Travis
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- Jul 14, 2016
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After viewing many studies showing how prostaglandins inhibit hair growth, I had an idea that keratin itself was likely under the control of the PPARs—the transcriptional receptors for the prostaglandins. After all, you have to take the ghost out of the machine at some point; there has to be a final mechanism for the effects of prostaglandins.
Mice genetically-engineered with no PPARγ receptor on their skin have scarring alopecia. Also, over-expressing PPARγ on the skin protect rats against hair loss. And just as you'd expect, anything that raises prostaglandins on the skin creates similar hair loss: over-expression of cyclooxygenase, over-expression of phospholipase A₂, and over-expression of interferon-γ on the skin all lead to bald mice. In addition to the well-known findings of Louis Garza, you'd be forced to conclude that hair loss is under the control primarily of prostaglandins. You could speculate on an indirect, or even physical mechanism for this; you could say that perhaps that the oils are creating hypoxia, or that prostaglandin D₂ is exerting its well-known ischemic effects—but let's not forget that prostaglandins also transcribe/repress mRNA directly. For this reason, I've decided to check to see if the keratin genes were under the control of the PPAR receptors:
Lemay, Danielle G., and Daniel H. Hwang. "Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics." Journal of lipid research (2006)
Danielle G. Lemay informs us that the PPAR response element is basically AGGTCA. This is the canonical DNA sequence that the PPAR receptors bind to, and you can expect any DNA sequences with the AGGTCA sequence to be under the control of the prostaglandin·PPAR receptors—and their heterodimers.
The European Nucleotide Database has full sequences for all forty keratin genes. I have searched all forty genes for the PPAR response element. This is a six nucleotide sequence, and as such would only be found every.. . . .
(¼)⁶ = (¹⁄₄₀₉₆)
. . . ..four thousand ninety-six base pairs, on average. Keratin genes are rarely this long, and this sequence is found multiple times in many of them—far exceeding chance. The keratins genes which have been found to include the full six nucleotide sequence, or the canonical PPAR response element, are listed below:
keratin 5
keratin 6
keratin 7
keratin 8
keratin 9
keratin 11
keratin 12
keratin 15
keratin 17
keratin 18
keratin 19
keratin 20
keratin 24
keratin 25
keratin 27
keratin 28
keratin 31
keratin 38
keratin 39
keratin 40
All off the other ones have either a the minus-one-base-pair-truncated five-nucleotide sequence (AGGTC) or the core sequence of AGGT, except for keratins 29, 30, and 33.
Wikipedia will inform you that keratins 31–40 are the hair keratins. With this in mind, you'd have to assume that skin keratins are also under the control of the PPAR receptors. This means: prostaglandins could effect keratin expression in epithelial barriers everywhere—even the lungs.
The hair follicle will continue-on with its cycle after explantation showing that it has what can be considered—although I downright hate the analogy—an internal "clock." This fact alone means that it's not under the control of steroid hormones, molecules which cannot be produced locally. The only steroids which are ever produced locally the ones immediately downstream of cholesterol (i.e. pregnenolone and progesterone). The sex hormones are produced by sex organs, and the adrenocorticoids indicate their origin by their name.
The hair cycle is almost certainly under the control of prostaglandins operating through PPARs, and perhaps modulated or interrupted by cytokines and growth factors which influence prostaglandin production. Peptide hormones such as the transforming growth factor beta (TGF-β) series are released cyclically during the hair cycle, appearing in the same order in which they're numbered. In most observations, TGF-β₂ marks the beginning of catagen. Aldosterone has been shown to upregulate this, powerfully, so should theoretically be able to disrupt the hair cycle. Indeed, shock has been shown to cause shedding. Perhaps this is why mineralcorticoids, such as hydrocortisone, will leave a bald spot when applied to the skin. The transforming growth factors go on to release create prostaglandins through the action of phospholipase A₂, connecting mineralcorticoids with PPAR and keratin.
The recent discoveries that prostaglandin E₂ will protect rats from radiation-induced alopecia, that prostaglandin F₂α stimulates the hair growth of the eyelashes, and that prostaglandin D₂ (and derivative J₂) powerfully suppress hair growth lends further credence to theidea fact that prostaglandins have a fundamental role in the hair cycle; and since they almost certainly control keratin production directly through the PPARs, they must be the essential and indivisible component. There is nothing downstream of prostaglandins, besides the transcription of keratin. What still needs to be understood is how the timing is controlled; If I were to take a guess, I would say that the cystosolic concentration of the enzyme prostaglandin D synthase changes in a way that shadows the hair cycle.
