Inhibition of polyamine synthesis alters hair follicle function and fiber composition.
The activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, two of the enzymes involved in the synthesis of the polyamines, were found to be high in follicle-rich homogenates of sheep skin, and to be responsive to the nutrition of the animal. Systemic provision of the inhibitor of ornithine decarboxylase, alpha difluoromethylornithine, markedly altered the length, diameter, and composition of the fiber, the last being accompanied by an increase in the proportion of the fiber occupied by paracortical cells and an increase in the level of mRNA encoding a cysteine-rich family of keratin proteins. The growth of wool follicles cultured in media containing alpha-difluoromethylornithine was not inhibited, even at high concentrations. In contrast, low concentrations of methylglyoxal (bis)guanylhydrazone, the inhibitor of S-adenosylmethionine decarboxylase, completely inhibited fiber growth in culture follicles. Addition of spermidine to the media overcame this inhibition but spermine had no effect. Further evidence that spermine is not required for normal follicle function was provided by incubating follicles with the specific inhibitor of spermine synthase, n-butyl-1,3-diaminopropane. This inhibitor, even at high concentrations, had no effect on fiber growth in vitro. Spermidine partially overcame the growth depression that occurred in follicles cultured in methionine-deficient media, suggesting that part of the requirement for methionine is for spermidine synthesis in the follicle. These investigations provide strong evidence that the polyamines in general , and spermidine in particular, play a major role in hair growth.
Hynd
P I
PI
Department of Animal Science, University of Adelaide Waite Campus, Glen Osmond, South Australia, Australia.
Nancarrow
M J
MJ
D012437:Adenosylmethionine Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D003470:Culture Media; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006197:Hair / Q000737:chemistry* / Q000187:drug effects / Q000254:growth & development; D018859:Hair Follicle / Q000201:enzymology / Q000502:physiology*; D007633:Keratins / Q000235:genetics; D008935:Mitoguazone / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism*; D012756:Sheep; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology
D003470:Culture Media; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D013096:Spermine; D007633:Keratins; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D008935:Mitoguazone; D013095:Spermidine; D000518:Eflornithine