Drareg
Member
- Joined
- Feb 18, 2016
- Messages
- 4,772
Im hoping this thread can be a place to discuss this enzyme, it seems we haven’t discussed it much on here, most of the research is about inhibition, I’m curious as to how we can increase it more specifically.
It converts testosterone to DHT, we have always focused on 5AR in general, we have 3 different versions of this enzyme, it may be the case that we are metabolically biased to produce more allopregnanolone for example and this could be the effect for some when we look to increase 5AR in general. Glycine for example increases 5AR-1.
@haidut have you come across anything interesting on this?
en.wikipedia.org
The enzyme is produced in many tissues in both males and females, in the reproductive tract, testes and ovaries,[1] skin, seminal vesicles, prostate, epididymis and many organs,[2] including the Nervous System.[3][4] There are three isoenzymes of 5α-reductase: steroid 5α-reductase 1, 2, and 3 (SRD5A1, SRD5A2 and SRD5A3
Somebody mentioned cistanche increases it, cistanche seems to increase a lot more than just this enzyme though, the study below breaks down the components of cistanche, one of these compounds could be more specific to 5AR-2, if anyone has better understanding of molecular shapes their effect maybe you can spot something here.
Some good tidbits in this study, touches on scalp levels of 5AR-1 and 2.
In 1974, a lack of 5α-dihydrotestosterone (5α-DHT), the most potent androgen across species except for fish, was shown to be the origin of a type of pseudohermaphrodism in which boys have female-like external genitalia. This human intersex condition is linked to a mutation in the steroid-5α-reductase type 2 (SRD5α2) gene, which usually produces an important enzyme capable of reducing the Δ4-ene of steroid C-19 and C-21 into a 5α- stereoisomer. Seeing the potential of SRD5α2 as a target for androgen synthesis, pharmaceutical companies developed 5α-reductase inhibitors (5ARIs), such as finasteride (FIN) and dutasteride (DUT) to target SRD5α2 in benign prostatic hyperplasia and androgenic alopecia. In addition to human treatment, the development of 5ARIs also enabled further research of SRD5α functions. Therefore, this review details the morphological, physiological, and molecular effects of the lack of SRD5α activity induced by both SRD5α mutations and in- hibitor exposures across species. More specifically, data highlights 1) the role of 5α-DHT in the development of male secondary sexual organs in vertebrates and sex determination in non-mammalian vertebrates, 2) the role of SRD5α1 in the synthesis of the neurosteroid allopregnanolone (ALLO) and 5α-androstane-3α,17β-diol (3α-diol), which are involved in anxiety and sexual behavior, respectively, and 3) the role of SRD5α3 in N-glycosylation. This review also features the lesser known functions of SRD5αs in steroid degradation in the uterus during pregnancy and glucocorticoid clearance in the liver. Additionally, the review describes the regulation of SRD5αs by the receptors of androgens, progesterone, estrogen, and thyroid hormones, as well as their differential DNA methylation. Factors known to be involved in their differential methylation are age, inflammation, and mental stimulation. Overall, this review helps shed light on the various essential functions of SRD5αs across species.
Through life, methylation patterns of SRD5αs can be modified. One factor that can act on SRD5αs’ methylation is age. Indeed, SRD5α2 is one of the most differentially methylated genes with age in mice and human liver (Mozhui and Pandey, 2017). In older BPH patients, SRD5α2′s promoter is more likely to be methylated in the prostate (Bechis et al., 2015; Ge et al., 2015). Moreover, those methylation patterns can be replicated in the prostate of old mice (Ge et al., 2015). Also, SRD5α1′s expression decreases with age in the hippocampus of rats, which correlates with increased methylation (Rossetti et al., 2015; Rossetti et al., 2016; Rossetti et al., 2019). A second factor that can increase methylation is inflammation linked to disease. Up to 36.5% of patients with BPH exhibit a decrease in SRD5α2 expression linked to hypermethylation of its promoter, which renders FIN therapy useless (Niu et al., 2011; Ge et al., 2015; Horning et al., 2015). This increase in methylation is connected to inflammation generated by the tumor ne- crosis factor-α (TNF-α) (Ge et al., 2015; Wang et al., 2017). Another factor leading to a change in methylation is mental health and stimu- lation. Enrichment of the environment can help decrease methylation of SRD5α1′s promoter in the hippocampus of rats (Rossetti et al., 2015; Rossetti et al., 2019), while social isolation will increase its methylation in the prefrontal cortex of mice (Araki et al., 2015). Additionally, pa- tients who went through FIN withdrawal and developed depression and anxiety problems exhibit high methylation of SRD5α2′s promoter (but not SRD5α1′s) in their cerebrospinal fluid
It converts testosterone to DHT, we have always focused on 5AR in general, we have 3 different versions of this enzyme, it may be the case that we are metabolically biased to produce more allopregnanolone for example and this could be the effect for some when we look to increase 5AR in general. Glycine for example increases 5AR-1.
