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"Vitamin D3 analog stimulates hair growth in nude mice"
this is a repost. sorry if it has been in here before....
thanks to mkp!! check this sh*t out.
the name of the drug you want is Dovonex.
this is what mike says about it:
"I think nude mice make a nice test hurdle for hairgrowth drugs.Many
drugs can increase hairgrowth in normal mice but how effective do these
compounds ever end up being for treating male pattern baldness? Generally speaking..lousy.
Cyclosporin is another drug that grew hair in nude mice,not that many do
that I know of.Minoxidil also fails to grow hair in nude mice.
1'25 vit D3 is touchy:at low doses it increases hair growth,but at
higher doses it slows hair growth.You dont need a pharmacist to compound
it either since it is available as calcipotriene (snthetic 1'25vit D3) "
" Endocrinology 2002 Nov;143(11):4389-96 Related Articles, Links
Vitamin D3 analogs stimulate hair growth in nude mice.
Vegesna V, O'Kelly J, Uskokovic M, Said J, Lemp N, Saitoh T, Ikezoe T,
Binderup L, Koeffler HP.
Cedars-Sinai Medical Center/University of California Los Angeles School
of Medicine, Los Angeles, California 90048, USA.
The active form of vitamin D3 can regulate epidermal keratinization by
inducing terminal differentiation; and mice lacking the vitamin D
receptor display defects leading to postnatal alopecia. These
observations implicate the vitamin D3 pathway in regulation of hair
growth. We tested the ability of 1,25 dihydroxyvitamin D3 and its
synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu
(nude) mice exhibiting congenital alopecia. Nude mice were treated with
different vitamin D3 analogs at doses that we had previously found to be
the highest dose without inducing toxicity (hypercalcemia). The mice
were monitored for hair growth and were scored according to a defined
scale. Skin samples were taken for histological observation of hair
follicles and for extraction of RNA and protein. Vitamin D3 analogs
dramatically stimulated the hair growth of nude mice, although parental
1,25 dihydroxyvitamin D3 had no effect. Hair growth occurred in a
cyclical pattern, accompanied by formation of normal hair follicles and
increased expression of certain keratins (Ha7, Ha8, and Hb3).
* Vitamin D3 analogs seem to act on keratinocytes to initiate hair
follicle cycling and stimulate hair growth in mice that otherwise do not
grow hair.*
.
Reduction of intrafollicular apoptosis in chemotherapy-induced alopecia by topical calcitriol-analogs.
Schilli MB, Paus R, Menrad A.
Department of Dermatology, Charite, Humboldt-Universitat zu Berlin, Germany.
Chemotherapy-induced alopecia is thought to result from cytotoxic and apoptosis-related damage to the hair follicle. This study was designed to confirm whether keratinocyte apoptosis is indeed induced in growing (= anagen) hair follicles of C57 BL/6 mice after the injection of cyclophosphamide, using improved methods for histologic detection of apoptotic cells in murine skin. More importantly, we asked whether topical calcitriol-analogs are able to modulate cyclophosphamide-induced apoptosis in vivo, because there are conflicting reports on the effects of calcitriols on apoptosis in vitro. Anagen was induced in telogen mice on day 0 by depilation. Starting on day 5 post-depilation, the back skin of mice was topically treated with either 0.2 microg 1,25-dihydroxyvitamin D3, 2.0 microg calcipotriol, 0.02 microg KH 1060, or vehicle (ethanol) only. On the last day of treatment (i.e., day 9 post-depilation), all mice received 150 mg cyclophosphamide i.p. per kg as a single dose to induce alopecia, or vehicle (aqua dist.). Analysis of the treated skin by in situ-end labeling (using a modified terminal UTP nucleotide end labeling technique suitable for murine skin), by Hoechst 33342 stain, and by DNA electrophoresis on days 10 and 14, revealed the induction of massive apoptosis in cyclophosphamide-treated anagen hair bulbs, which was most prominent on day 10, whereas controls showed no follicular apoptosis. The calcitriol-pretreated groups demonstrated a significant reduction of apoptosis, with a maximal inhibition seen on day 14. This confirms that cyclophosphamide indeed induces massive keratinocyte apoptosis in anagen hair follicles, and provides evidence that topical calcitriol-analogs can suppress epithelial cell apoptosis in vivo. The mouse model employed here offers an excellent tool for dissecting the as yet poorly understood controls of keratinocyte apoptosis in situ and its pharmacologic manipulation.