There are actually two types of prostaglandin D synthase: one cytosolic, and one blood-borne one (lipocalin-like prostaglandin D synthase). Besides kamikaze cytokines inducing phospholipase A₂ and cyclooxygenase-2, an upregulation of lipocalin-like prostaglandin D synthase could have similar effect. Louis Garza analyzed the mRNA for this enzyme, but he failed to give the PCR primer sequence in his paper. There appears to be no way of knowing whether he measured the mRNA for ptgds or L-ptgds. This is important, as these two enzymes have radically-different origins yet both produce prostaglandin D₂.
Mice genetically-engineered with no PPARγ receptor on their skin have scarring alopecia. Also, over-expressing PPARγ on the skin protect rats against hair loss. And just as you'd expect, anything that raises prostaglandins on the skin creates similar hair loss: over-expression of cyclooxygenase, over-expression of phospholipase A₂, and over-expression of interferon-γ on the skin all lead to bald mice. In addition to the well-known findings of Louis Garza, you'd be forced to conclude that hair loss is under the control primarily of prostaglandins. You could speculate on an indirect, or even physical mechanism for this; you could say that perhaps that the oils are creating hypoxia, or that prostaglandin D₂ is exerting its well-known ischemic effects—but let's not forget that prostaglandins also transcribe/repress mRNA directly. For this reason, I've decided to check to see if the keratin genes were under the control of the PPAR receptors:
Lemay, Danielle G., and Daniel H. Hwang. "Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics." Journal of lipid research (2006)
Danielle G. Lemay informs us that the PPAR response element is basically AGGTCA. This is the canonical DNA sequence that the PPAR receptors bind to, and you can expect any DNA sequences with the AGGTCA sequence to be under the control of the prostaglandin·PPAR receptors—and their heterodimers.
The European Nucleotide Database has full sequences for all forty keratin genes. I have searched all forty genes for the PPAR response element. This is a six nucleotide sequence, and as such would only be found every.. . . .
(¼)⁶ = (¹⁄₄₀₉₆)
. . . ..four thousand ninety-six base pairs, on average. Keratin genes are rarely this long, and this sequence is found multiple times in many of them—far exceeding chance. The keratins genes which have been found to include the full six nucleotide sequence, or the canonical PPAR response element, are listed below:
keratin 5
keratin 6
keratin 7
keratin 8
keratin 9
keratin 11
keratin 12
keratin 15
keratin 17
keratin 18
keratin 19
keratin 20
keratin 24
keratin 25
keratin 27
keratin 28
keratin 31
keratin 38
keratin 39
keratin 40
All off the other ones have either a the minus-one-base-pair-truncated five-nucleotide sequence (AGGTC) or the core sequence of AGGT, except for keratins 29, 30, and 33.
Wikipedia will inform you that keratins 31–40 are the hair keratins. With this in mind, you'd have to assume that skin keratins are also under the control of the PPAR receptors. This means: prostaglandins could effect keratin expression in epithelial barriers everywhere—even the lungs.
The hair follicle will continue-on with its cycle after explantation showing that it has what can be considered—although I downright hate the analogy—an internal "clock." This fact alone means that it's not under the control of steroid hormones, molecules which cannot be produced locally. The only steroids which are ever produced locally the ones immediately downstream of cholesterol (i.e. pregnenolone and progesterone). The sex hormones are produced by sex organs, and the adrenocorticoids indicate their origin by their name.
The hair cycle is almost certainly under the control of prostaglandins operating through PPARs, and perhaps modulated or interrupted by cytokines and growth factors which influence prostaglandin production. Peptide hormones such as the transforming growth factor beta (TGF-β) series are released cyclically during the hair cycle, appearing in the same order in which they're numbered. In most observations, TGF-β₂ marks the beginning of catagen. Aldosterone has been shown to upregulate this, powerfully, so should theoretically be able to disrupt the hair cycle. Indeed, shock has been shown to cause shedding. Perhaps this is why mineralcorticoids, such as hydrocortisone, will leave a bald spot when applied to the skin. The transforming growth factors go on to release create prostaglandins through the action of phospholipase A₂, connecting mineralcorticoids with PPAR and keratin.
The recent discoveries that prostaglandin E₂ will protect rats from radiation-induced alopecia, that prostaglandin F₂α stimulates the hair growth of the eyelashes, and that prostaglandin D₂ (and derivative J₂) powerfully suppress hair growth lends further credence to the
There are actually two types of prostaglandin D synthase: one cytosolic, and one blood-borne one (lipocalin-like prostaglandin D synthase). Besides kamikaze cytokines inducing phospholipase A₂ and cyclooxygenase-2, an upregulation of lipocalin-like prostaglandin D synthase could have similar effect. Louis Garza analyzed the mRNA for this enzyme, but he failed to give the PCR primer sequence in his paper. There appears to be no way of knowing whether he measured the mRNA for ptgds or L-ptgds. This is important, as these two enzymes have radically-different origins yet both produce prostaglandin D₂.
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