harold
Established Member
- Reaction score
- 11
Hey all.
Was reading through the archives and discovered a few posts on this which made me somewhat uncomfortable since I have just recently gone hell for leather on topical minoxidil and don't want to think that I am doing something that will prevent he formation of collagen and age my face.
Anyway did a bit of reading and came across this study that was looking at minoxidil specifically as a treatment for fibrosis (which is coincidentally may be the determinant of the end game in the balding process - the part where you can't seem to stimulate any regrowth no matter how much DHT is blocked) and though I haven't really been through it all yet as its late and its pretty long and it involves concepts that are new to me I thought I would post a few excerpts.
"The synthesis of collagen is a multi-step process, involving several unique post-translational modifications essential for the stabilisation of the collagen molecule. The assembly of collagen molecules into the functional unit, the collagen fibril, is further stabilised by covalent intermolecular cross-links. Hydroxylation of lysine residues is one of the key steps in the maturation of collagen, providing specific sites for glycosylation (Kadler, 1994) and determining the chemical nature of the intermolecular cross-links (Eyre, 1987). A family of lysyl hydroxylases (LH; EC 1.14.11.4), consisting of LH1, LH2a, LH2b, and LH3, is responsible for the catalytic conversion of lysine into hydroxylysine"
OK so minoxidil "an antihypertensive drug, has been reported to reduce lysyl hydroxylase activity by decreasing the LH1 mRNA level" and diseases in which the lysl hydroxylases are defective demonstrate "how the devastating effect of disturbed hydroxylation of triple helical or telopeptide lysine residues on tissue performance." Sounds bad right? Maybe, maybe not.
Collagen can have different properties in the body (skin, tendons etc) based on the different cross-linking residues that are used to form that particular collagen. "In the allysine cross-linking route lysine is converted by lysyl oxidase (LOX) into the aldehyde allysine, whereas in the hydroxyallysine route hydroxylysine is converted into the aldehyde hydroxyallysine." Importantly "skin collagen contains predominantly allysine-derived cross-links and only minor amounts of hydroxyallysine-derived cross-links".
Now "In fibrotic disorders, which are characterised by an accumulation of collagen,"
such as male pattern baldness
" an increase in hydroxyallysine cross-linking is observed. There are strong indications that these cross-links diminish the susceptibility of collagen to proteolytic degradation and in this way contribute to the unwanted collagen accumulation in fibrosis"
"It is therefore plausible that redirecting collagen cross-linking towards the allysine route, by reducing the overhydroxylation of telopeptide lysine residues, prevents the irreversible deposition of collagen."
So they want to inhibit the hydroxylation of lysine so that the collagen formed is more "skin-like" and less scar tissue like.
"Consequently, LH2b becomes a prime target for an anti-fibrosis therapy based on decreasing hydroxyallysine cross-linking."
They then go on to look at whether minoxidil can do this job.
"n the present study we investigated the effect of minoxidil on the gene expression of each individual lysyl hydroxylase, in particular LH2b, and on the cross-linking of collagen to examine whether minoxidil indeed has the potential to decrease hydroxyallysine cross-link formation."
Basically they found it didnt work out quite as they hoped. minoxidil inhibited LH1 much more than LH2b. They did note "Striking similarities between the effect of minoxidil on collagen hydroxylation and cross-linking and the biochemical defects of EDS VI exist, which is understandable from the dominant effect of minoxidil on LH1 gene expression, being the lysyl hydroxylase that is mutated in EDS VI. A switch from HP to LP cross-linking, as seen in collagen deposited by minoxidil-treated fibroblasts, occurs in several tissues of EDS VI patients as well, including skin, bone, and tendon and is reflected in the substantial decrease in the HP : LP ratio"
EDS V1 or Ehlers–Danlos Syndrome Type VI is characterised by "skin fragility (soft hyperextensible skin with bad scarring and easy bruising)" which doesn't sound all that good really.
So is minoxidil possibly making facial skin a bit more fragile. Don't know. Obviously this collagen inhibition thing is a lot more complex than it sounds at first and frankly I am a little out of my field here.