PMID: 9764839
Cancer Res 1996 Oct 1;56(19):4438-43 Related Articles, Links
Topical calcitriol enhances normal hair regrowth but does not prevent chemotherapy-induced alopecia in mice.
Paus R, Schilli MB, Handjiski B, Menrad A, Henz BM, Plonka P.
Department of Dermatology, Virchow Hospital, Humboldt-Universitat zu Berlin, Germany. ralfpaus@ukrv.de
Using a murine model that mimics chemotherapy-induced alopecia (CIA) in humans particularly well, we show here that in contrast to previously reported CIA-protective effects in neonatal rats, topical calcitriol does not prevent CIA in adolescent mice but enhances the regrowth of normally pigmented hair shafts. When, prior to injecting 1 X 120 mg/kg cyclophosphamide i.p., 0.2 microg calcitriol or vehicle alone were administered topically to the back skin of C57BL/6 mice with all hair follicles in anagen, no significant macroscopic differences in the onset and severity of CIA were seen. However, hair shaft regrowth after CIA, which is often retarded and patchy, thus displaying severe and sometimes persistent pigmentation disorders, was significantly accelerated, enhanced, and qualitatively improved in test compared with control mice. Histomorphometric analysis suggests that this is related to the fact that calcitriol-pretreated follicles favor the "dystrophic catagen pathway" of response to chemical injury, ie., a follicular repair strategy allowing for the unusually fast reconstruction of a new, undamaged anagen hair bulb. Thus, it may be unrealistic to expect that topical calcitriol can prevent human CIA, but topical calcitriols may well enhance the regrowth of a normal hair coat.
PMID: 8813138
J Invest Dermatol 1994 Sep;103(3):318-22 Related Articles, Links
Biphasic effect of 1,25-dihydroxyvitamin D3 on human hair follicle growth and hair fiber production in whole-organ cultures.
Harmon CS, Nevins TD.
Preclinical Dermatology Research, Hoffmann-La Roche, Nutley, New Jersey 07110.
We have used a whole-organ culture system to investigate the effects of 1,25(OH)2D3 on human hair follicle growth and hair fiber production. Relatively low concentrations (1-10 nM) of 1,25(OH)2D3 stimulated the cumulative growth of hair follicles and hair fibers, by 52% and 36%, respectively (concentration producing 50% of the maximal response values of 0.3 nM). The initial rates of follicle and fiber growth were increased, whereas the respective growth periods were unaffected. At higher concentrations of 1,25(OH)2D3, there was a dose-dependent inhibition of both follicle and fiber growth (IC50 values of 100 nM), in part due to reduction in the growth periods. There was a marked delay between the onset of 1,25(OH)2D-induced hair follicle and hair fiber growth inhibition. Incubation of hair follicles with 100 nM 1,25(OH)2D3 resulted in a rapid, transient inhibition of DNA synthesis (55% inhibition at 24 h), followed by a gradual return to control levels at day 4. Prolonged (> 5 h), incubation in the presence of 100 nM of 1,25 (OH)2D3 was required for follicle growth inhibition to be manifest. Ro 31-7549, a selective inhibitor of protein kinase C, did not prevent 1,25(OH)2D3-induced inhibition of hair follicle growth. These data suggest that 1,25(OH)2D3 may play a physiologic role in maintaining optimal hair follicle activity, and that elevation of 1,25(OH)2D3 may inhibit hair growth in vivo.