@haidut have you come across anything interesting on this?
5α-Reductase - Wikipedia
Somebody mentioned cistanche increases it, cistanche seems to increase a lot more than just this enzyme though, the study below breaks down the components of cistanche, one of these compounds could be more specific to 5AR-2, if anyone has better understanding of molecular shapes their effect maybe you can spot something here.
Some good tidbits in this study, touches on scalp levels of 5AR-1 and 2.
In 1974, a lack of 5α-dihydrotestosterone (5α-DHT), the most potent androgen across species except for fish, was shown to be the origin of a type of pseudohermaphrodism in which boys have female-like external genitalia. This human intersex condition is linked to a mutation in the steroid-5α-reductase type 2 (SRD5α2) gene, which usually produces an important enzyme capable of reducing the Δ4-ene of steroid C-19 and C-21 into a 5α- stereoisomer. Seeing the potential of SRD5α2 as a target for androgen synthesis, pharmaceutical companies developed 5α-reductase inhibitors (5ARIs), such as finasteride (FIN) and dutasteride (DUT) to target SRD5α2 in benign prostatic hyperplasia and androgenic alopecia. In addition to human treatment, the development of 5ARIs also enabled further research of SRD5α functions. Therefore, this review details the morphological, physiological, and molecular effects of the lack of SRD5α activity induced by both SRD5α mutations and in- hibitor exposures across species. More specifically, data highlights 1) the role of 5α-DHT in the development of male secondary sexual organs in vertebrates and sex determination in non-mammalian vertebrates, 2) the role of SRD5α1 in the synthesis of the neurosteroid allopregnanolone (ALLO) and 5α-androstane-3α,17β-diol (3α-diol), which are involved in anxiety and sexual behavior, respectively, and 3) the role of SRD5α3 in N-glycosylation. This review also features the lesser known functions of SRD5αs in steroid degradation in the uterus during pregnancy and glucocorticoid clearance in the liver. Additionally, the review describes the regulation of SRD5αs by the receptors of androgens, progesterone, estrogen, and thyroid hormones, as well as their differential DNA methylation. Factors known to be involved in their differential methylation are age, inflammation, and mental stimulation. Overall, this review helps shed light on the various essential functions of SRD5αs across species.
Through life, methylation patterns of SRD5αs can be modified. One factor that can act on SRD5αs’ methylation is age. Indeed, SRD5α2 is one of the most differentially methylated genes with age in mice and human liver (Mozhui and Pandey, 2017). In older BPH patients, SRD5α2′s promoter is more likely to be methylated in the prostate (Bechis et al., 2015; Ge et al., 2015). Moreover, those methylation patterns can be replicated in the prostate of old mice (Ge et al., 2015). Also, SRD5α1′s expression decreases with age in the hippocampus of rats, which correlates with increased methylation (Rossetti et al., 2015; Rossetti et al., 2016; Rossetti et al., 2019). A second factor that can increase methylation is inflammation linked to disease. Up to 36.5% of patients with BPH exhibit a decrease in SRD5α2 expression linked to hypermethylation of its promoter, which renders FIN therapy useless (Niu et al., 2011; Ge et al., 2015; Horning et al., 2015). This increase in methylation is connected to inflammation generated by the tumor ne- crosis factor-α (TNF-α) (Ge et al., 2015; Wang et al., 2017). Another factor leading to a change in methylation is mental health and stimu- lation. Enrichment of the environment can help decrease methylation of SRD5α1′s promoter in the hippocampus of rats (Rossetti et al., 2015; Rossetti et al., 2019), while social isolation will increase its methylation in the prefrontal cortex of mice (Araki et al., 2015). Additionally, pa- tients who went through FIN withdrawal and developed depression and anxiety problems exhibit high methylation of SRD5α2′s promoter (but not SRD5α1′s) in their cerebrospinal fluid
