
#1

Genetic variations associated with response to dutasteride in the treatment of male subjects with androgenetic alopecia

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222533#:~:text=The%20synonymous%20single%20nucleotide%20polymorphism,associated%20with%20response%20to%20dutasteride.

DHRS9 (dehydrogenase/reductase SDR family member 9) has been identified as a 3α-hydroxysteroid dehydrogenase (3α-HSD)
DHRS9 possesses retinol dehydrogenase (RolDH) activity [32, 33], which converts retinol to retinal in retinoid acid (RA) synthesis (S6(B) Fig). Because DHRS9 can oxidize retinol that is bound to the cellular retinol-binding protein while many other RolDHs cannot [34, 35], it is regarded as a physiological enzyme [35]. Its expression changes during hair cycling in mice and increases in hair follicles of C57BL/6J mice that frequently develop dorsal skin alopecia. DHRS9 also increased in the hair follicles of patients with central centrifugal cicatricial alopecia [30]. Previous studies demonstrated that RA synthesis and the RA signalling system are related to hair growth and cycling [35, 36]. Furthermore, RA was reported to regulate bone morphogenetic protein and Wnt signalling pathways, which are involved in hair growth [37].

Rs2241057, the second most significant exonic SNP in this study, is located on CYP26B1 , which is also involved in regulation of RA level. RA is metabolized by cytochrome P450 26 family members (CYP26A1, B1, and C1) (S6(B) Fig) [38]. CYP26A1 and CYP26B1 are expressed and are RA-inducible in both reconstructed and in vivo human epidermis [39, 40], but CYP26B1 was suggested to be more effective under physiological conditions [41], CYP26B1 is able to inactivate both all- trans -RA and 9- cis -RA [42]. Additionally, we found that rs1128977 on RXRG is associated with response to dutasteride. This gene encodes retinoid X receptor-γ (RXRG), a nuclear receptor that is activated by 9- cis -RA. Taken together, these findings strongly suggest that RA metabolism and the RA signalling pathway are associated with response to dutasteride in MPHL, although mechanism of action needs to be elucidated in future studies.

Finkle is einhorn.

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#2

Didn’t understand any of that. Explain it to me like I’m retarded.

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#3

“In women when estrogen drops at a certain age, study found RA increases”

Something else to consider

#4

I don’t understand nothing😞

#5

I remember a news segment with an old lesbian get together, some even had full beards but none were bald.

She had a t shirt saying this is what old lesbians look like. Maybe RA was a component to no balding?

#6

idk, maybe PFS is more closely related to PAS not the other way around.

I’ll look at something else here for a minute. A higher hierarchy.

3Β-HSD

Noteworthy to this discussion is the pivotal role played by the enzyme 3β-HSD. The 3β-HSD isoenzymes catalyze an essential first step in the formation of all steroid hormones: sex steroids, mineralocorticoids and glucocorticoids. In addition to its role in the biosynthesis of 3β-Adiol from 5a-DHT, this nicotinamide adenine dinucleotide (NAD+)-dependent enzyme catalyzes the conversion of pregnenolone, 17α-hydroxypregnenolone, DHEA and androstenediol into their respective ketosteroids: progesterone, 17a-hydroxyprogesterone, androstenedione and testosterone (Fig. 1). The 3β-HSD isoenzymes control crucial steroid-forming reactions and are found not only in “classical” steroidogenic tissues, namely the adrenal cortex, ovary and testis, but also in a variety of peripheral target tissues, such as the breast, skin, brain and prostate. The isoenzyme Type I 3β-HSD is predominantly expressed in peripheral tissues. Type II 3β-HSD is predominantly expressed in the adrenal gland, ovary and testis.

A number of natural agents have been shown to influence 3β-HSD and/or 17β-HSD enzyme activity in various tissues. These include NAD, lithium, T3, zinc, vitamin A, olive oil and coconut oil.

The vitamin A derivatives, retinoic acids and retinol, have been reported to regulate steroid biosynthesis in steroidogenic tissues such as human glial cells, adrenal gland, ovary and testis. In adult rat Leydig cell cultures, both retinol and retinoic acid-enriched media showed a direct stimulatory effect on testosterone biosynthesis via 3β-HSD compared to control media, as measured by radioimmunoassay.18 All- trans -retinoic acid (ATRA), an active metabolite of vitamin A, has been shown to induce the expression of the 3β-HSD gene and its activity in cultured human glial cells.19 The synthetic form of this retinoid is available by prescription only as it is toxic in high doses. Both studies described above establish an integral role for vitamin A in enhancing 3β-HSD activity and steroidogenesis.

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#7

Yeah, I’ve looked for studies regarding finestride and RA but nothing comes up, would be interesting to see if its altered.

#8

Read the dark side.