PMID: 8077696
this is a repost. sorry if it has been in here before....
thanks to mkp!! check this sh*t out.
the name of the drug you want is Dovonex.
this is what mike says about it:
"I think nude mice make a nice test hurdle for hairgrowth drugs.Many
drugs can increase hairgrowth in normal mice but how effective do these
compounds ever end up being for treating male pattern baldness? Generally speaking..lousy.
Cyclosporin is another drug that grew hair in nude mice,not that many do
that I know of.Minoxidil also fails to grow hair in nude mice.
1'25 vit D3 is touchy:at low doses it increases hair growth,but at
higher doses it slows hair growth.You dont need a pharmacist to compound
it either since it is available as calcipotriene (snthetic 1'25vit D3) "
" Endocrinology 2002 Nov;143(11):4389-96 Related Articles, Links
Vitamin D3 analogs stimulate hair growth in nude mice.
Vegesna V, O'Kelly J, Uskokovic M, Said J, Lemp N, Saitoh T, Ikezoe T,
Binderup L, Koeffler HP.
Cedars-Sinai Medical Center/University of California Los Angeles School
of Medicine, Los Angeles, California 90048, USA.
The active form of vitamin D3 can regulate epidermal keratinization by
inducing terminal differentiation; and mice lacking the vitamin D
receptor display defects leading to postnatal alopecia. These
observations implicate the vitamin D3 pathway in regulation of hair
growth. We tested the ability of 1,25 dihydroxyvitamin D3 and its
synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu
(nude) mice exhibiting congenital alopecia. Nude mice were treated with
different vitamin D3 analogs at doses that we had previously found to be
the highest dose without inducing toxicity (hypercalcemia). The mice
were monitored for hair growth and were scored according to a defined
scale. Skin samples were taken for histological observation of hair
follicles and for extraction of RNA and protein. Vitamin D3 analogs
dramatically stimulated the hair growth of nude mice, although parental
1,25 dihydroxyvitamin D3 had no effect. Hair growth occurred in a
cyclical pattern, accompanied by formation of normal hair follicles and
increased expression of certain keratins (Ha7, Ha8, and Hb3).
* Vitamin D3 analogs seem to act on keratinocytes to initiate hair
follicle cycling and stimulate hair growth in mice that otherwise do not
grow hair.*
.
Reduction of intrafollicular apoptosis in chemotherapy-induced alopecia by topical calcitriol-analogs.
Schilli MB, Paus R, Menrad A.
Department of Dermatology, Charite, Humboldt-Universitat zu Berlin, Germany.
Chemotherapy-induced alopecia is thought to result from cytotoxic and apoptosis-related damage to the hair follicle. This study was designed to confirm whether keratinocyte apoptosis is indeed induced in growing (= anagen) hair follicles of C57 BL/6 mice after the injection of cyclophosphamide, using improved methods for histologic detection of apoptotic cells in murine skin. More importantly, we asked whether topical calcitriol-analogs are able to modulate cyclophosphamide-induced apoptosis in vivo, because there are conflicting reports on the effects of calcitriols on apoptosis in vitro. Anagen was induced in telogen mice on day 0 by depilation. Starting on day 5 post-depilation, the back skin of mice was topically treated with either 0.2 microg 1,25-dihydroxyvitamin D3, 2.0 microg calcipotriol, 0.02 microg KH 1060, or vehicle (ethanol) only. On the last day of treatment (i.e., day 9 post-depilation), all mice received 150 mg cyclophosphamide i.p. per kg as a single dose to induce alopecia, or vehicle (aqua dist.). Analysis of the treated skin by in situ-end labeling (using a modified terminal UTP nucleotide end labeling technique suitable for murine skin), by Hoechst 33342 stain, and by DNA electrophoresis on days 10 and 14, revealed the induction of massive apoptosis in cyclophosphamide-treated anagen hair bulbs, which was most prominent on day 10, whereas controls showed no follicular apoptosis. The calcitriol-pretreated groups demonstrated a significant reduction of apoptosis, with a maximal inhibition seen on day 14. This confirms that cyclophosphamide indeed induces massive keratinocyte apoptosis in anagen hair follicles, and provides evidence that topical calcitriol-analogs can suppress epithelial cell apoptosis in vivo. The mouse model employed here offers an excellent tool for dissecting the as yet poorly understood controls of keratinocyte apoptosis in situ and its pharmacologic manipulation.