Theres no real resolution of this question from the study but i imagine any significant effects of this kind would have shown up in oral usage. If anyone has a better understanding of these issues or more to add please do.
hh
Was reading through the archives and discovered a few posts on this which made me somewhat uncomfortable since I have just recently gone hell for leather on topical minoxidil and don't want to think that I am doing something that will prevent he formation of collagen and age my face.
Anyway did a bit of reading and came across this study that was looking at minoxidil specifically as a treatment for fibrosis (which is coincidentally may be the determinant of the end game in the balding process - the part where you can't seem to stimulate any regrowth no matter how much DHT is blocked) and though I haven't really been through it all yet as its late and its pretty long and it involves concepts that are new to me I thought I would post a few excerpts.
"The synthesis of collagen is a multi-step process, involving several unique post-translational modifications essential for the stabilisation of the collagen molecule. The assembly of collagen molecules into the functional unit, the collagen fibril, is further stabilised by covalent intermolecular cross-links. Hydroxylation of lysine residues is one of the key steps in the maturation of collagen, providing specific sites for glycosylation (Kadler, 1994) and determining the chemical nature of the intermolecular cross-links (Eyre, 1987). A family of lysyl hydroxylases (LH; EC 1.14.11.4), consisting of LH1, LH2a, LH2b, and LH3, is responsible for the catalytic conversion of lysine into hydroxylysine"
OK so minoxidil "an antihypertensive drug, has been reported to reduce lysyl hydroxylase activity by decreasing the LH1 mRNA level" and diseases in which the lysl hydroxylases are defective demonstrate "how the devastating effect of disturbed hydroxylation of triple helical or telopeptide lysine residues on tissue performance." Sounds bad right? Maybe, maybe not.
Collagen can have different properties in the body (skin, tendons etc) based on the different cross-linking residues that are used to form that particular collagen. "In the allysine cross-linking route lysine is converted by lysyl oxidase (LOX) into the aldehyde allysine, whereas in the hydroxyallysine route hydroxylysine is converted into the aldehyde hydroxyallysine." Importantly "skin collagen contains predominantly allysine-derived cross-links and only minor amounts of hydroxyallysine-derived cross-links".
Now "In fibrotic disorders, which are characterised by an accumulation of collagen,"
such as male pattern baldness
" an increase in hydroxyallysine cross-linking is observed. There are strong indications that these cross-links diminish the susceptibility of collagen to proteolytic degradation and in this way contribute to the unwanted collagen accumulation in fibrosis"
"It is therefore plausible that redirecting collagen cross-linking towards the allysine route, by reducing the overhydroxylation of telopeptide lysine residues, prevents the irreversible deposition of collagen."
So they want to inhibit the hydroxylation of lysine so that the collagen formed is more "skin-like" and less scar tissue like.
"Consequently, LH2b becomes a prime target for an anti-fibrosis therapy based on decreasing hydroxyallysine cross-linking."
They then go on to look at whether minoxidil can do this job.
"n the present study we investigated the effect of minoxidil on the gene expression of each individual lysyl hydroxylase, in particular LH2b, and on the cross-linking of collagen to examine whether minoxidil indeed has the potential to decrease hydroxyallysine cross-link formation."
Basically they found it didnt work out quite as they hoped. minoxidil inhibited LH1 much more than LH2b. They did note "Striking similarities between the effect of minoxidil on collagen hydroxylation and cross-linking and the biochemical defects of EDS VI exist, which is understandable from the dominant effect of minoxidil on LH1 gene expression, being the lysyl hydroxylase that is mutated in EDS VI. A switch from HP to LP cross-linking, as seen in collagen deposited by minoxidil-treated fibroblasts, occurs in several tissues of EDS VI patients as well, including skin, bone, and tendon and is reflected in the substantial decrease in the HP : LP ratio"
EDS V1 or Ehlers–Danlos Syndrome Type VI is characterised by "skin fragility (soft hyperextensible skin with bad scarring and easy bruising)" which doesn't sound all that good really.
So is minoxidil possibly making facial skin a bit more fragile. Don't know. Obviously this collagen inhibition thing is a lot more complex than it sounds at first and frankly I am a little out of my field here.
Theres no real resolution of this question from the study but i imagine any significant effects of this kind would have shown up in oral usage. If anyone has a better understanding of these issues or more to add please do.
hh