PMID: 9764839
Cancer Res 1996 Oct 1;56(19):4438-43 Related Articles, Links
Topical calcitriol enhances normal hair regrowth but does not prevent chemotherapy-induced alopecia in mice.
Paus R, Schilli MB, Handjiski B, Menrad A, Henz BM, Plonka P.
Department of Dermatology, Virchow Hospital, Humboldt-Universitat zu Berlin, Germany. ralfpaus@ukrv.de
Using a murine model that mimics chemotherapy-induced alopecia (CIA) in humans particularly well, we show here that in contrast to previously reported CIA-protective effects in neonatal rats, topical calcitriol does not prevent CIA in adolescent mice but enhances the regrowth of normally pigmented hair shafts. When, prior to injecting 1 X 120 mg/kg cyclophosphamide i.p., 0.2 microg calcitriol or vehicle alone were administered topically to the back skin of C57BL/6 mice with all hair follicles in anagen, no significant macroscopic differences in the onset and severity of CIA were seen. However, hair shaft regrowth after CIA, which is often retarded and patchy, thus displaying severe and sometimes persistent pigmentation disorders, was significantly accelerated, enhanced, and qualitatively improved in test compared with control mice. Histomorphometric analysis suggests that this is related to the fact that calcitriol-pretreated follicles favor the "dystrophic catagen pathway" of response to chemical injury, ie., a follicular repair strategy allowing for the unusually fast reconstruction of a new, undamaged anagen hair bulb. Thus, it may be unrealistic to expect that topical calcitriol can prevent human CIA, but topical calcitriols may well enhance the regrowth of a normal hair coat.
PMID: 8813138
J Invest Dermatol 1994 Sep;103(3):318-22 Related Articles, Links
Biphasic effect of 1,25-dihydroxyvitamin D3 on human hair follicle growth and hair fiber production in whole-organ cultures.
Harmon CS, Nevins TD.
Preclinical Dermatology Research, Hoffmann-La Roche, Nutley, New Jersey 07110.
We have used a whole-organ culture system to investigate the effects of 1,25(OH)2D3 on human hair follicle growth and hair fiber production. Relatively low concentrations (1-10 nM) of 1,25(OH)2D3 stimulated the cumulative growth of hair follicles and hair fibers, by 52% and 36%, respectively (concentration producing 50% of the maximal response values of 0.3 nM). The initial rates of follicle and fiber growth were increased, whereas the respective growth periods were unaffected. At higher concentrations of 1,25(OH)2D3, there was a dose-dependent inhibition of both follicle and fiber growth (IC50 values of 100 nM), in part due to reduction in the growth periods. There was a marked delay between the onset of 1,25(OH)2D-induced hair follicle and hair fiber growth inhibition. Incubation of hair follicles with 100 nM 1,25(OH)2D3 resulted in a rapid, transient inhibition of DNA synthesis (55% inhibition at 24 h), followed by a gradual return to control levels at day 4. Prolonged (> 5 h), incubation in the presence of 100 nM of 1,25 (OH)2D3 was required for follicle growth inhibition to be manifest. Ro 31-7549, a selective inhibitor of protein kinase C, did not prevent 1,25(OH)2D3-induced inhibition of hair follicle growth. These data suggest that 1,25(OH)2D3 may play a physiologic role in maintaining optimal hair follicle activity, and that elevation of 1,25(OH)2D3 may inhibit hair growth in vivo.
PMID: 8077696
